Purpose The prognosis of patients with hepatocellular carcinoma (HCC) and portal vein tumor thrombus (PVTT) is extremely poor, and systemic therapy is currently the mainstream treatment. This study aimed to assess the efficacy and safety of lenvatinib combined with anti–programmed cell death-1 antibodies and transcatheter arterial chemoembolization (triple therapy) in patients with HCC and PVTT.
Materials and Methods This retrospective multicenter study included patients with HCC and PVTT who received triple therapy, were aged between 18 and 75 years, classified as Child-Pugh class A or B, and had at least one measurable lesion. The overall survival (OS), progression-free survival (PFS), objective response rates, and disease control rates were analyzed to assess efficacy. Treatment-related adverse events were analyzed to assess safety profiles.
Results During a median follow-up of 11.23 months (range, 3.07 to 34.37 months), the median OS was greater than 24 months, and median PFS was 12.53 months. The 2-year OS rate was 54.9%. The objective response rate and disease control rate were 69.8% (74/106) and 84.0% (89/106), respectively; 20.8% (22/106) of the patients experienced grade 3/4 treatment-related adverse events and no treatment-related deaths occurred. The conversion rate to liver resection was 31.1% (33/106), with manageable postoperative complications. The median OS was not reached in the surgery group, but was 19.08 months in the non-surgery group. The median PFS in the surgery and non-surgery groups were 20.50 and 9.00 months, respectively.
Conclusion Triple therapy showed promising survival benefits and high response rates in patients with HCC and PVTT, with manageable adverse effects.
Youjin Kim, Bhumsuk Keam, Eun Joo Kang, Jin-Soo Kim, Hye Ryun Kim, Keun-Wook Lee, Jung Hye Kwon, Kyoung Eun Lee, Yaewon Yang, Yoon Hee Choi, Min Kyoung Kim, Jun Ho Ji, Tak Yun, Moon Young Choi, Ki Hyeong Lee, Sung-Bae Kim, Myung-Ju Ahn
Cancer Res Treat. 2024;56(4):1068-1076. Published online April 15, 2024
Purpose In this study, we evaluated 66 patients diagnosed with adenoid cystic carcinoma (ACC) enrolled in two Korean Cancer Study Group trials to investigate the response and progression patterns in recurrent and/or metastatic ACC treated with vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKIs).
Materials and Methods We evaluated 66 patients diagnosed with ACC who were enrolled in the Korean Cancer Study Group trials. The tumor measurements, clinical data, treatment outcomes, and progression patterns of therapy were analyzed.
Results In the 66 patients (53 receiving axitinib and 13 receiving nintedanib), the disease control rate was 61%, and three patients achieved partial response. The median follow-up, median progression-free survival (PFS), overall survival, and 6-month PFS rate were 27.6%, 12.4%, and 18.1% months and 62.1%, respectively. Among 42 patients who experienced progression, 27 (64.3%) showed target lesion progression. Bone metastasis was an independent poor prognostic factor.
Conclusion Overall, most patients demonstrated stable disease with prolonged PFS; however, prominent target lesion progression occurred in some patients. Thus, PFS may capture VEGFR-TKI efficacy better than the objective response rate.
Purpose In patients with epidermal growth factor receptor (EGFR)-mutant non–small cell lung cancer (NSCLC), EGFR tyrosine kinase inhibitors (TKIs) improve response rate and survival. However, most patients eventually develop resistance. This study aimed to identify the role of CD73 in EGFR-mutant NSCLC and explore whether CD73 inhibition may serve as a therapeutic strategy in NSCLC patients with acquired resistance to EGFR-TKIs.
Materials and Methods We evaluated the prognostic role of CD73 expression in EGFR-mutant NSCLC using tumor samples from a single institution. We silenced CD73 in EGFR-TKI–resistant cell lines using short hairpin RNA (shRNA) targeting CD73 and also transfected a vector alone as a negative control. Using these cell lines, cell proliferation and viability assays, immunoblot assays, cell cycle analysis, colony-forming assays, flow cytometry, and apoptosis analysis were performed.
Results High expression of CD73 was associated with shorter survival in patients with metastatic EGFR-mutant NSCLC treated with first-generation EGFR-TKI. CD73 inhibition synergistically inhibited cell viability with first-generation EGFR-TKI treatment compared with the negative control. When CD73 inhibition and EGFR-TKI treatment were combined, G0/G1 cell cycle arrest was induced through the regulation of p21 and cyclin D1. In addition, the apoptosis rate was increased in CD73 shRNA-transfected cells treated with EGFR-TKI.
Conclusion High expression of CD73 adversely affects the survival of patients with EGFR-mutant NSCLC. The study demonstrated that inhibiting CD73 in EGFR-TKI–resistant cell lines resulted in increased apoptosis and cell cycle arrest, which overcame the acquired resistance to first-generation EGFR-TKIs. Further research is needed to determine whether blocking CD73 plays a therapeutic role in EGFR-TKI–resistant patients with EGFR-mutant NSCLC.
Citations
Citations to this article as recorded by
Simultaneous blockade of the CD73/EGFR axis inhibits tumor growth Keivan Ardeshiri, Hadi Hassannia, Ghasem Ghalamfarsa, Hanieh Jafary, Farhad Jadidi IUBMB Life.2025;[Epub] CrossRef
Comprehensive pan-cancer analysis of CD73: Explore its association with prognosis and tumor immune microenvironment Chen Chen, Sasa Liu, Yanfen Ma Heliyon.2024; 10(22): e40329. CrossRef
Purpose We aimed to evaluate whether the addition of pemetrexed is effective in improving progression-free survival (PFS) in epidermal growth factor receptor (EGFR)–mutated patients with or without concomitant alterations.
Materials and Methods This multicenter clinical trial was conducted in China from June 15, 2018, to May 31, 2019. A total of 92 non–small cell lung cancer (NSCLC) patients harboring EGFR-sensitive mutations were included and divided into concomitant and non-concomitant groups. Patients in each group were randomly treated with EGFR–tyrosine kinase inhibitor (TKI) monotherapy or EGFR-TKI combined with pemetrexed in a ratio of 1:1. PFS was recorded as the primary endpoint.
Results The overall median PFS of this cohort was 10.1 months. There were no significant differences in PFS between patients with and without concomitant and between patients received TKI monotherapy and TKI combined with pemetrexed (p=0.210 and p=0.085, respectively). Stratification analysis indicated that patients received TKI monotherapy had a significantly longer PFS in non-concomitant group than that in concomitant group (p=0.002). In concomitant group, patients received TKI combined with pemetrexed had a significantly longer PFS than patients received TKI monotherapy (p=0.013). Molecular dynamic analysis showed rapidly emerging EGFR T790M in patients received TKI monotherapy. EGFR mutation abundance decreased in patients received TKI combined chemotherapy, which supports better efficacy for a TKI combined chemotherapy as compared to TKI monotherapy. A good correlation between therapeutic efficacy and a change in circulating tumor DNA (ctDNA) status was found in 66% of patients, supporting the guiding role of ctDNA minimal residual disease (MRD) in NSCLC treatment.
Conclusion EGFR-TKI monotherapy is applicable to EGFR-sensitive patients without concomitant alterations, while a TKI combined chemotherapy is applicable to EGFR-sensitive patients with concomitant alterations. CtDNA MRD may be a potential biomarker for predicting therapeutic efficacy.
Citations
Citations to this article as recorded by
SP3-induced Timeless transcription contributes to cell growth of lung adenocarcinoma cells Ping Tian, Dajun Du, Li Yang, Nan Zhou, Ling Tao, Divijendra Natha Reddy Sirigiri PLOS ONE.2024; 19(2): e0298295. CrossRef
PIK3CA mutation as an acquired resistance driver to EGFR-TKIs in non-small cell lung cancer: Clinical challenges and opportunities Xiaohong Liu, Wuxuan Mei, Pengfei Zhang, Changchun Zeng Pharmacological Research.2024; 202: 107123. CrossRef
Risk factors for interstitial lung disease in patients with non-small cell lung cancer with epidermal growth factor receptor-tyrosine kinase inhibitors: A systematic review and meta-analysis Yosuke Fukuda, Yoshitaka Uchida, Koichi Ando, Ryo Manabe, Akihiko Tanaka, Hironori Sagara Respiratory Investigation.2024; 62(3): 481. CrossRef
Concomitant genomic features stratify prognosis to patients with advanced EGFR mutant lung cancer Xiao Liang, Jiali Xu, Yuqin Jiang, Yuqian Yan, Hongshuai Wu, Jiali Dai, Yanan Cui, Chen Zhang, Wei Chen, Zhihong Zhang, Renhua Guo Molecular Carcinogenesis.2024; 63(9): 1643. CrossRef
Identification and Application of Emerging Biomarkers in Treatment of Non-Small-Cell Lung Cancer: Systematic Review Juan Carlos Restrepo, Darly Martínez Guevara, Andrés Pareja López, John Fernando Montenegro Palacios, Yamil Liscano Cancers.2024; 16(13): 2338. CrossRef
Purpose This study aimed to explore the impact of ABL1–tyrosine kinase inhibitors (TKIs) adherence on the survival of chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) children and clarify the potential predictors of patients’ prognosis from TKIs intake practices.
Materials and Methods Ninety newly diagnosed Ph+ ALL patients who received TKIs were enrolled. We collected the baseline characteristics and adverse events in all children; moreover, TKIs adherence was measured by an eight-item Morisky medication adherence scale (MMAS-8). Progression-free survival (PFS) and overall survival (OS) analysis were performed, and risk factors for PFS and OS were evaluated.
Results Among all patients, 69 cases were regarded as adherers, while 21 were non-adherers. The median duration of TKIs interruption was significantly prolonged in the non-adherence group than in the adherence group (13 [0-101] vs. 56 [11-128], p < 0.001). Additionally, dose reduction occurred in 55.2% of non-adherers versus 23.0% of adherers (p=0.002). The PFS and OS in adherers were significantly higher versus non-adherers (p=0.020 and p=0.039). MMAS-8 score was an independent risk factor for PFS (p=0.010) and OS (p=0.031). Among non-adherers, the median OS was only 23.1% (4.2%-42%) in patients aged ≤ 10 years versus 54.4% (38.8%-70%) in adolescents. Most of the patients who experienced TKIs non-adherence suffered pancytopenia.
Conclusion TKIs adherence during treatment significantly influenced the survival of pediatric Ph+ ALL patients, and non-adherers with age ≤ 10 years were more vulnerable to TKIs disruption. The cumulative TKIs dose should be especially emphasized to patients with age ≤ 10 years, which may result in an inferior achievement of relevant treatment milestones.
Purpose
The aim of this study was to investigate the efficacy of various epidermal growth factor receptor (EGFR)–tyrosine kinase inhibitors (TKIs) plus bevacizumab in advanced EGFR-mutant lung adenocarcinoma patients.
Materials and Methods
From August 2016 to October 2020, we enrolled advanced lung adenocarcinoma patients harboring exon 19 deletion or L858R receiving gefitinib, erlotinib and afatinib plus bevacizumab as the first-line treatment for the purposes of analysis.
Results
A total of 36 patients were included in the final analysis. Three patients received gefitinib, 17 received erlotinib, and 16 received afatinib combined with bevacizumab as the first-line treatment. The objective response rate was 77.8%, and disease control rate was 94.4%. The overall median progression-free survival (PFS) was 16.4 months, while the median PFS was 17.1 months in patients with exon 19 deletion, and 16.2 months in patients with L858R mutation (p=0.311). Regarding the use of different EGFR-TKIs, the median PFS was 17.1 months in the erlotinib group and 21.6 months in the afatinib group (p=0.617). In patients with brain metastasis at baseline, the median PFS was 18.9 months in the erlotinib group and 16.4 months in the afatinib group (p=0.747). Amongst patients harboring exon 19 deletion, the median PFS was 16.2 months in the erlotinib group and not-reached in the afatinib group (p=0.141). In patients with L858R mutation, the median PFS was 18.9 months in the erlotinib group and 16.2 months in the afatinib group (p=0.481).
Conclusion
Our research demonstrates that not only erlotinib combined with bevacizumab, but also afatinib plus bevacizumab as first-line treatment, provides solid clinical efficacy in advanced EGFR-mutant lung adenocarcinoma patients.
Citations
Citations to this article as recorded by
Clinical outcome of bevacizumab or ramucirumab combined with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors as the first line therapy in susceptible EGFR‐mutated advanced non‐small‐cell lung Chia‐Yu Kuo, Ming‐Ju Tsai, Jen‐Yu Hung, Mei‐Hsuan Lee, Kuan‐Li Wu, Yu‐Chen Tsai, Cheng‐Hao Chuang, Chung‐Wen Huang, Chin‐Ling Chen, Chih‐Jen Yang, Inn‐Wen Chong The Kaohsiung Journal of Medical Sciences.2024; 40(5): 467. CrossRef
Scorpiones, Scolopendra and Gekko Inhibit Lung Cancer Growth and Metastasis by Ameliorating Hypoxic Tumor Microenvironment via PI3K/AKT/mTOR/HIF-1α Signaling Pathway Qi-yuan Mao, Xue-qian Wang, Fei Lin, Ming-wei Yu, Hui-ting Fan, Qi Zheng, Lan-chun Liu, Chu-chu Zhang, Dao-rui Li, Hong-sheng Lin Chinese Journal of Integrative Medicine.2024; 30(9): 799. CrossRef
Real-world clinical efficacy of bevacizumab biosimilar in patients with advanced non-small-cell lung cancer Wei-Fan Ou, Kuo-Hsuan Hsu, Jeng-Sen Tseng, Po-Hsin Lee, Kun-Chieh Chen, Yen-Hsiang Huang, Gee-Chen Chang, Tsung-Ying Yang Therapeutic Advances in Medical Oncology.2024;[Epub] CrossRef
Bevacizumab plus erlotinib versus erlotinib alone for advanced EGFR-mutant non-small cell lung cancer: a meta-analysis of randomized clinical trials Ruijian Li, Weiyi Li, Fang Zhang, Shanshan Li European Journal of Medical Research.2023;[Epub] CrossRef
Bevacizumab versus Ramucirumab in EGFR-Mutated Metastatic Non-Small-Cell Lung Cancer Patients: A Real-World Observational Study Wen-Chien Cheng, Yi-Cheng Shen, Chieh-Lung Chen, Wei-Chih Liao, Chia-Hung Chen, Hung-Jen Chen, Chih-Yen Tu, Te-Chun Hsia Cancers.2023; 15(3): 642. CrossRef
Comprehensive analysis of prediction of the EGFR mutation and subtypes based on the spinal metastasis from primary lung adenocarcinoma Ran Cao, Huanhuan Chen, Huan Wang, Yan Wang, E-Nuo Cui, Wenyan Jiang Frontiers in Oncology.2023;[Epub] CrossRef
When to add anti-angiogenesis drugs to EGFR-mutated metastatic non–small cell lung cancer patients: a real-world study from Taiwan Chieh-Lung Chen, Sing-Ting Wang, Wei-Chih Liao, Chia-Hung Chen, Chih-Yen Tu, Hung-Jen Chen, Te-Chun Hsia, Wen-Chien Cheng BMC Cancer.2022;[Epub] CrossRef
State-of-the-Art Molecular Oncology of Lung Cancer in Taiwan Yung-Hung Luo, Kung-Hao Liang, Hsu-Ching Huang, Chia-I Shen, Chi-Lu Chiang, Mong-Lien Wang, Shih-Hwa Chiou, Yuh-Min Chen International Journal of Molecular Sciences.2022; 23(13): 7037. CrossRef
Comparison of afatinib and erlotinib combined with bevacizumab in untreated stage IIIB/IV epidermal growth factor receptor-mutated lung adenocarcinoma patients: a multicenter clinical analysis study Suey-Haur Lee, Yu-Ching Lin, Li-Chung Chiu, Jia-Shiuan Ju, Pi-Hung Tung, Allen Chung-Cheng Huang, Shih-Hong Li, Yueh-Fu Fang, Chih-Hung Chen, Scott Chih-Hsi Kuo, Chin-Chou Wang, Cheng-Ta Yang, Ping-Chih Hsu Therapeutic Advances in Medical Oncology.2022;[Epub] CrossRef
The efficacy and tolerability of combining pemetrexed-based chemotherapy with gefitinib in the first-line treatment of non-small cell lung cancer with mutated EGFR: A pooled analysis of randomized clinical trials Bi-Cheng Wang, Wen-Xuan Zhang, Bo-Hua Kuang, Guo-He Lin, Alessandro Rizzo PLOS ONE.2022; 17(10): e0275919. CrossRef
The non-small cell lung cancer with activating epidermal growth factor receptor (EGFR) mutation eventually acquires resistant to either first or second-generation EGFR tyrosine kinase inhibitor (TKI). As the following option, targeting EGFR T790M with third-generation EGFR TKI is now established as a standard treatment option. In this study, we are reporting the first case of resistance mechanism to the novel third-generation EGFR TKI, lazertinib, which showed promising clinical efficacy in phase 1-2 study. The patients showed resistance to the treatment by acquiring the additional EGFR C797S mutation in cis which is also confirmed from the patient-derived cell lines.
Citations
Citations to this article as recorded by
Research Advances of Small Molecule EGFR-TKIs in NSCLC 亚南 胡 Pharmacy Information.2024; 13(01): 1. CrossRef
An assessment of EGFR and HER2 inhibitors with structure activity relationship of fused pyrimidine derivatives for breast cancer: a brief review Prasad Sanjay Dhiwar, Gurubasavaraja Swamy Purawarga Matada, Rohit Pal, Ekta Singh, Abhishek Ghara, Lalmohan Maji, Sindhuja Sengupta, Ganesh Andhale Journal of Biomolecular Structure and Dynamics.2024; 42(3): 1564. CrossRef
The efficacy of almonertinib and anlotinib combination therapy for advanced non‐small‐cell lung cancer patients who continued to experience cancer progression during third‐generation EGFR‐TKI treatment: a retrospective study Yu Zhang, Chengmeng Wang, Jing Zhao, Meng Wang Thoracic Cancer.2024; 15(23): 1757. CrossRef
Successful treatment of a patient with advanced lung adenocarcinoma (EGFR-T790M and C797S cis) with lazertinib: A case report and literature review Yue Fang, Qiankun Zhang, Weimin Wang, Juanjuan Tong, Xialin Li Frontiers in Oncology.2023;[Epub] CrossRef
A Review on Fused Pyrimidine Systems as EGFR Inhibitors and Their Structure–Activity Relationship Tanuja T. Yadav, Gulam Moin Shaikh, Maushmi S. Kumar, Meena Chintamaneni, Mayur YC Frontiers in Chemistry.2022;[Epub] CrossRef
Structural Basis for Inhibition of Mutant EGFR with Lazertinib (YH25448) David E. Heppner, Florian Wittlinger, Tyler S. Beyett, Tatiana Shaurova, Daniel A. Urul, Brian Buckley, Calvin D. Pham, Ilse K. Schaeffner, Bo Yang, Blessing C. Ogboo, Earl W. May, Erik M. Schaefer, Michael J. Eck, Stefan A. Laufer, Pamela A. Hershberger ACS Medicinal Chemistry Letters.2022; 13(12): 1856. CrossRef
Potentiating Therapeutic Effects of Epidermal Growth Factor Receptor Inhibition in Triple-Negative Breast Cancer Kyu Sic You, Yong Weon Yi, Jeonghee Cho, Jeong-Soo Park, Yeon-Sun Seong Pharmaceuticals.2021; 14(6): 589. CrossRef
Paired analysis of tumor mutation burden calculated by targeted deep sequencing panel and whole exome sequencing in non-small cell lung cancer Sehhoon Park, Chung Lee, Bo Mi Ku, Minjae Kim, Woong-Yang Park, Nayoung K. D. Kim, Myung-Ju Ahn BMB Reports.2021; 54(7): 386. CrossRef
Purpose
Pyrotinib is a newly-developed irreversible pan-ErbB receptor tyrosine kinase inhibitor. This study reported the first real-world data of pyrotinib-based therapy in metastatic human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC), focusing on efficacy in lapatinib-treated patients and in brain metastasis.
Materials and Methods
One hundred thirteen patients with metastatic HER2-positive BC treated with pyrotinib-based therapy in Fudan University Shanghai Cancer Center under non-clinical trial settings from September 1, 2018 to March 1, 2019 were included.
Results
Over half patients have received more than two lines of systematic therapy and exposed to two or more kinds of anti-HER2 agents. Most patients received a combined therapy, commonly of pyrotinib plus capecitabine, or vinorelbine or trastuzumab. Median progression-free survival (PFS) was 6.3 months (range, 5.54 to 7.06 months) and objective response rate (ORR) was 29.5%, with two patients (1.9%) achieving complete response. Lapatinib-naïve patients had significantly longer PFS than lapatinib-treated patients (9.0 months vs. 5.4 months, p=0.001). ORR for lapatinib-treated patients was 23.2%. Thirty-one of 113 patients have brain metastasis. Median PFS was 6.7 months and intracranial ORR was 28%. For patients without concurrent radiotherapy and/or brain surgery, the ORR was very low (6.3%). But for patients receiving concurrent radiotherapy and/or brain surgery, the ORR was 66.7%, and three patients achieved complete response. Most common adverse event was diarrhea.
Conclusion
Pyrotinib-based therapy demonstrated promising effects in metastatic HER2-positive BC and showed activity in lapatinib-treated patients. For patients with brain metastasis, pyrotinib-based regimen without radiotherapy showed limited efficacy, but when combined with radiotherapy it showed promising intracranial control.
Citations
Citations to this article as recorded by
Neurotoxicity-sparing radiotherapy for brain metastases in breast cancer: a narrative review Dagmara Buczek, Renata Zaucha, Jacek Jassem Frontiers in Oncology.2024;[Epub] CrossRef
Comparison of the prognostic effect of pyrotinib plus trastuzumab and chemotherapy different lines therapy in HER2-positive advanced breast cancer Yangqingqing Zhou, Hui Wang, Jiao Yang, Fan Wang, Danfeng Dong, Xiaoai Zhao, Le Wang, Ruiyuan He, Zhiping Ruan, Jin Yang Journal of Chemotherapy.2024; : 1. CrossRef
HER2-positive metastatic breast cancer with brain metastases responds favorably to pyrotinib and trastuzumab-based treatment: A case report and literature review Min-long Chen, Wenjie Yu, Binbin Cui, Yijian Yu, Zhaosheng Ma Frontiers in Oncology.2023;[Epub] CrossRef
Efficacy and safety of inetetamab-containing regimens in patients with HER2-positive metastatic breast cancer: a real-world retrospective study in China Xiaoyu Liu, Peng Zhang, Chao Li, Xiang Song, Zhaoyun Liu, Wenna Shao, Sumei Li, Xinzhao Wang, Zhiyong Yu Frontiers in Oncology.2023;[Epub] CrossRef
Evolving management of HER2+ breast cancer brain metastases and leptomeningeal disease Matthew N. Mills, Whitney King, Aixa Soyano, Yolanda Pina, Brian J. Czerniecki, Peter A. Forsyth, Hatem Soliman, Hyo S. Han, Kamran A. Ahmed Journal of Neuro-Oncology.2022; 157(2): 249. CrossRef
Temporal Heterogeneity of HER2 Expression and Spatial Heterogeneity of 18F-FDG Uptake Predicts Treatment Outcome of Pyrotinib in Patients with HER2-Positive Metastatic Breast Cancer Chengcheng Gong, Cheng Liu, Zhonghua Tao, Jian Zhang, Leiping Wang, Jun Cao, Yannan Zhao, Yizhao Xie, Xichun Hu, Zhongyi Yang, Biyun Wang Cancers.2022; 14(16): 3973. CrossRef
Cost-Effectiveness of Pyrotinib Plus Capecitabine versus Lapatinib Plus Capecitabine for the Treatment of HER2-Positive Metastatic Breast Cancer in China: A Scenario Analysis of Health Insurance Coverage Yuwen Bao, Zhuolin Zhang, Xuan He, Lele Cai, Xiao Wang, Xin Li Current Oncology.2022; 29(9): 6053. CrossRef
An Insight into Molecular Targets of Breast Cancer Brain Metastasis Mohammed Kaleem, Mahmood Hassan Dalhat, Lubna Azmi, Turky Omar Asar, Wasim Ahmad, Maimonah Alghanmi, Amal Almostadi, Torki A. Zughaibi, Shams Tabrez International Journal of Molecular Sciences.2022; 23(19): 11687. CrossRef
Real-World Outcome and Prognostic Factors Among HER2-Positive Metastatic Breast Cancer Patients Receiving Pyrotinib-Based Therapy: A Multicenter Retrospective Analysis Jing Liu, Xianglu Sun, Qianyu Du, Jinghao Yao, Mengfen Dai, Qianqian Cheng, Han Xu, Yawei Li, Xiuli Liu, Mingliang Zhang, Yongchun Zhou, Yan Yang Breast Cancer: Targets and Therapy.2022; Volume 14: 491. CrossRef
Eribulin Efficacy on Brain Metastases in Heavily Pretreated Patients with Metastatic Breast Cancer Renaud Sabatier, Johan Martin, Cécile Vicier, Mathilde Guérin, Audrey Monneur, Magali Provansal, Louis Tassy, Carole Tarpin, Jean-Marc Extra, Frédéric Viret, Anthony Goncalves Journal of Clinical Medicine.2021; 10(6): 1272. CrossRef
Pyrotinib Combined With Vinorelbine in HER2-Positive Metastatic Breast Cancer: A Multicenter Retrospective Study Yi Li, Yixuan Qiu, Huihui Li, Ting Luo, Wei Li, Hong Wang, Bin Shao, Biyun Wang, Rui Ge Frontiers in Oncology.2021;[Epub] CrossRef
Multiple Administrations of Itraconazole Increase Plasma Exposure to Pyrotinib in Chinese Healthy Adults Yueyue Liu, Qian Zhang, Chao Lu, Wei Hu Drug Design, Development and Therapy.2021; Volume 15: 2485. CrossRef
Brain Metastases in HER2-Positive Breast Cancer: Current and Novel Treatment Strategies Alejandro Garcia-Alvarez, Andri Papakonstantinou, Mafalda Oliveira Cancers.2021; 13(12): 2927. CrossRef
Pyrotinib Plus Vinorelbine Versus Lapatinib Plus Capecitabine in Patients With Previously Treated HER2-Positive Metastatic Breast Cancer: A Multicenter, Retrospective Study Yizhao Xie, Yi Li, Luo Ting, Die Sang, Peng Yuan, Wei Li, Huihui Li, Rui Ge, Biyun Wang Frontiers in Oncology.2021;[Epub] CrossRef
The Efficacy of Pyrotinib as a Third- or Higher-Line Treatment in HER2-Positive Metastatic Breast Cancer Patients Exposed to Lapatinib Compared to Lapatinib-Naive Patients: A Real-World Study D. J Ouyang, Q. T Chen, M. Anwar, N. Xie, Q. C. Ouyang, P. Z. Fan, L. Y. Qian, G. N. Chen, E. X. Zhou, L. Guo, X. W. Gu, B. N. Ding, X. H. Yang, L. P. Liu, C. Deng, Z. Xiao, J. Li, Y. Q. Wang, S. Zeng, Shouman Wang, Wenjun Yi Frontiers in Pharmacology.2021;[Epub] CrossRef
Updates on Molecular Targeted Therapies for Intraparenchymal CNS Metastases Akanksha Sharma, Lauren Singer, Priya Kumthekar Cancers.2021; 14(1): 17. CrossRef
Purpose
Triple-negative breast cancer (TNBC) is highly malignant and has poor prognosis and a high mortality rate. The lack of effective therapy has spurred our investigation of new targets for treating this malignant cancer. Here, we identified RON (macrophage-stimulating 1 receptor) and MET (MET proto-oncogene, receptor tyrosine kinase) as a prognostic biomarker and therapeutic targets for potential TNBC treatment.
Materials and Methods
We analyzed RON and MET expression in 187 primary TNBC clinical samples with immunohistochemistry. We validated the targeted therapeutic effects of RON and MET in TNBC using three tyrosine kinase inhibitors (TKIs): BMS-777607, INCB28060, and tivantinib. The preclinical therapeutic efficacy of the TKIs was mainly estimated using a TNBC xenograft model.
Results
Patients with TNBC had widespread, abnormal expression of RON and MET. There was RON overexpression, MET overexpression, and RON and MET co-overexpression in 63 (33.7%), 63 (33.7%), and 43 cases (23.0%), respectively, which had poor prognosis and short survival. In vivo, the TKI targeting RON ant MET inhibited the activation of the downstream signaling molecules, inhibited TNBC cell migration and proliferation, and increased TNBC cell apoptosis; in the xenograft model, they significantly inhibited tumor growth and shrank tumor volumes. The TKI targeting RON and Met, such as BMS-777607 and tivantinib, yielded stronger anti-tumor effects than INCB28060.
Conclusion
RON and MET co-overexpression can be significant pathological characteristics in TNBC for poor prognosis. TKIs targeting RON and MET have stronger drug development potential for treating TNBC.
Citations
Citations to this article as recorded by
c-MET-positive circulating tumor cells and cell-free DNA as independent prognostic factors in hormone receptor-positive/HER2-negative metastatic breast cancer Jieun Park, Eun Sol Chang, Ji-Yeon Kim, Chaithanya Chelakkot, Minjung Sung, Ji-Young Song, Kyungsoo Jung, Ji Hye Lee, Jun Young Choi, Na Young Kim, Hyegyeong Lee, Mi-Ran Kang, Mi Jeong Kwon, Young Kee Shin, Yeon Hee Park, Yoon-La Choi Breast Cancer Research.2024;[Epub] CrossRef
MET alterations detection platforms and clinical implications in solid tumors: a comprehensive review of literature Pei Yuan, Xuemin Xue, Tian Qiu, Jianming Ying Therapeutic Advances in Medical Oncology.2024;[Epub] CrossRef
Targeting Receptor Tyrosine Kinases as a Novel Strategy for the Treatment of Triple-Negative Breast Cancer Sara K. Jaradat, Nehad M. Ayoub, Ahmed H. Al Sharie, Julia M. Aldaod Technology in Cancer Research & Treatment.2024;[Epub] CrossRef
Recent advancement in developing small molecular inhibitors targeting key kinase pathways against triple-negative breast cancer Rajibul Islam, Khor Poh Yen, Nur Najihah ’Izzati Mat Rani, Md. Selim Hossain Bioorganic & Medicinal Chemistry.2024; 112: 117877. CrossRef
TYRO3 and EPHA2 Expression Are Dysregulated in Breast Cancer Ananda Cristina Fernandes de Aguiar, Nancy Cristina Ferraz de Lucena Ferreira, Maria Amelia Carlos Souto Maior Borba, Darley de Lima Ferreira Filho, Glauber Moreira Leitão, Luiz Alberto Mattos, José Luiz de Lima Filho, Danyelly Bruneska Gondim Martins Cell Biochemistry and Function.2024;[Epub] CrossRef
Defining the Emergence of New Immunotherapy Approaches in Breast Cancer: Role of Myeloid-Derived Suppressor Cells María Luisa Sánchez-León, Carlos Jiménez-Cortegana, Silvia Silva Romeiro, Carmen Garnacho, Luis de la Cruz-Merino, Daniel J. García-Domínguez, Lourdes Hontecillas-Prieto, Víctor Sánchez-Margalet International Journal of Molecular Sciences.2023; 24(6): 5208. CrossRef
2D Nanosilicate for additive manufacturing: Rheological modifier, sacrificial ink and support bath Satyam Rajput, Kaivalya A. Deo, Tanmay Mathur, Giriraj Lokhande, Kanwar Abhay Singh, Yuxiang Sun, Daniel L. Alge, Abhishek Jain, Tapasree Roy Sarkar, Akhilesh K. Gaharwar Bioprinting.2022; 25: e00187. CrossRef
The MST1R/RON Tyrosine Kinase in Cancer: Oncogenic Functions and Therapeutic Strategies Alex Cazes, Betzaira G. Childers, Edgar Esparza, Andrew M. Lowy Cancers.2022; 14(8): 2037. CrossRef
Antibody-drug Conjugate PCMC1D3-Duocarmycin SA as a Novel Therapeutic
Entity for Targeted Treatment of Cancers Aberrantly Expressing
MET Receptor Tyrosine Kinase Rachel Hudson, Hang-Ping Yao, Sreedhar Reddy Suthe, Dhavalkumar Patel, Ming-Hai Wang Current Cancer Drug Targets.2022; 22(4): 312. CrossRef
Pharmaceutical strategies in the emerging era of antibody-based biotherapeutics for the treatment of cancers overexpressing MET receptor tyrosine kinase Hang-Ping Yao, Xiang-Min Tong, Ming-Hai Wang Drug Discovery Today.2021; 26(1): 106. CrossRef
Small-Molecule Drug Discovery in Triple Negative Breast Cancer: Current Situation and Future Directions Minru Liao, Jin Zhang, Guan Wang, Leiming Wang, Jie Liu, Liang Ouyang, Bo Liu Journal of Medicinal Chemistry.2021; 64(5): 2382. CrossRef
The MSP‐RON pathway regulates liver fibrosis through transforming growth factor beta‐dependent epithelial–mesenchymal transition Tianhao Weng, Dong Yan, Danrong Shi, Miaojin Zhu, Yizhi Liu, Zhigang Wu, Taoming Tang, Linwei Zhu, Hong Zhang, Hangping Yao, Lanjuan Li Liver International.2021; 41(8): 1956. CrossRef
MicroRNA Expression Profiling of Lung Cancer with Differential Expression of the RON Receptor Tyrosine Kinase Huilin Ou, Keda Chen, Hongcheng Wu, Yuan Seng Wu Journal of Oncology.2021; 2021: 1. CrossRef
RON Mediates Tumor-Promoting Effects in Endometrial Adenocarcinoma Qin Yu, Jianzhang Wang, Tiantian Li, Xinxin Xu, Xinyue Guo, Shaojie Ding, Libo Zhu, Gen Zou, Yichen Chen, Xinmei Zhang, Bing Wang BioMed Research International.2021; 2021: 1. CrossRef
Drug Repositioning and Subgroup Discovery for Precision Medicine Implementation in Triple Negative Breast Cancer Zainab Al-Taie, Mark Hannink, Jonathan Mitchem, Christos Papageorgiou, Chi-Ren Shyu Cancers.2021; 13(24): 6278. CrossRef
Clinical value and potential mechanisms of COL8A1 upregulation in breast cancer: a comprehensive analysis Wei Peng, Jian-Di Li, Jing-Jing Zeng, Xiao-Ping Zou, Deng Tang, Wei Tang, Min-Hua Rong, Ying Li, Wen-Bin Dai, Zhong-Qing Tang, Zhen-Bo Feng, Gang Chen Cancer Cell International.2020;[Epub] CrossRef
Purpose
Osimertinib is a third-generation, irreversible, oral epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) that potently and selectively inhibits both EGFR sensitizing mutation and EGFR T790M and has demonstrated efficacy in non-small cell lung cancer (NSCLC) central nervous system (CNS) metastases. We present results of a subgroup analysis of Korean patients from the pooled data of two global phase II trials: AURA extension (NCT01802632) and AURA2 (NCT02094261).
Materials and Methods
Enrolled patients had EGFR T790M-positive NSCLC and disease progression during or after EGFR-TKI therapy. Patients received osimertinib 80 mg orally once daily until disease progression. The primary endpoint was objective response rate (ORR).
Results
In total, 66 Korean patients received osimertinib treatment with a median treatment duration of 19 months. In the evaluable-for-response population (n=62), ORR was 74% (95% confidence interval [CI], 61.5 to 84.5) and median duration of response was 9.8 months (95% CI, 7.1 to 16.8). In the full analysis set (n=66), median progression-free survival was 10.9 months (95% CI, 8.3 to 15.0; data cutoff November 1, 2016), and median overall survival was 29.2 months (95% CI, 24.8 to 35.7; data cutoff May 1, 2018). Eight patients with CNS metastases were evaluable for response, none of whom showed CNS progression. The most common adverse events were rash (53%), cough (33%), paronychia, diarrhea, and decreased appetite (each 32%).
Conclusion
Efficacy and safety profiles of osimertinib in this subgroup are consistent with the global phase II pooled population, which supports osimertinib as a recommended treatment for Korean patients with T790M positive NSCLC.
Citations
Citations to this article as recorded by
Pan-Asian adapted ESMO Clinical Practice Guidelines for the diagnosis, treatment and follow-up of patients with oncogene-addicted metastatic non-small-cell lung cancer S.-H. Lee, J. Menis, T.M. Kim, H.R. Kim, C. Zhou, S.A. Kurniawati, K. Prabhash, H. Hayashi, D.D.-W. Lee, M.S. Imasa, Y.L. Teh, J.C.-H. Yang, T. Reungwetwattana, V. Sriuranpong, C.-E. Wu, Y. Ang, M. Sabando, M. Thiagarajan, H. Mizugaki, V. Noronha, M. Yuli ESMO Open.2024; 9(12): 103996. CrossRef
The role of brain radiotherapy for EGFR- and ALK-positive non-small-cell lung cancer with brain metastases: a review Valerio Nardone, Caterina Romeo, Emma D’Ippolito, Pierpaolo Pastina, Maria D’Apolito, Luigi Pirtoli, Michele Caraglia, Luciano Mutti, Giovanna Bianco, Antonella Consuelo Falzea, Rocco Giannicola, Antonio Giordano, Pierosandro Tagliaferri, Claudia Vincigue La radiologia medica.2023; 128(3): 316. CrossRef
The Relationship Between Short-Term Surrogate Endpoint Indicators and mPFS and mOS in Clinical Trials of Malignant Tumors: A Case Study of Approved Molecular Targeted Drugs for Non-Small-Cell Lung Cancer in China Mingjun Rui, Zijing Wang, Zhengyang Fei, Yao Wu, Yingcheng Wang, Lei Sun, Ye Shang, Hongchao Li Frontiers in Pharmacology.2022;[Epub] CrossRef
Efficacy and Safety of SH-1028 in Patients With EGFR T790M-Positive NSCLC: A Multicenter, Single-Arm, Open-Label, Phase 2 Trial Anwen Xiong, Shengxiang Ren, Huaimin Liu, Liyun Miao, Lei Wang, Jianhua Chen, Wei Li, Runpu Li, Xiang Wang, Zhiwei Lu, Donglin Wang, Xiaohong Wu, Zhihua Liu, Ligang Xing, Yimin Mao, Chunling Liu, Aiping Zeng, Hongrui Niu, Yingying Du, Yuping Sun, Yueyin P Journal of Thoracic Oncology.2022; 17(10): 1216. CrossRef
Treatment of Brain Metastases of Non-Small Cell Lung Carcinoma Agnieszka Rybarczyk-Kasiuchnicz, Rodryg Ramlau, Katarzyna Stencel International Journal of Molecular Sciences.2021; 22(2): 593. CrossRef
Purpose
Amplified mesenchymal-epithelial transition factor, MET, is a receptor tyrosine kinase (RTK) that has been considered a druggable target in non-small cell lung cancer (NSCLC). Although multiple MET tyrosine kinase inhibitors (TKIs) are being actively developed for MET-driven NSCLC, the mechanisms of acquired resistance to MET-TKIs have not been well elucidated. To understand the mechanisms of resistance and establish therapeutic strategies, we developed an in vitro model using the MET-amplified NSCLC cell line EBC-1.
Materials and Methods
We established capmatinib-resistant NSCLC cell lines and identified alternative signaling pathways using 3′ mRNA sequencing and human phospho-RTK arrays. Copy number alterations were evaluated by quantitative polymerase chain reaction and cell proliferation assay; activation of RTKs and downstream effectors were compared between the parental cell line EBC-1 and the resistant cell lines.
Results
We found that EBC-CR1 showed an epidermal growth factor receptor (EGFR)‒dependent growth and sensitivity to afatinib, an irreversible EGFR TKI. EBC-CR2 cells that had overexpression of EGFR-MET heterodimer dramatically responded to combined capmatinib with afatinib. In addition, EBC-CR3 cells derived from EBC-CR1 cells that activated EGFR with amplified phosphoinositide-3 kinase catalytic subunit α (PIK3CA) were sensitive to combined afatinib with BYL719, a phosphoinositide 3-kinase α (PI3Kα) inhibitor.
Conclusion
Our in vitro studies suggested that activation of EGFR signaling and/or genetic alteration of downstream effectors like PIK3CA were alternative resistance mechanisms used by capmatinib-resistant NSCLC cell lines. In addition, combined treatments with MET, EGFR, and PI3Kα inhibitors may be effective therapeutic strategies in capmatinib-resistant NSCLC patients.
Citations
Citations to this article as recorded by
Immunohistochemical characteristics and potential therapeutic regimens of hepatoid adenocarcinoma of the stomach: a study of 139 cases Xuesong Yang, Yan Wu, Anqiang Wang, Xiuli Ma, Kai Zhou, Ke Ji, Xin Ji, Ji Zhang, Xiaojiang Wu, ZhongWu Li, Zhaode Bu The Journal of Pathology: Clinical Research.2024;[Epub] CrossRef
My battle with cancer. Part 1 Mikhail V. Blagosklonny Oncoscience.2024; 11: 1. CrossRef
SOS2 modulates the threshold of EGFR signaling to regulate osimertinib efficacy and resistance in lung adenocarcinoma Patricia L. Theard, Amanda J. Linke, Nancy E. Sealover, Brianna R. Daley, Johnny Yang, Katherine Cox, Robert L. Kortum Molecular Oncology.2024; 18(3): 641. CrossRef
Synthetic approaches and application of representative clinically approved fluorine-enriched anti-cancer medications He-Nan Liu, Ying Zhu, Yuan Chi, Fei-Fei Sun, Li-Shen Shan, Ya-Tao Wang, Bing Dai European Journal of Medicinal Chemistry.2024; 276: 116722. CrossRef
Multifunctional dendrimer-peptide conjugates for MET receptor-specific imaging of cancer cells Jin Woong Lee, Kwangok P. Nickel, Rachel L. Minne, Justin J. Jeffery, Eduardo Aluicio-Sarduy, Carter Kim, DaWon Kim, Piper A. Rawding, Michael J. Poellmann, Narsimha Mamidi, Jonathan W. Engle, Jung Heon Lee, Hansoo Park, Reinier Hernandez, Randall J. Kimp Nano Today.2024; 59: 102509. CrossRef
Non-small cell lung carcinoma (NSCLC): Implications on molecular pathology and advances in early diagnostics and therapeutics Hafiza Padinharayil, Jinsu Varghese, Mithun Chacko John, Golgodu Krishnamurthy Rajanikant, Cornelia M. Wilson, Minnatallah Al-Yozbaki, Kaviyarasi Renu, Saikat Dewanjee, Rupa Sanyal, Abhijit Dey, Anirban Goutam Mukherjee, Uddesh Ramesh Wanjari, Abilash Val Genes & Diseases.2023; 10(3): 960. CrossRef
Synergistic therapeutic potential of alpelisib in cancers (excluding breast cancer): Preclinical and clinical evidences Yuhao Ye, Zhiyu Huang, Maoqing Zhang, Jiayue Li, Yiqiong Zhang, Chenghua Lou Biomedicine & Pharmacotherapy.2023; 159: 114183. CrossRef
Quinolines: Privileged Scaffolds for Developing New Anti‐neurodegenerative Agents M.Sc.Shivani Chauhan, Tarana Umar, Manpreet K. Aulakh ChemistrySelect.2023;[Epub] CrossRef
A multiparametric fluorescent visualization approach for detecting drug resistance in living cancer cells Zhilan Zhou, Ya Wang, Zhengtao Shao, Guixi Zhang, Hang Jiang, Yiyuan Tang, Zening Huang, Yingdi Zhu, Juan Li Talanta.2023; 259: 124564. CrossRef
Targeting MET: Discovery of Small Molecule Inhibitors as Non-Small Cell Lung Cancer Therapy Chaofan Wang, Xiaoyun Lu Journal of Medicinal Chemistry.2023; 66(12): 7670. CrossRef
Current Indications and Future Landscape of Bispecific Antibodies for the Treatment of Lung Cancer Hugo Arasanz, Luisa Chocarro, Leticia Fernández-Rubio, Ester Blanco, Ana Bocanegra, Miriam Echaide, Ibone Labiano, Ana Elsa Huerta, Maria Alsina, Ruth Vera, David Escors, Grazyna Kochan International Journal of Molecular Sciences.2023; 24(12): 9855. CrossRef
An Observatory for the MET Oncogene: A Guide for Targeted Therapies Dogus M. Altintas, Paolo M. Comoglio Cancers.2023; 15(18): 4672. CrossRef
Advances of clinically approved small-molecule drugs for the treatment of non-small cell lung cancer Zhen-Xi Niu, Ya-Tao Wang, Nan Lu, Jin-Feng Sun, Peng Nie, Piet Herdewijn European Journal of Medicinal Chemistry.2023; 261: 115868. CrossRef
Epigenetic regulation in lung cancer Shahin Ramazi, Maedeh Dadzadi, Zahra Sahafnejad, Abdollah Allahverdi MedComm.2023;[Epub] CrossRef
SOS1 and KSR1 modulate MEK inhibitor responsiveness to target resistant cell populations based on PI3K and KRAS mutation status Brianna R. Daley, Heidi M. Vieira, Chaitra Rao, Jacob M. Hughes, Zaria M. Beckley, Dianna H. Huisman, Deepan Chatterjee, Nancy E. Sealover, Katherine Cox, James W. Askew, Robert A. Svoboda, Kurt W. Fisher, Robert E. Lewis, Robert L. Kortum Proceedings of the National Academy of Sciences.2023;[Epub] CrossRef
KRAS and MET in non-small-cell lung cancer: two of the new kids on the ‘drivers’ block Juan Esteban Garcia-Robledo, Rafael Rosell, Alejandro Ruíz-Patiño, Carolina Sotelo, Oscar Arrieta, Lucia Zatarain-Barrón, Camila Ordoñez, Elvira Jaller, Leonardo Rojas, Alessandro Russo, Diego de Miguel-Pérez, Christian Rolfo, Andrés F. Cardona Therapeutic Advances in Respiratory Disease.2022;[Epub] CrossRef
MET Exon 14 Splice-Site Mutations Preferentially Activate KRAS Signaling to Drive Tumourigenesis Daniel Lu, Amy Nagelberg, Justine LM Chow, Yankuan T Chen, Quentin Michalchuk, Romel Somwar, William W. Lockwood Cancers.2022; 14(6): 1378. CrossRef
hOA-DN30: a highly effective humanized single-arm MET antibody inducing remission of ‘MET-addicted’ cancers Ilaria Martinelli, Chiara Modica, Cristina Chiriaco, Cristina Basilico, James M. Hughes, Simona Corso, Silvia Giordano, Paolo M. Comoglio, Elisa Vigna Journal of Experimental & Clinical Cancer Research.2022;[Epub] CrossRef
PIK3CAMutations Drive Therapeutic Resistance in Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer Aryana R. Rasti, Amy Guimaraes-Young, Farrah Datko, Virginia F. Borges, Dara L. Aisner, Elena Shagisultanova JCO Precision Oncology.2022;[Epub] CrossRef
Protein tyrosine kinase inhibitor resistance in malignant tumors: molecular mechanisms and future perspective Yang Yang, Shuo Li, Yujiao Wang, Yi Zhao, Qiu Li Signal Transduction and Targeted Therapy.2022;[Epub] CrossRef
MET Signaling Pathways, Resistance Mechanisms, and Opportunities for Target Therapies Solange Rivas, Arnaldo Marín, Suraj Samtani, Evelin González-Feliú, Ricardo Armisén International Journal of Molecular Sciences.2022; 23(22): 13898. CrossRef
Advances in the Lung Cancer Immunotherapy Approaches Hafiza Padinharayil, Reema Rose Alappat, Liji Maria Joy, Kavya V. Anilkumar, Cornelia M. Wilson, Alex George, Abilash Valsala Gopalakrishnan, Harishkumar Madhyastha, Thiyagarajan Ramesh, Ezhaveni Sathiyamoorthi, Jintae Lee, Raja Ganesan Vaccines.2022; 10(11): 1963. CrossRef
A comprehensive review on the biological interest of quinoline and its derivatives Basavarajaiah Suliphuldevara Matada, Raviraj Pattanashettar, Nagesh Gunavanthrao Yernale Bioorganic & Medicinal Chemistry.2021; 32: 115973. CrossRef
Combination of HGF/MET-targeting agents and other therapeutic strategies in cancer Fatemeh Moosavi, Elisa Giovannetti, Godefridus J. Peters, Omidreza Firuzi Critical Reviews in Oncology/Hematology.2021; 160: 103234. CrossRef
Novel Therapies for Metastatic Non-Small Cell Lung Cancer with MET Exon 14 Alterations: A Spotlight on Capmatinib Aaron Tan, Tracy J Loh, Xue Lin Kwang, Gek San Tan, Kiat Hon Lim, Daniel SW Tan Lung Cancer: Targets and Therapy.2021; Volume 12: 11. CrossRef
Discovery of Potent, Selective Triazolothiadiazole-Containing c-Met Inhibitors Qing Tang, Alex M. Aronov, David D. Deininger, Simon Giroux, David J. Lauffer, Pan Li, Jianglin Liang, Kira McGinty, Steven Ronkin, Rebecca Swett, Nathan Waal, Diane Boucher, Pamella J. Ford, Cameron S. Moody ACS Medicinal Chemistry Letters.2021; 12(6): 955. CrossRef
Tyrosine Kinase Inhibitors, Antibody-Drug Conjugates, and Proteolysis-Targeting Chimeras: The Pharmacology of Cutting-Edge Lung Cancer Therapies Jennifer W. Carlisle, R. Donald Harvey American Society of Clinical Oncology Educational Book.2021; (41): e286. CrossRef
Response to crizotinib in a patient with MET‐amplified hepatocellular carcinoma Qinglian Chen, Chunfeng Xie, Kunliang Feng, Haijun Huang, Chengming Xiong, Tengjiao Lin, Wenjing Wang, Mian Xu, Xianwei Yang, Chong Zhong Hepatology Research.2021; 51(11): 1164. CrossRef
New FDA oncology small molecule drugs approvals in 2020: Mechanism of action and clinical applications Thais Cristina Mendonça Nogueira, Marcus Vinicius Nora de Souza Bioorganic & Medicinal Chemistry.2021; 46: 116340. CrossRef
Genetic evolution to tyrosine kinase inhibitory therapy in patients with EGFR-mutated non-small-cell lung cancer Alex Martinez-Marti, Enriqueta Felip, Francesco Mattia Mancuso, Ginevra Caratú, Judit Matito, Paolo Nuciforo, Irene Sansano, Nely Diaz-Mejia, Susana Cedrés, Ana Callejo, Patricia Iranzo, Nuria Pardo, Josep Maria Miquel, Alejandro Navarro, Ana Vivancos, Mi British Journal of Cancer.2021; 125(11): 1561. CrossRef
A Biparatopic Antibody–Drug Conjugate to Treat MET-Expressing Cancers, Including Those that Are Unresponsive to MET Pathway Blockade John O. DaSilva, Katie Yang, Oliver Surriga, Thomas Nittoli, Arthur Kunz, Matthew C. Franklin, Frank J. Delfino, Shu Mao, Feng Zhao, Jason T. Giurleo, Marcus P. Kelly, Sosina Makonnen, Carlos Hickey, Pamela Krueger, Randi Foster, Zhaoyuan Chen, Marc W. Re Molecular Cancer Therapeutics.2021; 20(10): 1966. CrossRef
Development and full validation of an LC–MS/MS methodology to quantify capmatinib (INC280) following intragastric administration to rats Xiaoguang Fan, Guanghu Yang, Wenjuan Cui, Qin Liu, Zhaolong Zhang, Zhikun Zhang Biomedical Chromatography.2020;[Epub] CrossRef
A Randomized-Controlled Phase 2 Study of the MET Antibody Emibetuzumab in Combination with Erlotinib as First-Line Treatment for EGFR Mutation–Positive NSCLC Patients Giorgio Scagliotti, Denis Moro-Sibilot, Jens Kollmeier, Adolfo Favaretto, Eun Kyung Cho, Heidrun Grosch, Martin Kimmich, Nicolas Girard, Chun-Ming Tsai, Te-Chun Hsia, Matteo Brighenti, Christian Schumann, Xuejing Aimee Wang, Sameera R. Wijayawardana, Aaro Journal of Thoracic Oncology.2020; 15(1): 80. CrossRef
Targeted Therapy and Checkpoint Immunotherapy in Lung Cancer Roberto Ruiz-Cordero, Walter Patrick Devine Surgical Pathology Clinics.2020; 13(1): 17. CrossRef
Meta-analysis of functional expression and mutational analysis of c-Met in various cancers Murugesan Sivakumar, Murugesan Jayakumar, Palaniappan Seedevi, Palaniappan Sivasankar, Muthu Ravikumar, Sundharaiyya Surendar, Tamilselvi Murugan, Shahid S. Siddiqui, Sivakumar Loganathan Current Problems in Cancer.2020; 44(4): 100515. CrossRef
Targeting the HGF/MET Axis in Cancer Therapy: Challenges in Resistance and Opportunities for Improvement Xing Huang, Enliang Li, Hang Shen, Xun Wang, Tianyu Tang, Xiaozhen Zhang, Jian Xu, Zengwei Tang, Chengxiang Guo, Xueli Bai, Tingbo Liang Frontiers in Cell and Developmental Biology.2020;[Epub] CrossRef
Statins use and its impact in EGFR‐TKIs resistance to prolong the survival of lung cancer patients: A Cancer registry cohort study in Taiwan Phung‐Anh Nguyen, Chih‐Cheng Chang, Cooper J. Galvin, Yao‐Chin Wang, Soo Yeon An, Chih‐Wei Huang, Yu‐Hsiang Wang, Min‐Huei Hsu, Yu‐Chuan (Jack) Li, Hsuan‐Chia Yang Cancer Science.2020; 111(8): 2965. CrossRef
A Single-Step, High-Dose Selection Scheme Reveals Distinct Mechanisms of Acquired Resistance to Oncogenic Kinase Inhibition in Cancer Cells Kenneth J. Finn, Scott E. Martin, Jeff Settleman Cancer Research.2020; 80(1): 79. CrossRef
Emerging therapies for non-small cell lung cancer Chao Zhang, Natasha B. Leighl, Yi-Long Wu, Wen-Zhao Zhong Journal of Hematology & Oncology.2019;[Epub] CrossRef
Capmatinib for the treatment of non-small cell lung cancer Johan Filip Vansteenkiste, Charlotte Van De Kerkhove, Els Wauters, Pierre Van Mol Expert Review of Anticancer Therapy.2019; 19(8): 659. CrossRef
Afatinib Overcomes Pemetrexed-Acquired Resistance in Non-Small Cell Lung Cancer Cells Harboring an EML4-ALK Rearrangement Ji-Hyun Kwon, Kui-Jin Kim, Ji Hea Sung, Koung Jin Suh, Ji Yun Lee, Ji-Won Kim, Se Hyun Kim, Jeong-Ok Lee, Jin Won Kim, Yu Jung Kim, Keun-Wook Lee, Jee Hyun Kim, Soo-Mee Bang, Soyeon Kim, Sung-Soo Yoon, Jong Seok Lee Cells.2019; 8(12): 1538. CrossRef
DYRK1A inhibition suppresses STAT3/EGFR/Met signalling and sensitizes EGFR wild‐type NSCLC cells to AZD9291 Yang‐ling Li, Ke Ding, Xiu Hu, Lin‐wen Wu, Dong‐mei Zhou, Ming‐jun Rao, Neng‐ming Lin, Chong Zhang Journal of Cellular and Molecular Medicine.2019; 23(11): 7427. CrossRef
MiR-1246 Promotes Metastasis and Invasion of A549 cells by Targeting GSK-3β‒Mediated Wnt/β-Catenin Pathway Fan Yang, Hairong Xiong, Li Duan, Qian Li, Xin Li, Yongqin Zhou Cancer Research and Treatment.2019; 51(4): 1420. CrossRef
Seonggyu Byeon, Youjin Kim, Sung Won Lim, Jang Ho Cho, Sehoon Park, Jiyun Lee, Jong-Mu Sun, Yoon-La Choi, Se-Hoon Lee, Jin Seok Ahn, Keunchil Park, Myung-Ju Ahn
Cancer Res Treat. 2019;51(2):623-631. Published online July 23, 2018
Purpose
Epidermal growth factor receptor (EGFR) exon 20 insertion mutations account for approximately 4% of all EGFR mutations. Given the rarity of this mutation, its clinical outcomes are not fully established.
Materials and Methods
Between 2009 and 2017, non-small cell lung cancer (NSCLC) patients who showed an exon 20 insertion were retrospectively reviewed for clinical characteristics and outcomes, including responses to chemotherapy (CTx) or targeted therapy.
Results
Of 3,539 NSCLC patients who harbored an activating EGFR mutation, 56 (1.6%) had an exon 20 insertion. Of the advanced NSCLC patients, 27 of 1,479 (1.8%) had an exon 20 insertion. The median overall survival was 29.4 months (95% confidence interval 9.3 to 49.6) for 27 advancedNSCLC patients. The 22 patientswho received systemic CTx achieved a 50.0% response rate and a 77.2% disease control rate, with 4.2 months of progressionfree survival. Six patients received EGFR tyrosine kinase inhibitors (TKIs). Three of the four patients that had only an exon 20 insertion showed progressive disease, while one showed stable disease. The othertwo patients had an exon 20 insertion and another EGFR mutation and achieved a partial response.
Conclusion
The incidence of an exon 20 insertion mutation is rare in Korea and occasionally accompanied by other common EGFR mutations. Although the response to systemic CTx. in these patients is comparable to that of patients with other mutations, the response rate to firstor second-generation EGFR TKIs is quite low. Therefore, the development of a more efficient agent is urgently needed.
Citations
Citations to this article as recorded by
First-Line Mobocertinib Versus Platinum-Based Chemotherapy in Patients With
EGFR
Exon 20 Insertion–Positive Metastatic Non–Small Cell Lung Cancer in the Phase III EXCLAIM-2 Trial
Pasi A. Jänne, Bin-Chao Wang, Byoung Chul Cho, Jun Zhao, Juan Li, Maximilian Hochmair, Solange Peters, Benjamin Besse, Nick Pavlakis, Joel W. Neal, Terufumi Kato, Yi-Long Wu, Danny Nguyen, Junjing Lin, Jianchang Lin, Florin Vranceanu, Annette Szumski, Hua Journal of Clinical Oncology.2025;[Epub] CrossRef
Advances in the Diagnosis and Treatment of Advanced Non–Small-Cell Lung Cancer With EGFR Exon 20 Insertion Mutation Jingwen Liu, Yan Xiang, Tingwen Fang, Lulin Zeng, Ao Sun, Yixiang Lin, Kaihua Lu Clinical Lung Cancer.2024; 25(2): 100. CrossRef
Unmet needs in EGFR exon 20 insertion mutations in Central and Eastern Europe: reimbursement, diagnostic procedures, and treatment availability Maximilian J. Hochmair, Mojca Unk, Jelena Spasic, Timur Cerić, Assia Konsoulova, Mircea Dediu, Krisztina Bogos, Alinta Hegmane, Kersti Oselin, Marko Stojiljkovic, Tina Roblek, Marko Jakopovic BMC Proceedings.2024;[Epub] CrossRef
Clinical outcomes in patients with non-small cell lung cancer harboring EGFR Exon20 in-frame insertions in the near-loop and far-loop: Results from LC-SCRUM-Asia Masanobu Okahisa, Hibiki Udagawa, Shingo Matsumoto, Terufumi Kato, Hiroshi Yokouchi, Naoki Furuya, Ryota Kanemaru, Ryo Toyozawa, Akihiro Nishiyama, Kadoaki Ohashi, Shingo Miyamoto, Kazumi Nishino, Atsushi Nakamura, Eiji Iwama, Seiji Niho, Hajime Oi, Tetsu Lung Cancer.2024; 191: 107798. CrossRef
The current landscape, advancements, and prospects in the treatment of patients with EGFR exon 20 insertion mutations warrant scientific elucidation Xiuyue Man, Xueru Sun, Chen Chen, Yan Xiang, Jing Zhang, Lei Yang Frontiers in Oncology.2024;[Epub] CrossRef
Real-life comparison of afatinib and erlotinib in non-small cell lung cancer with rare EGFR exon 18 and exon 20 mutations: a Turkish Oncology Group (TOG) study Pınar Gursoy, Ali Murat Tatli, Dilek Erdem, Erdem Goker, Emir Celik, Nebi Serkan Demirci, Abdullah Sakin, Muhammed Mustafa Atci, Ertuğrul Bayram, Tuğba Akın Telli, Burak Bilgin, Ahmet Bilici, Baran Akangunduz, Sevinç Balli, Ahmet Demirkazik, Fatih Selçukb Journal of Cancer Research and Clinical Oncology.2023; 149(2): 865. CrossRef
Comparative effectiveness of mobocertinib and standard of care in patients with NSCLC with EGFR exon 20 insertion mutations: An indirect comparison Sai-Hong I. Ou, Huamao M. Lin, Jin-Liern Hong, Yu Yin, Shu Jin, Jianchang Lin, Minal Mehta, Pingkuan Zhang, Danny Nguyen, Joel W. Neal Lung Cancer.2023; 179: 107186. CrossRef
EGFR and ERBB2 exon 20 insertion/duplication in advanced non–small cell lung cancer: genomic profiling and clinicopathologic features Ramakrishna R. Sompallae, Bilge Dundar, Natalya V. Guseva, Aaron D. Bossler, Deqin Ma Frontiers in Oncology.2023;[Epub] CrossRef
Characteristics, treatment patterns, and clinical outcomes in patients with advanced non-small cell lung cancer harboring EGFR exon 20 insertions Ying-Ting Liao, Lei-Chi Wang, Ruei-Lin Sun, Yi-Chen Yeh, Hsu-Ching Huang, Chia-I Shen, Yen-Han Tseng, Tsu-Hui Hsiao, Heng-Sheng Chao, Yung-Hung Luo, Yuh-Min Chen, Chi-Lu Chiang Journal of Cancer Research and Clinical Oncology.2023; 149(12): 10365. CrossRef
EGFR exon20 insertion mutations in non-small cell lung cancer: Clinical implications and recent advances in targeted therapies Qianming Bai, Jialei Wang, Xiaoyan Zhou Cancer Treatment Reviews.2023; 120: 102605. CrossRef
A comprehensive overview of the heterogeneity of EGFR exon 20 variants in NSCLC and (pre)clinical activity to currently available treatments Fenneke Zwierenga, Bianca A.M.H. van Veggel, Anke van den Berg, Harry J.M. Groen, Lili Zhang, Matthew R. Groves, K. Kok, E.F. Smit, T. Jeroen N. Hiltermann, Adrianus J. de Langen, Anthonie J. van der Wekken Cancer Treatment Reviews.2023; 120: 102628. CrossRef
Epidemiological characteristics and therapeutic advances of EGFR exon 20 insertion mutations in non‐small cell lung cancer Binyang Pan, Jiaqi Liang, Haochun Shi, Kungeng Rao, Weigang Guo, Cheng Zhan Thoracic Cancer.2023; 14(33): 3247. CrossRef
Aumolertinib-based comprehensive treatment for an uncommon site of EGFR exon 20 insertion mutations with multiple metastases non-small cell lung cancer: a case report Youjun Deng, Chenglin Yang, Wenyi Liu, Songhua Cai, Xiaotong Guo Anti-Cancer Drugs.2022; 33(4): 406. CrossRef
Population pharmacokinetics of mobocertinib in healthy volunteers and patients with non–small cell lung cancer Neeraj Gupta, Philippe B. Pierrillas, Michael J. Hanley, Steven Zhang, Paul M. Diderichsen CPT: Pharmacometrics & Systems Pharmacology.2022; 11(6): 731. CrossRef
Amivantamab and Mobocertinib in Exon 20 insertions EGFR Mutant Lung Cancer, Challenge To The Current Guidelines Timothée Olivier, Vinay Prasad Translational Oncology.2022; 23: 101475. CrossRef
Poziotinib for EGFR exon 20-mutant NSCLC: Clinical efficacy, resistance mechanisms, and impact of insertion location on drug sensitivity Yasir Y. Elamin, Jacqulyne P. Robichaux, Brett W. Carter, Mehmet Altan, Hai Tran, Don L. Gibbons, Simon Heeke, Frank V. Fossella, Vincent K. Lam, Xiuning Le, Marcelo V. Negrao, Monique B. Nilsson, Anisha Patel, R.S.K. Vijayan, Jason B. Cross, Jianjun Zhan Cancer Cell.2022; 40(7): 754. CrossRef
EGFR exon 20 insertion variants A763_Y764insFQEA and D770delinsGY confer favorable sensitivity to currently approved EGFR-specific tyrosine kinase inhibitors Guangjian Yang, Yaning Yang, Jiaqi Hu, Haiyan Xu, Shuyang Zhang, Yan Wang Frontiers in Pharmacology.2022;[Epub] CrossRef
The mechanism of action of different generations of EGFR-inhibitors in malignant lung tumors. Literature review and data synthesis Ainur F. Nasretdinov, Konstantin V. Menshikov, Alexander V. Sultanbaev, Shamil I. Musin, Nadezda I. Sultanbaeva, Irina A. Men'shikova Journal of Modern Oncology.2022; 24(3): 340. CrossRef
Mobocertinib (TAK-788) in EGFR Exon 20 Insertion+ Metastatic NSCLC: Patient-Reported Outcomes from EXCLAIM Extension Cohort Maria Garcia Campelo, Caicun Zhou, Suresh Ramalingam, Huamao Lin, Tae Kim, Gregory Riely, Tarek Mekhail, Danny Nguyen, Erin Goodman, Minal Mehta, Sanjay Popat, Pasi Jänne Journal of Clinical Medicine.2022; 12(1): 112. CrossRef
Osimertinib for Chinese advanced non-small cell lung cancer patients harboring diverse EGFR exon 20 insertion mutations Guang-Jian Yang, Jun Li, Hai-Yan Xu, Yang Sun, Liu Liu, Hong-Shuai Li, Lu Yang, Yuan Zhang, Guo-Hui Li, Yan Wang Lung Cancer.2021; 152: 39. CrossRef
Epidemiological and clinical burden of EGFR Exon 20 insertion in advanced non-small cell lung cancer: A systematic literature review Heather Burnett, Helena Emich, Chris Carroll, Naomi Stapleton, Parthiv Mahadevia, Tracy Li, Rama Krishna Kancha PLOS ONE.2021; 16(3): e0247620. CrossRef
Response to Standard Therapies and Comprehensive Genomic Analysis for Patients with Lung Adenocarcinoma with EGFR Exon 20 Insertions Noura J. Choudhury, Adam J. Schoenfeld, Jessica Flynn, Christina J. Falcon, Hira Rizvi, Charles M. Rudin, Mark G. Kris, Maria E. Arcila, Glenn Heller, Helena A. Yu, Marc Ladanyi, Gregory J. Riely Clinical Cancer Research.2021; 27(10): 2920. CrossRef
EGFR Exon 20 Insertion Mutations: Clinicopathological Characteristics and Treatment Outcomes in Advanced Non–Small Cell Lung Cancer Jose Luis Leal, Marliese Alexander, Malinda Itchins, Gavin M. Wright, Steven Kao, Brett G.M. Hughes, Nick Pavlakis, Stephen Clarke, Anthony J Gill, Hannah Ainsworth, Benjamin Solomon, Thomas John Clinical Lung Cancer.2021; 22(6): e859. CrossRef
Activity and Safety of Mobocertinib (TAK-788) in Previously Treated Non–Small Cell Lung Cancer with EGFR Exon 20 Insertion Mutations from a Phase I/II Trial Gregory J. Riely, Joel W. Neal, D. Ross Camidge, Alexander I. Spira, Zofia Piotrowska, Daniel B. Costa, Anne S. Tsao, Jyoti D. Patel, Shirish M. Gadgeel, Lyudmila Bazhenova, Viola W. Zhu, Howard L. West, Tarek Mekhail, Ryan D. Gentzler, Danny Nguyen, Sylv Cancer Discovery.2021; 11(7): 1688. CrossRef
EGFR Exon 20 Insertion in Metastatic Non-Small-Cell Lung Cancer: Survival and Clinical Efficacy of EGFR Tyrosine-Kinase Inhibitor and Chemotherapy Samy Chelabi, Xavier Mignard, Karen Leroy, Isabelle Monnet, Solenn Brosseau, Nathalie Theou-Anton, Marie-Ange Massiani, Sylvie Friard, Boris Duchemann, Elizabeth Fabre, Etienne Giroux-Leprieur, Jacques Cadranel, Marie Wislez Cancers.2021; 13(20): 5132. CrossRef
Treatment Outcomes and Safety of Mobocertinib in Platinum-Pretreated Patients With EGFR Exon 20 Insertion–Positive Metastatic Non–Small Cell Lung Cancer Caicun Zhou, Suresh S. Ramalingam, Tae Min Kim, Sang-We Kim, James Chih-Hsin Yang, Gregory J. Riely, Tarek Mekhail, Danny Nguyen, Maria R. Garcia Campelo, Enriqueta Felip, Sylvie Vincent, Shu Jin, Celina Griffin, Veronica Bunn, Jianchang Lin, Huamao M. Li JAMA Oncology.2021; 7(12): e214761. CrossRef
A Real-World Study of Patients with Advanced Non-squamous Non-small Cell Lung Cancer with EGFR Exon 20 Insertion: Clinical Characteristics and Outcomes Christos Chouaid, Thomas Filleron, Didier Debieuvre, Maurice Pérol, Nicolas Girard, Eric Dansin, Hervé Lena, Radj Gervais, Sophie Cousin, Josiane Otto, Roland Schott, David Planchard, Anne Madroszyk, Courèche Kaderbhai, Pascale DUBRAY-Longeras, Sandrine H Targeted Oncology.2021; 16(6): 801. CrossRef
External Quality Assurance of Current Technology for the Testing of Cancer-Associated Circulating Free DNA Variants Sze Yee Chai, Rongxue Peng, Rui Zhang, Li Zhou, Nalishia Pillay, Kwang Hong Tay, Tony Badrick, Jinming Li, Martin P. Horan Pathology & Oncology Research.2020; 26(3): 1595. CrossRef
Osimertinib treatment for patients with EGFR exon 20 mutation positive non-small cell lung cancer B. van Veggel, J.F. Vilacha Madeira R Santos, S.M.S. Hashemi, M.S. Paats, K. Monkhorst, D.A.M. Heideman, M. Groves, T. Radonic, E.F. Smit, E. Schuuring, A.J. van der Wekken, A.J. de Langen Lung Cancer.2020; 141: 9. CrossRef
EGFR exon 20 insertion mutations in Chinese advanced non-small cell lung cancer patients: Molecular heterogeneity and treatment outcome from nationwide real-world study Guangjian Yang, Jun Li, Haiyan Xu, Yaning Yang, Lu Yang, Fei Xu, Bing Xia, Viola W. Zhu, Misako Nagasaka, Yan Yang, Yapin Li, Weini Qiu, Jianming Ying, Sai-Hong Ignatius Ou, Yan Wang Lung Cancer.2020; 145: 186. CrossRef
Variability of EGFR exon 20 insertions in 24 468 Chinese lung cancer patients and their divergent responses to EGFR inhibitors YanRu Qin, Hong Jian, Xiaoling Tong, Xue Wu, Fufeng Wang, Yang W. Shao, Xinmin Zhao Molecular Oncology.2020; 14(8): 1695. CrossRef
The effectiveness of afatinib in patients with lung adenocarcinoma harboring complex epidermal growth factor receptor mutation Shang-Gin Wu, Chong-Jen Yu, James Chih-Hsin Yang, Jin-Yuan Shih Therapeutic Advances in Medical Oncology.2020;[Epub] CrossRef
Spectrum of uncommon and compound epidermal growth factor receptor mutations in non-small-cell lung carcinomas with treatment response and outcome analysis: A study from India Varsha Singh, Aruna Nambirajan, Prabhat Singh Malik, Sanjay Thulkar, Ravindra Mohan Pandey, Kalpana Luthra, Sudheer Arava, Ruma Ray, Anant Mohan, Deepali Jain Lung Cancer.2020; 149: 53. CrossRef
Effectiveness of Treatments for Advanced Non–Small-Cell Lung Cancer With Exon 20 Insertion Epidermal Growth Factor Receptor Mutations Jenn-Yu Wu, Chong-Jen Yu, Jin-Yuan Shih Clinical Lung Cancer.2019; 20(6): e620. CrossRef
Clinical outcome of treatment of metastatic non-small cell lung cancer in patients harboring uncommon EGFR mutation J. Chantharasamee, N. Poungvarin, P. Danchaivijitr, S. Techawatanawanna BMC Cancer.2019;[Epub] CrossRef
Finding the Right Way to Target EGFR in Glioblastomas; Lessons from Lung Adenocarcinomas Ya Gao, Wies R. Vallentgoed, Pim J. French Cancers.2018; 10(12): 489. CrossRef
Purpose
Although it has been suggested that pulmonary tuberculosis (TB) is associated with increased risk of lung cancer, the exact mechanism is not clearly identified. We investigated the effect of pulmonary TB on the epidermal growth factor receptor (EGFR) mutational status and clinical outcome in patients with pulmonary adenocarcinoma.
Materials and Methods
We reviewed data of patients diagnosed with pulmonary adenocarcinoma harboring EGFR mutations and treated at our institution from 2008 to 2015. We divided our population into two groups: patients with pre-existing TB lesions on chest computed tomography scan (TB group) and those without the lesions (non-TB group). We compared the differences in EGFR mutational status, response to tyrosine kinase inhibitors (TKIs) and survival between the two groups.
Results
A total of 477 patients with pulmonary adenocarcinoma were analyzed. One hundred eighty-three patients (39%) had EGFR-mutated tumors and 100 (21%) patients had pre-existing TB lesions. The frequency of EGFR mutation was significantly higher in the TB group compared with the non-TB group (56% vs. 34%, p=0.038). Pre-existing TB lesions were independently associated with more frequent EGFR mutations in multivariate analysis (odds ratio, 1.43). In addition, both the progression-free survival (9.1 months vs. 11.6 months, p=0.020) and the overall survival (19.4 months vs. 24.5 months, p=0.014) after first-line EGFR-TKIs were significantly shorter in the TB group than in the non-TB group.
Conclusion
Previous pulmonary TB may be associated with more frequent EGFR mutations and poorer treatment response to EGFR-TKIs in patients with pulmonary adenocarcinoma.
Citations
Citations to this article as recorded by
A DNA Methylation Signature From Buccal Swabs to Identify Tuberculosis Infection Lovisa Karlsson, Isabelle Öhrnberg, Shumaila Sayyab, David Martínez-Enguita, Mika Gustafsson, Patricia Espinoza, Melissa Méndez-Aranda, Cesar Ugarte-Gil, Lameck Diero, Ronald Tonui, Jakob Paues, Maria Lerm The Journal of Infectious Diseases.2025; 231(1): e47. CrossRef
Progress in mechanism-based diagnosis and treatment of tuberculosis comorbid with tumor Chuan Wang, Rong-Qi Zou, Guo-Zhong He Frontiers in Immunology.2024;[Epub] CrossRef
Lung cancer and pulmonary tuberculosis: key features of molecular mechanisms of concomitant disease G. M. Agafonov, G. G. Kudriashov, U. S. Krylova, T. S. Zubareva, I. M. Kvetnoy, P. K. Yablonskiy Uspehi fiziologičeskih nauk.2024; 55(3): 58. CrossRef
Antimicrobial peptides as drugs with double response against Mycobacterium tuberculosis coinfections in lung cancer Giulia Polinário, Laura Maria Duran Gleriani Primo, Maiara Alane Baraldi Cerquetani Rosa, Freddy Humberto Marin Dett, Paula Aboud Barbugli, Cesar Augusto Roque-Borda, Fernando Rogério Pavan Frontiers in Microbiology.2023;[Epub] CrossRef
Prevalence of Lung Cancer with a History of Tuberculosis Nadira Putri Nastiti, Laksmi Wulandari, Sulistiawati Sulistiawati, Anna Febriani, Wiwin Is Effendi Jurnal Respirasi.2023; 9(2): 87. CrossRef
Previous pulmonary tuberculosis enhances the risk of lung cancer: systematic reviews and meta-analysis Hossein Abdeahad, Maryam Salehi, Atieh Yaghoubi, Amir Hossein Aalami, Farnoosh Aalami, Saman Soleimanpour Infectious Diseases.2022; 54(4): 255. CrossRef
Pulmonary Tuberculosis and Risk of Lung Cancer: A Systematic Review and Meta-Analysis Soo Young Hwang, Jong Yeob Kim, Hye Sun Lee, Sujee Lee, Dayeong Kim, Subin Kim, Jong Hoon Hyun, Jae Il Shin, Kyoung Hwa Lee, Sang Hoon Han, Young Goo Song Journal of Clinical Medicine.2022; 11(3): 765. CrossRef
Clinical and pathological characteristics associated with the presence of the IS6110 Mycobacterim tuberculosis transposon in neoplastic cells from non-small cell lung cancer patients Oscar Arrieta, Camilo Molina-Romero, Fernanda Cornejo-Granados, Brenda Marquina-Castillo, Alejandro Avilés-Salas, Gamaliel López-Leal, Andrés F. Cardona, Alette Ortega-Gómez, Mario Orozco-Morales, Adrián Ochoa-Leyva, Rogelio Hernandez-Pando Scientific Reports.2022;[Epub] CrossRef
Lung cancer occurrence after an episode of tuberculosis: a systematic review and meta-analysis Javier Cabrera-Sanchez, Vicente Cuba, Victor Vega, Patrick Van der Stuyft, Larissa Otero European Respiratory Review.2022; 31(165): 220025. CrossRef
Proteomic profile of vitreous in patients with tubercular uveitis Reema Bansal, Mohd M. Khan, Surendra Dasari, Indu Verma, David R. Goodlett, Nathan P. Manes, Aleksandra Nita-Lazar, Surya P. Sharma, Aman Kumar, Nirbhai Singh, Anuradha Chakraborti, Vishali Gupta, M.R. Dogra, Jagat Ram, Amod Gupta Tuberculosis.2021; 126: 102036. CrossRef
Epidermal growth factor receptor-mutant pulmonary adenocarcinoma coexisting with tuberculosis Ning Liu, Lingnan Zheng, Min Yu, Shuang Zhang Medicine.2021; 100(8): e24569. CrossRef
Quantitative analysis of cell-free DNA by droplet digital PCR reveals the presence of EGFR mutations in non-malignant lung pathologies Rajesh Venkataram, Srividya Arjuna, Giridhar Belur Hosmane, Anirban Chakraborty Monaldi Archives for Chest Disease.2021;[Epub] CrossRef
Concomitant Pulmonary Tuberculosis Impair Survival in Advanced Epidermal Growth Factor Receptor (EGFR) Mutant Lung Adenocarcinoma Patients Receiving EGFR-Tyrosine Kinase Inhibitor Yalin Xie, Ning Su, Wei Zhou, An Lei, Xiang Li, Weiwei Li, Zhan Huang, Wenchang Cen, Jinxing Hu Cancer Management and Research.2021; Volume 13: 7517. CrossRef
A Case of Delayed Diagnostic Pulmonary Tuberculosis during Targeted Therapy in an EGFR Mutant Non-Small Cell Lung Cancer Patient Caibao Jin, Bin Yang Case Reports in Oncology.2021; 14(1): 659. CrossRef
Follow‐up of an occult tuberculosis scar cancer after resection of metastatic lesions Mengyao Sun, Yinghui Xu, Xu Wang, Chao Sun, Ye Guo, Guoguang Shao, Zhiguang Yang, Yunpeng Liu, Peng Zhang, Shi Qiu, Kewei Ma Thoracic Cancer.2020; 11(8): 2347. CrossRef
Purpose
Malignant pleural effusions (MPEs) are often observed in lung cancer, particularly adenocarcinoma. The aim of this study was to investigate epidermal growth factor receptor (EGFR) mutation status in lung adenocarcinoma-associated MPEs (LA-MPEs) and its correlation with efficacy of EGFR tyrosine kinase inhibitor (TKI) therapy.
Materials and Methods
Samples comprised 40 cell blocks of pathologically-confirmed LA-MPEs collected before the start of EGFR TKI therapy. EGFR mutation status was re-evaluated by peptide nucleic acid clamping and the clinical outcomes of EGFR TKI‒treated patients were analyzed retrospectively.
Results EGFR mutations were detected in 72.5% of LA-MPE cell blocks (29/40). The median progression-free survival for patients with EGFR mutations in LA-MPEs was better than that for patients with wild-type EGFR (7.33 months vs. 2.07 months; hazard ratio, 0.486; 95% confidence interval, 0.206 to 1.144; p=0.032). The objective response rate (ORR) of 26 patients with EGFR mutations in LA-MPEs among the 36 patients with measurable lesions was 80.8%, while the ORR of the 10 patients with wild-type EGFR in LA-MPEs was 10% (p < 0.001). Among the 26 patients with EGFR mutations in LA-MPEs, the ORR of target lesions and LA-MPEs were 88.5% and 61.5%, respectively (p=0.026).
Conclusion EGFR mutation status in cell blocks of LA-MPEs confirmed by pathologic diagnosis is highly predictive of EGFR TKI efficacy. For patients with EGFR mutations in LA-MPEs, the response to EGFR TKIs seems to be worse for pleural effusions than for solid tumors.
Effect of chemotherapy, immunotherapy, and targeted therapies on removal of indwelling pleural catheters in non-small cell lung cancer patients with malignant pleural effusions Melissa Wang, Kaitlin Sparrow, Chrystal Chan, Ashley Gillson, Daniel Stollery, Pen Li Respiratory Medicine.2023; 206: 107093. CrossRef
Malignant pleural effusion diagnosis and therapy Liangliang Yang, Yue Wang Open Life Sciences.2023;[Epub] CrossRef
Failure pattern and radiotherapy exploration in malignant pleural effusion non-small cell lung cancer treated with targeted therapy Qingsong Li, Cheng Hu, Shengfa Su, Zhu Ma, Yichao Geng, Yinxiang Hu, Huiqin Li, Bing Lu Frontiers in Oncology.2023;[Epub] CrossRef
Impact of thoracic tumor radiotherapy on survival in non‐small‐cell lung cancer with malignant pleural effusion treated with targeted therapy: Propensity score matching study Qingsong Li, Cheng Hu, Shengfa Su, Zhu Ma, Yichao Geng, Yinxiang Hu, Haijie Jin, Huiqin Li, Bing Lu Cancer Medicine.2023; 12(14): 14949. CrossRef
EGFR Mutation is a Prognostic Factor in Lung Cancer Patients with Pleural Dissemination Detected During or After Surgery Toshiya Fujiwara, Kazuhiko Shien, Motoki Matsuura, Junichi Soh, Hiromasa Yamamoto, Soshi Takao, Yuho Maki, Tsuyoshi Ueno, Ryujiro Sugimoto, Ken Suzawa, Mikio Okazaki, Hiroyuki Tao, Makio Hayama, Masafumi Kataoka, Yoshifumi Sano, Hidetoshi Inokawa, Motohir Annals of Surgical Oncology.2023; 30(11): 6697. CrossRef
Efficacy of hyperthermic intrathoracic chemotherapy for initially diagnosed lung cancer with symptomatic malignant pleural effusion Zihui Li, Jie Deng, Fei Yan, Li Liu, Yanling Ma, Jianhai Sun Scientific Reports.2023;[Epub] CrossRef
Establishment of prognostic nomograms for predicting the progression free survival of EGFR‐sensitizing mutation, advanced lung cancer patients treated with EGFR‐TKIs Xinyang Du, Hua Bai, Zhijie Wang, Jianchun Daun, Zheng Liu, Jiachen Xu, Geyun Chang, Yixiang Zhu, Jie Wang Thoracic Cancer.2022; 13(9): 1289. CrossRef
Clinical features and prognosis according to genomic mutations in primary and metastatic lesions of non‐small‐cell lung cancer Wei Zhang, Wenjuan Han, Bo Yu, Xin Zhao, Gaojun Lu, Wendy Wu, Yi Zhang Thoracic Cancer.2022; 13(11): 1642. CrossRef
Management of Malignant Pleural Effusion: Where Are We Now? Julien Guinde, Hervé Dutau, Philippe Astoul Seminars in Respiratory and Critical Care Medicine.2022; 43(04): 559. CrossRef
Non-Small Cell Lung Cancer with Malignant Pleural Effusion May Require Primary Tumor Radiotherapy in Addition to Drug Treatment Qingsong Li, Cheng Hu, Shengfa Su, Zhu Ma, Yichao Geng, Yinxiang Hu, Huiqin Li, Bing Lu Cancer Management and Research.2022; Volume 14: 3347. CrossRef
The impact of smoking status on the progression‐free survival of non‐small cell lung cancer patients receiving molecularly target therapy or immunotherapy versus chemotherapy: A meta‐analysis Xinyi Li, Cong Huang, Xiaohui Xie, Ziyang Wu, Xia Tian, Yibo Wu, Xin Du, Luwen Shi Journal of Clinical Pharmacy and Therapeutics.2021; 46(2): 256. CrossRef
Risk Factors for and Time to Recurrence of Symptomatic Malignant Pleural Effusion in Patients With Metastatic Non-Small Cell Lung Cancer with EGFR or ALK Mutations Audra J. Schwalk, David E. Ost, Sahara N. Saltijeral, Henriette De La Garza, Roberto F. Casal, Carlos A. Jimenez, Georgie A. Eapen, Jeff Lewis, Waree Rinsurongkawong, Vadeerat Rinsurongkawong, Jack Lee, Yasir Elamin, Jianjun Zhang, Jack A. Roth, Stephen S Chest.2021; 159(3): 1256. CrossRef
Advances in pleural infection and malignancy Eihab O. Bedawi, Julien Guinde, Najiib M. Rahman, Philippe Astoul European Respiratory Review.2021; 30(159): 200002. CrossRef
Diving into the Pleural Fluid: Liquid Biopsy for Metastatic Malignant Pleural Effusions Maria Alba Sorolla, Anabel Sorolla, Eva Parisi, Antonieta Salud, José M. Porcel Cancers.2021; 13(11): 2798. CrossRef
Clinical Characteristics and Therapeutic Outcomes of Metastatic Peritoneal Carcinomatosis in Non-Small-Cell Lung Cancer Tetsuo Tani, Ichiro Nakachi, Shinnosuke Ikemura, Shigenari Nukaga, Keiko Ohgino, Aoi Kuroda, Hideki Terai, Keita Masuzawa, Taro Shinozaki, Kota Ishioka, Yohei Funatsu, Hidefumi Koh, Koichi Fukunaga, Kenzo Soejima Cancer Management and Research.2021; Volume 13: 7497. CrossRef
LENT Score: Predicting the Survival of Malignant Pleural Effusion – A Prospective Study of Three Years Sara Raimundo, Ana Isabel Loureiro, Fortunato Vieira, Ana Fernandes Archivos de Bronconeumología.2020; 56(7): 465. CrossRef
Current applications of molecular testing on body cavity fluids Daniel Pinto, Fernando Schmitt Diagnostic Cytopathology.2020; 48(9): 840. CrossRef
Gene Alterations in Paired Supernatants and Precipitates from Malignant Pleural Effusions of Non-Squamous Non-Small Cell Lung Cancer Jianqiang Li, Xingliang Li, Wenxian Wang, Yang Shao, Yiping Zhang, Zhengbo Song Translational Oncology.2020; 13(8): 100784. CrossRef
Progression of malignant pleural effusion during the early stage of gefitinib treatment in advanced EGFR-mutant lung adenocarcinoma involving complex driver gene mutations Ning Liu, Min Yu, Tao Yin, Yong Jiang, Xuelian Liao, Jie Tang, Yanying Li, Diyuan Qin, Dan Li, Yongsheng Wang Signal Transduction and Targeted Therapy.2020;[Epub] CrossRef
LENT Score: Predicting the Survival of Malignant Pleural Effusion – A Prospective Study of Three Years Sara Raimundo, Ana Isabel Loureiro, Fortunato Vieira, Ana Fernandes Archivos de Bronconeumología (English Edition).2020; 56(7): 465. CrossRef
Recent Developments in the Management of Malignant Pleural Effusions: a Narrative Review Clifford E. Coile, Jessie G. Harvey, Michal Senitko Current Pulmonology Reports.2020; 9(4): 164. CrossRef
Detecting EGFR mutations and ALK/ROS1 rearrangements in non‐small cell lung cancer using malignant pleural effusion samples Yi Yao, Min Peng, Qinglin Shen, Qinyong Hu, Hongyun Gong, Qingqing Li, Zhongliang Zheng, Bin Xu, Yingge Li, Yi Dong Thoracic Cancer.2019; 10(2): 193. CrossRef
Making cold malignant pleural effusions hot: driving novel immunotherapies Pranav Murthy, Chigozirim N. Ekeke, Kira L. Russell, Samuel C. Butler, Yue Wang, James D. Luketich, Adam C. Soloff, Rajeev Dhupar, Michael T. Lotze OncoImmunology.2019; 8(4): e1554969. CrossRef
Novel insights into the systemic treatment of lung cancer malignant pleural effusion Claire Tissot, Pierre Gay, Clément Brun, Marios E. Froudarakis The Clinical Respiratory Journal.2019; 13(3): 131. CrossRef
Proceedings of the American Society of Cytopathology companion session at the 2019 United States and Canadian Academy of Pathology Annual meeting, part 2: effusion cytology with focus on theranostics and diagnosis of malignant mesothelioma Momin T. Siddiqui, Fernando Schmitt, Andrew Churg Journal of the American Society of Cytopathology.2019; 8(6): 352. CrossRef
Purpose
The study investigated whether a replacement of neutrophil count and platelet count by neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) within the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) model would improve its prognostic accuracy.
Materials and Methods
This retrospective analysis included consecutive patients with metastatic renal cell carcinoma treated with first-line tyrosine kinase inhibitors. The IMDC and modified-IMDC models were compared using: concordance index (CI), bias-corrected concordance index (BCCI), calibration plots, the Grønnesby and Borgan test, Bayesian Information Criterion (BIC), generalized R2, Integrated Discrimination Improvement (IDI), and continuous Net Reclassification Index (cNRI) for individual risk factors and the three risk groups.
Results
Three hundred and twenty-one patients were eligible for analyses. The modified-IMDC model with NLR value of 3.6 and PLR value of 157 was selected for comparison with the IMDC model. Both models were well calibrated. All other measures favoured the modified-IMDC model over the IMDC model (CI, 0.706 vs. 0.677; BCCI, 0.699 vs. 0.671; BIC, 2,176.2 vs. 2,190.7; generalized R2, 0.238 vs. 0.202; IDI, 0.044; cNRI, 0.279 for individual risk factors; and CI, 0.669 vs. 0.641; BCCI, 0.669 vs. 0.641; BIC, 2,183.2 vs. 2,198.1; generalized R2, 0.163 vs. 0.123; IDI, 0.045; cNRI, 0.165 for the three risk groups).
Conclusion
Incorporation of NLR and PLR in place of neutrophil count and platelet count improved prognostic accuracy of the IMDC model. These findings require external validation before introducing into clinical practice.
Citations
Citations to this article as recorded by
Correlation of Prognostic Nutritional Index and Systemic Immune-Inflammation Index with the Recurrence and Prognosis in Oral Squamous Cell Carcinoma with the Stage of III/IV Manjun Ye, Lixia Zhang International Journal of General Medicine.2024; Volume 17: 2289. CrossRef
Evaluating the Prognostic Variables for Overall Survival in Patients with Metastatic Renal Cell Carcinoma: A Meta-Analysis Of 29,366 Patients Bruce Li, Swati Sood, Melissa J. Huynh, Nicholas E. Power JU Open Plus.2024;[Epub] CrossRef
The relationship between complete blood cell count-derived inflammatory biomarkers and benign prostatic hyperplasia in middle-aged and elderly individuals in the United States: Evidence from NHANES 2001–2008 Chengdong Shi, Hongliang Cao, Guoqiang Zeng, Lei Yang, Yuantao Wang, Alaa A. A. Aljabali PLOS ONE.2024; 19(7): e0306860. CrossRef
Evaluation of prognostic factors for late recurrence in clear cell renal carcinoma: an institutional study Diana Voskuil-Galoş, Tudor Călinici, Andra Piciu, Adina Nemeş Frontiers in Oncology.2024;[Epub] CrossRef
Plasma carnitine, choline, γ-butyrobetaine, and trimethylamine-N-oxide, but not zonulin, are reduced in overweight/obese patients with pre/diabetes or impaired glycemia Alia Snouper, Violet Kasabri, Nailya Bulatova, Maysa Suyagh, Monther Sadder, Khaldoun Shnewer, Ismail Yousef International Journal of Diabetes in Developing Countries.2023; 43(4): 592. CrossRef
Artificial intelligence-based prediction of overall survival in metastatic renal cell carcinoma Ella Barkan, Camillo Porta, Simona Rabinovici-Cohen, Valentina Tibollo, Silvana Quaglini, Mimma Rizzo Frontiers in Oncology.2023;[Epub] CrossRef
The Prognostic Value of Neutrophil-to-Lymphocyte Ratio and Platelet-to-Lymphocyte Ratio for Small Renal Cell Carcinomas after Image-Guided Cryoablation or Radio-Frequency Ablation Aqua Asif, Vinson Wai-Shun Chan, Filzah Hanis Osman, Jasmine Sze-Ern Koe, Alexander Ng, Oliver Edward Burton, Jon Cartledge, Michael Kimuli, Naveen Vasudev, Christy Ralph, Satinder Jagdev, Selina Bhattarai, Jonathan Smith, James Lenton, Tze Min Wah Cancers.2023; 15(7): 2187. CrossRef
A meta-analysis of the platelet-lymphocyte ratio: A notable prognostic factor in renal cell carcinoma Xiao Zhou, Guangcheng Luo The International Journal of Biological Markers.2022; 37(2): 123. CrossRef
Prognostic Role of Systemic Inflammatory Markers in Patients Undergoing Surgical Resection for Oral Squamous Cell Carcinoma Uiju Cho, Yeoun-Eun Sung, Min-Sik Kim, Youn-Soo Lee Biomedicines.2022; 10(6): 1268. CrossRef
Prognostic value of glucose to lymphocyte ratio for patients with renal cell carcinoma undergoing laparoscopic nephrectomy: A multi-institutional, propensity score matching cohort study Jinliang Ni, Ziye Li, Wei Song, Houliang Zhang, Yidi Wang, Yifan Zhang, Haipeng Zhang, Guangcan Yang, Jun Xie, Keyi Wang, Bo Peng, Weipu Mao Frontiers in Surgery.2022;[Epub] CrossRef
Associations between Pretreatment Body Composition Features and Clinical Outcomes among Patients with Metastatic Clear Cell Renal Cell Carcinoma Treated with Immune Checkpoint Blockade Yasser Ged, Alejandro Sanchez, Sujata Patil, Andrea Knezevic, Emily Stein, Stacey Petruzella, Kate Weiss, Cihan Duzgol, Joshua Chaim, Oguz Akin, Marina Mourtzakis, Michael T. Paris, Jessica Scott, Fengshen Kuo, Ritesh Kotecha, A. Ari Hakimi, Chung-Han Lee Clinical Cancer Research.2022; 28(23): 5180. CrossRef
Exploratory Analysis of the Platelet-to-Lymphocyte Ratio Prognostic Value in the Adjuvant Renal Cell Cancer Setting Anup Patel, Alain Ravaud, Robert J Motzer, Allan J Pantuck, Michael Staehler, Bernard Escudier, Jean-François Martini, Mariajose Lechuga, Xun Lin, Daniel J George Future Oncology.2021; 17(4): 403. CrossRef
Preoperative anaemia and thrombocytosis predict adverse prognosis in non‐metastatic renal cell carcinoma with tumour thrombus Ruotao Xiao, Chuxiao Xu, Wei He, Lei Liu, Hongxian Zhang, Cheng Liu, Lulin Ma BMC Urology.2021;[Epub] CrossRef
Real-World Outcomes in Patients with Metastatic Renal Cell Carcinoma According to Risk Factors: The STAR-TOR Registry Arne Strauss, Marianne Schmid, Michael Rink, Michael Moran, Stephan Bernhardt, Marcus Hubbe, Lothar Bergmann, Katrin Schlack, Martin Boegemann Future Oncology.2021; 17(18): 2325. CrossRef
Systemic Inflammation Response Index is an Independent Prognostic Indicator for Patients with Renal Cell Carcinoma Undergoing Laparoscopic Nephrectomy: A Multi-Institutional Cohort Study Weipu Mao, Si Sun, Ting He, Xin Jin, Jianping Wu, Bin Xu, Guangyuan Zhang, Keyi Wang, Ming Chen Cancer Management and Research.2021; Volume 13: 6437. CrossRef
Can Systemic Immune-Inflammation Index Create a New Perspective for the IMDC Scoring System in Patients with Metastatic Renal Cell Carcinoma? Fatma Bugdayci Basal, Cengiz Karacin, Irem Bilgetekin, Omur Berna Oksuzoglu Urologia Internationalis.2021; 105(7-8): 666. CrossRef
Post-surgical Regression of Thoracic Metastases After Salvage Lobectomy for Recurrent Renal Cell Carcinoma Alessia Stanzi, Elena Verzoni, Margherita Ruggirello, Luigi Rolli, Ugo Pastorino Clinical Genitourinary Cancer.2020; 18(3): e284. CrossRef
Peking University Third Hospital score: a comprehensive system to predict intra-operative blood loss in radical nephrectomy and thrombectomy Zhuo Liu, Xun Zhao, Hong-Xian Zhang, Run-Zhuo Ma, Li-Wei Li, Shi-Ying Tang, Guo-Liang Wang, Shu-Dong Zhang, Shu-Min Wang, Xiao-Jun Tian, Lu-Lin Ma Chinese Medical Journal.2020; 133(10): 1166. CrossRef
Prognostic Value of Systemic Inflammatory Biomarkers in Patients with Metastatic Renal Cell Carcinoma Guilherme Nader Marta, Pedro Isaacsson Velho, Renata R. C. Bonadio, Mirella Nardo, Sheila F. Faraj, Manoel Carlos L. de Azevedo Souza, David Q. B. Muniz, Diogo Assed Bastos, Carlos Dzik Pathology & Oncology Research.2020; 26(4): 2489. CrossRef
The Clinical Significance of Routine Risk Categorization in Metastatic Renal Cell Carcinoma and its Impact on Treatment Decision-Making: A Systematic Review Shouki Bazarbashi, Abdullah Alsharm, Faisal Azam, Hazem El Ashry, Jamal Zekri Future Oncology.2020; 16(34): 2879. CrossRef
Patient selection and risk factors in the changing treatment landscape of metastatic renal cell carcinoma Ehab Abdou, Ravi M. Pedapenki, Mohamed Abouagour, Abdul R. Zar, Emad Dawoud, Dalia Elshourbagy, Humaid O. Al-Shamsi, Enrique Grande Expert Review of Anticancer Therapy.2020; 20(10): 831. CrossRef
Neutrophil-to-Lymphocyte Ratio as a Prognostic Factor of Disease-free Survival in Postnephrectomy High-risk Locoregional Renal Cell Carcinoma: Analysis of the S-TRAC Trial Anup Patel, Alain Ravaud, Robert J. Motzer, Allan J. Pantuck, Michael Staehler, Bernard Escudier, Jean-François Martini, Mariajose Lechuga, Xun Lin, Daniel J. George Clinical Cancer Research.2020; 26(18): 4863. CrossRef
External validation of the systemic immune-inflammation index as a prognostic factor in metastatic renal cell carcinoma and its implementation within the international metastatic renal cell carcinoma database consortium model Pawel Chrom, Jakub Zolnierek, Lubomir Bodnar, Rafal Stec, Cezary Szczylik International Journal of Clinical Oncology.2019; 24(5): 526. CrossRef
Assessing Outcomes and Prognostic Factors for First-Line Therapy in Elderly Patients With Metastatic Renal Cell Carcinoma: Real-Life Data From a Single United Kingdom Institution Mario Uccello, Tasnim Alam, Haider Abbas, Ajith Nair, Jennifer Paskins, Guy Faust Clinical Genitourinary Cancer.2019; 17(3): e658. CrossRef
Towards individualized therapy for metastatic renal cell carcinoma Ritesh R. Kotecha, Robert J. Motzer, Martin H. Voss Nature Reviews Clinical Oncology.2019; 16(10): 621. CrossRef
The impact of neutrophil-to-lymphocyte, platelet-to-lymphocyte and haemoglobin-to-platelet ratio on localised renal cell carcinoma oncologic outcomes S. Albisinni, D. Pretot, W. Al Hajj Obeid, F. Aoun, T. Quackels, A. Peltier, T. Roumeguère Progrès en Urologie.2019; 29(8-9): 423. CrossRef
Prognostic Significance of Systemic Inflammatory Response in Patients with Synchronous and Metachronous Metastatic Renal Cell Carcinoma Receiving First-Line Tyrosine Kinase Inhibitors Joongwon Choi, Tae Jin Kim, Hyun Hwan Sung, Hwang Gyun Jeon, Byong Chang Jeong, Seong Soo Jeon, Hyun Moo Lee, Han Yong Choi, Minyong Kang, Seong Il Seo The Korean Journal of Urological Oncology.2019; 17(3): 150. CrossRef
The Role of Neutrophil-Lymphocyte Ratio, Platelet-Lymphocyte Ratio, and Platelets in the Prognosis of Metastatic Renal Cell Carcinoma Joanna Huszno, Zofia Kolosza, Jolanta Mrochem-Kwarciak, Tomasz Rutkowski, Krzysztof Skladowski Oncology.2019; 97(1): 7. CrossRef
Platelet-to-lymphocyte ratio in advanced Cancer: Review and meta-analysis Bo Li, Pingting Zhou, Yujie Liu, Haifeng Wei, Xinghai Yang, Tianrui Chen, Jianru Xiao Clinica Chimica Acta.2018; 483: 48. CrossRef
Combined neutrophil/platelet/lymphocyte/differentiation score predicts chemosensitivity in advanced gastric cancer Zhenhua Huang, Yantan Liu, Chen Yang, Xiaoyin Li, Changqie Pan, Jinjun Rao, Nailin Li, Wangjun Liao, Li Lin BMC Cancer.2018;[Epub] CrossRef
The clinical use of the platelet to lymphocyte ratio and lymphocyte to monocyte ratio as prognostic factors in renal cell carcinoma: a systematic review and meta-analysis Xuemin Wang, Shiqiang Su, Yuanshan Guo Oncotarget.2017; 8(48): 84506. CrossRef
Purpose
This phase II study examined whether the addition of simvastatin to afatinib provides a clinical benefit compared with afatinib monotherapy in previously treated patients with nonadenocarcinomatous non-small cell lung cancer (NA-NSCLC).
Materials and Methods
Patientswith advancedNA-NSCLCwho progressed after one ortwo chemotherapy regimens were randomly assigned to a simvastatin (40 mg/day) plus afatinib (40 mg/day) (AS) arm or to an afatinib (A) arm. The primary endpoint was response rate (RR).
Results
Sixty-eight patients were enrolled (36 in the AS arm and 32 in the A arm). The RR was 5.7% (95% confidence interval [CI], 0.7 to 19.2) for AS and 9.4% (95% CI, 2.0 to 25.0) for A (p=0.440). In arms AS and A, the median progression-free survival (PFS) was 1.0 versus 3.6 months (p=0.240) and the overall survival was 10.0 months versus 7.0 months (p=0.930), respectively. Skin rash, stomatitis, and diarrhea were the most common adverse events in both arms. More grade 3 or 4 diarrhea was observed in arm A (18.8% vs. 5.6% in arm AS). In all patients, the median PFS for treatment including afatinib was not correlated with the status of epidermal growth factor receptor (EGFR) mutation (p=0.122), EGFR fluorescence in situ hybridization (p=0.944), or EGFR immunohistochemistry (p=0.976). However, skin rash severity was significantly related to the risk of progression for afatinib (hazard ratio for skin rash grade ≥ 2 vs. grade < 2, 0.44; 95% CI, 0.25 to 0.78; p=0.005).
Conclusion
There were no significant differences in the efficacy between AS and A arms in patients with NA-NSCLC.
Citations
Citations to this article as recorded by
Statins in the Cause and Prevention of Cancer: Confounding by Indication and Mediation by Rhabdomyolysis and Phosphate Toxicity Ronald B. Brown Journal of Cardiovascular Development and Disease.2024; 11(9): 296. CrossRef
Unraveling lipid metabolism reprogramming for overcoming drug resistance in melanoma Ruilong Wang, Qin Yan, Xiao Liu, Jinfeng Wu Biochemical Pharmacology.2024; 223: 116122. CrossRef
Cardiovascular/anti‐inflammatory drugs repurposed for treating or preventing cancer: A systematic review and meta‐analysis of randomized trials David J. Benjamin, Alyson Haslam, Vinay Prasad Cancer Medicine.2024;[Epub] CrossRef
The preventative effects of statin on lung cancer development in patients with idiopathic pulmonary fibrosis using the National Health Insurance Service Database in Korea Yoo Jung Lee, Nayoon Kang, Junghyun Nam, Eung Gu Lee, Jiwon Ryoo, Soon Seog Kwon, Yong Hyun Kim, Hye Seon Kang, Tsai-Ching Hsu PLOS ONE.2024; 19(3): e0299484. CrossRef
DHCR24 in Tumor Diagnosis and Treatment: A Comprehensive Review Xin Fu, Zhaosong Wang Technology in Cancer Research & Treatment.2024;[Epub] CrossRef
β-blockers and statins: exploring the potential off-label applications in breast, colorectal, prostate, and lung cancers Pedro Gabriel Senger Braga, Janaína da Silva Vieira, Aline Rachel Bezerra Gurgel, Patricia Chakur Brum Frontiers in Pharmacology.2024;[Epub] CrossRef
The effects of statins in patients with advanced-stage cancers - a systematic review and meta-analysis Qiang Zhou, Zhihua Jiao, Yuxi Liu, Peter N. Devreotes, Zhenyu Zhang Frontiers in Oncology.2023;[Epub] CrossRef
Assessment in vitro of interactions between anti-cancer drugs and noncancer drugs commonly used by cancer patients Claes R. Andersson, Jiawei Ye, Kristin Blom, Mårten Fryknäs, Rolf Larsson, Peter Nygren Anti-Cancer Drugs.2023; 34(1): 92. CrossRef
New insights into the therapeutic potentials of statins in cancer Chengyu Liu, Hong Chen, Bicheng Hu, Jiajian Shi, Yuchen Chen, Kun Huang Frontiers in Pharmacology.2023;[Epub] CrossRef
Functional significance of cholesterol metabolism in cancer: from threat to treatment Mingming Xiao, Jin Xu, Wei Wang, Bo Zhang, Jiang Liu, Jialin Li, Hang Xu, Yingjun Zhao, Xianjun Yu, Si Shi Experimental & Molecular Medicine.2023; 55(9): 1982. CrossRef
Simvastatin Enhanced Anti-tumor Effects of Bevacizumab against Lung Adenocarcinoma
A549 Cells via Abating HIF-1α-Wnt/β-Catenin Signaling Pathway Xin Tu, Jian Zhang, Wei Yuan, Xia Wu, Zhi Xu, Cuo Qing Anti-Cancer Agents in Medicinal Chemistry.2023; 23(19): 2083. CrossRef
Lipoproteins and cancer: The role of HDL-C, LDL-C, and cholesterol-lowering drugs Kush K. Patel, Khosrow Kashfi Biochemical Pharmacology.2022; 196: 114654. CrossRef
Beyond Lipid-Lowering: Effects of Statins on Cardiovascular and Cerebrovascular Diseases and Cancer Yoichi Morofuji, Shinsuke Nakagawa, Kenta Ujifuku, Takashi Fujimoto, Kaishi Otsuka, Masami Niwa, Keisuke Tsutsumi Pharmaceuticals.2022; 15(2): 151. CrossRef
Reprogramming of Lipid Metabolism in Lung Cancer: An Overview with Focus on EGFR-Mutated Non-Small Cell Lung Cancer Kamal Eltayeb, Silvia La Monica, Marcello Tiseo, Roberta Alfieri, Claudia Fumarola Cells.2022; 11(3): 413. CrossRef
Effect of Statins on Lung Cancer Molecular Pathways: A Possible Therapeutic Role Gianmarco Marcianò, Caterina Palleria, Alessandro Casarella, Vincenzo Rania, Emanuele Basile, Luca Catarisano, Cristina Vocca, Luigi Bianco, Corrado Pelaia, Erika Cione, Bruno D’Agostino, Rita Citraro, Giovambattista De Sarro, Luca Gallelli Pharmaceuticals.2022; 15(5): 589. CrossRef
The effects of epithelial–mesenchymal transitions in COPD induced by cigarette smoke: an update Xiaoshan Su, Weijing Wu, Zhixing Zhu, Xiaoping Lin, Yiming Zeng Respiratory Research.2022;[Epub] CrossRef
Scientific Research Directions on the Histopathology and Immunohistochemistry of the Cutaneous Squamous Cell Carcinoma: A Scientometric Study Iuliu Gabriel Cocuz, Maria Elena Cocuz, Angela Repanovici, Adrian-Horațiu Sabău, Raluca Niculescu, Andreea-Cătălina Tinca, Vlad Vunvulea, Corina Eugenia Budin, Andreea Raluca Szoke, Maria Cătălina Popelea, Raluca Moraru, Titiana Cornelia Cotoi, Ovidiu Sim Medicina.2022; 58(10): 1449. CrossRef
Lipid metabolism and cancer Xueli Bian, Rui Liu, Ying Meng, Dongming Xing, Daqian Xu, Zhimin Lu Journal of Experimental Medicine.2021;[Epub] CrossRef
Simvastatin-romidepsin combination kills bladder cancer cells synergistically Kazuki Okubo, Kosuke Miyai, Kimi Kato, Takako Asano, Akinori Sato Translational Oncology.2021; 14(9): 101154. CrossRef
Statins Decrease Programmed Death-Ligand 1 (PD-L1) by Inhibiting AKT and β-Catenin Signaling Woo-Jin Lim, Mingyu Lee, Yerin Oh, Xue-Quan Fang, Sujin Lee, Chang-Hoon Lim, Jooho Park, Ji-Hong Lim Cells.2021; 10(9): 2488. CrossRef
ABL allosteric inhibitors synergize with statins to enhance apoptosis of metastatic lung cancer cells Jillian Hattaway Luttman, Jacob P. Hoj, Kevin H. Lin, Jiaxing Lin, Jing Jin Gu, Clay Rouse, Amanda G. Nichols, Nancie J. MacIver, Kris C. Wood, Ann Marie Pendergast Cell Reports.2021; 37(4): 109880. CrossRef
Adjuvant statin therapy for oesophageal adenocarcinoma: the STAT-ROC feasibility study L. Alexandre, A. B. Clark, S. Walton, M. P. Lewis, B. Kumar, E. C. Cheong, H. Warren, S. S. Kadirkamanathan, S. L. Parsons, S. M. Dresner, E. Sims, M. Jones, M. Hammond, M. Flather, Y. K. Loke, A. M. Swart, A. R. Hart BJS Open.2020; 4(1): 59. CrossRef
Whether statin use improves the survival of patients with glioblastoma? Yonglin Xie, Qin Lu, Cameron Lenahan, Shuxu Yang, Daoyang Zhou, Xuchen Qi Medicine.2020; 99(9): e18997. CrossRef
Fluvastatin potentiates anticancer activity of vorinostat in renal cancer cells Kazuki Okubo, Makoto Isono, Kosuke Miyai, Takako Asano, Akinori Sato Cancer Science.2020; 111(1): 112. CrossRef
Repurposing of drugs approved for cardiovascular diseases: Opportunity or mirage? Paolo Gelosa, Laura Castiglioni, Marina Camera, Luigi Sironi Biochemical Pharmacology.2020; 177: 113895. CrossRef
Attenuation of the pro-inflammatory signature of lung cancer-derived mesenchymal stromal cells by statins Sabine Galland, Patricia Martin, Giulia Fregni, Igor Letovanec, Ivan Stamenkovic Cancer Letters.2020; 484: 50. CrossRef
Efficacy and safety profile of statins in patients with cancer: a systematic review of randomised controlled trials John P. Thomas, Yoon K. Loke, Leo Alexandre European Journal of Clinical Pharmacology.2020; 76(12): 1639. CrossRef
Statins as Anticancer Agents in the Era of Precision Medicine Joseph Longo, Jenna E. van Leeuwen, Mohamad Elbaz, Emily Branchard, Linda Z. Penn Clinical Cancer Research.2020; 26(22): 5791. CrossRef
Dipyridamole Enhances the Cytotoxicities of Trametinib against Colon Cancer Cells through Combined Targeting of HMGCS1 and MEK Pathway Sheng Zhou, Huanji Xu, Qiulin Tang, Hongwei Xia, Feng Bi Molecular Cancer Therapeutics.2020; 19(1): 135. CrossRef
Repurposed Drugs Trials by Cancer Type Joseph C. Murray, Benjamin Levy The Cancer Journal.2019; 25(2): 127. CrossRef
Diverse Stakeholders of Tumor Metabolism: An Appraisal of the Emerging Approach of Multifaceted Metabolic Targeting by 3-Bromopyruvate Saveg Yadav, Shrish Kumar Pandey, Yugal Goel, Mithlesh Kumar Temre, Sukh Mahendra Singh Frontiers in Pharmacology.2019;[Epub] CrossRef
Therapeutic effects of statins against lung adenocarcinoma via p53 mutant-mediated apoptosis Cheng-Wei Chou, Ching-Heng Lin, Tzu-Hung Hsiao, Chia-Chien Lo, Chih-Ying Hsieh, Cheng-Chung Huang, Yuh-Pyng Sher Scientific Reports.2019;[Epub] CrossRef
Drug Repurposing of Metabolic Agents in Malignant Glioma Corinna Seliger, Peter Hau International Journal of Molecular Sciences.2018; 19(9): 2768. CrossRef
The Effect of Statin Added to Systemic Anticancer Therapy: A Meta-Analysis of Randomized, Controlled Trials Hyun Joo Jang, Hyeong Su Kim, Jung Han Kim, Jin Lee Journal of Clinical Medicine.2018; 7(10): 325. CrossRef
Statin therapy in the treatment of active cancer: A systematic review and meta-analysis of randomized controlled trials Mohammed A. M. Farooqi, Nikita Malhotra, Som D. Mukherjee, Stephanie Sanger, Sukhbinder K. Dhesy-Thind, Peter Ellis, Darryl P. Leong, Robert M. Lafrenie PLOS ONE.2018; 13(12): e0209486. CrossRef
Synergistic effect of receptor-interacting protein 140 and simvastatin on the inhibition of proliferation and survival of hepatocellular carcinoma cells Kun Xia, Panpan Zhang, Jian Hu, Huan Hou, Mingdi Xiong, Junping Xiong, Nianlong Yan Oncology Letters.2018;[Epub] CrossRef
Purpose
Concurrent chemoradiotherapy (CCRT) is the standard care for stage III non-small cell lung cancer (NSCLC) patients; however, a more effective regimen is needed to improve the outcome by better controlling occult metastases. We conducted two parallel randomized phase II studies to incorporate erlotinib or irinotecan-cisplatin (IP) into CCRT for stage III NSCLC depending on epidermal growth factor receptor (EGFR) mutation status.
Materials and Methods
Patients with EGFR-mutant tumors were randomized to receive three cycles of erlotinib first and then either CCRT with erlotinib followed by erlotinib (arm A) or CCRT with IP only (arm B). Patients with EGFR unknown or wild-type tumors were randomized to receive either three cycles of IP before (arm C) or after CCRT with IP (arm D).
Results
Seventy-three patients were screened and the study was closed early because of slow accrual after 59 patients were randomized. Overall, there were seven patients in arm A, five in arm B, 22 in arm C, and 25 in arm D. The response rate was 71.4% and 80.0% for arm A and B, and 70.0% and 73.9% for arm C and D. The median overall survival (OS) was 39.3 months versus 31.2 months for arm A and B (p=0.442), and 16.3 months versus 25.3 months for arm C and D (p=0.050). Patients with sensitive EGFR mutations had significantly longer OS than EGFR-wild patients (74.8 months vs. 25.3 months, p=0.034). There were no unexpected toxicities.
Conclusion
Combined-modality treatment by molecular diagnostics is feasible in stage III NSCLC. EGFR-mutant patients appear to be a distinct subset with longer survival.
Citations
Citations to this article as recorded by
Targeted treatment for unresectable EGFR mutation-positive stage III non-small cell lung cancer: Emerging evidence and future perspectives Terufumi Kato, Ignacio Casarini, Manuel Cobo, Corinne Faivre-Finn, Fiona Hegi-Johnson, Shun Lu, Mustafa Özgüroğlu, Suresh S. Ramalingam Lung Cancer.2024; 187: 107414. CrossRef
The ASCENT Trial: a phase 2 study of induction and consolidation afatinib and chemoradiation with or without surgery in stage III EGFR-mutant NSCLC Allison E B Chang, Andrew J Piper-Vallillo, Raymond H Mak, Michael Lanuti, Alona Muzikansky, Julia Rotow, Pasi A Jänne, Mari Mino-Kenudson, Scott Swanson, Cameron D Wright, David Kozono, Paul Marcoux, Zofia Piotrowska, Lecia V Sequist, Henning Willers The Oncologist.2024; 29(7): 609. CrossRef
Management of Non-Metastatic Non-Small Cell Lung Cancer (NSCLC) with Driver Gene Alterations: An Evolving Scenario Valeria Fuorivia, Ilaria Attili, Carla Corvaja, Riccardo Asnaghi, Ambra Carnevale Schianca, Pamela Trillo Aliaga, Ester Del Signore, Gianluca Spitaleri, Antonio Passaro, Filippo de Marinis Current Oncology.2024; 31(9): 5121. CrossRef
Comparison of treatment regimens for unresectable stage III epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer Xin Dai, Qian Xu, Lei Sheng, Xue Zhang, Miao Huang, Song Li, Kai Huang, Jiahui Chu, Jian Wang, Jisheng Li, Yanguo Liu, Jianyuan Zhou, Shulun Nie, Lian Liu Chinese Medical Journal.2024;[Epub] CrossRef
Management of Oncogene Driven Locally Advanced Unresectable Non-small Cell Lung Cancer Jerold Loh, Jia Li Low, Manavi Sachdeva, Peter QJ Low, Rachel Su Jen Wong, Yiqing Huang, Puey Ling Chia, Ross A Soo Expert Review of Anticancer Therapy.2023; 23(9): 913. CrossRef
Peptide-Hydrogel Nanocomposites for Anti-Cancer Drug Delivery Farid Hajareh Haghighi, Roya Binaymotlagh, Ilaria Fratoddi, Laura Chronopoulou, Cleofe Palocci Gels.2023; 9(12): 953. CrossRef
Nuclear accumulation of KPNA2 impacts radioresistance through positive regulation of the PLSCR1‐STAT1 loop in lung adenocarcinoma Wei‐Chao Liao, Tsung‐Jen Lin, Yu‐Chin Liu, Yu‐Shan Wei, Guan‐Ying Chen, Hsiang‐Pu Feng, Yi‐Feng Chang, Hsin‐Tzu Chang, Chih‐Liang Wang, Hsinag‐Cheng Chi, Chun‐I Wang, Kwang‐Huei Lin, Wei‐Ting Ou Yang, Chia‐Jung Yu Cancer Science.2022; 113(1): 205. CrossRef
Erlotinib Versus Etoposide/Cisplatin With Radiation Therapy in Unresectable Stage III Epidermal Growth Factor Receptor Mutation-Positive Non-Small Cell Lung Cancer: A Multicenter, Randomized, Open-Label, Phase 2 Trial Ligang Xing, Gang Wu, Luhua Wang, Jiancheng Li, Jianhua Wang, Zhiyong Yuan, Ming Chen, Yaping Xu, Xiaolong Fu, Zhengfei Zhu, You Lu, Chun Han, Tingyi Xia, Conghua Xie, Guang Li, Shenglin Ma, Bing Lu, Qin Lin, Guangying Zhu, Baolin Qu, Wanqi Zhu, Jinming Y International Journal of Radiation Oncology*Biology*Physics.2021; 109(5): 1349. CrossRef
A systematic review and meta-analysis of treatment-related toxicities of curative and palliative radiation therapy in non-small cell lung cancer M. Or, B. Liu, J. Lam, S. Vinod, W. Xuan, R. Yeghiaian-Alvandi, E. Hau Scientific Reports.2021;[Epub] CrossRef
Tyrosine Kinase Inhibitor Therapy in Unresectable Locally Advanced NSCLC: Keep Holding Our Breaths or Time to Take a Breather? Aruz Mesci, Theodoros Tsakiridis, Anand Swaminath Journal of Thoracic Oncology.2021; 16(10): 1607. CrossRef
Experiences of patients with lung cancer receiving concurrent chemo-radiotherapy Choi Eunsook, Park Sunhee Clinical Journal of Nursing Care and Practice.2021; 5(1): 015. CrossRef
Recent advances and new insights in the management of early-stage epidermal growth factor receptor-mutated non-small-cell lung cancer Miguel J Sotelo, José Luis García, Cesar Torres-Mattos, Héctor Milián, Carlos Carracedo, María Ángeles González-Ruiz, Xabier Mielgo-Rubio, Juan Carlos Trujillo-Reyes, Felipe Couñago World Journal of Clinical Oncology.2021; 12(10): 912. CrossRef
PLGA nanoparticle-reinforced supramolecular peptide hydrogels for local delivery of multiple drugs with enhanced synergism Can Wu, Chunlu Wang, Lu Sun, Keming Xu, Wenying Zhong Soft Matter.2020; 16(46): 10528. CrossRef
Epidermal growth factor receptor tyrosine kinase inhibitors combined with thoracic radiotherapy or chemoradiotherapy for advanced or metastatic non-small cell lung cancer: A systematic review and meta-analysis of single-arm trials Ruifeng Liu, Shihong Wei, Qiuning Zhang, Xueliang Zhang, Hongtao Luo, Jinhui Tian, Yi Li, Long Ge, Xiaohu Wang Medicine.2019; 98(29): e16427. CrossRef
Role of Anti-EGFR Targeted Therapies in Stage III Locally Advanced Non-small Cell Lung Cancer: Give or Not to Give? Sanjal Desai, Chul Kim, Irina Veytsman Current Oncology Reports.2019;[Epub] CrossRef
Pazopanib is a potent multitargeted tyrosine kinase inhibitor that has been shown to have good efficacy in patients with renal cell carcinoma. A previous phase II trial demonstrated that short-term pazopanib administration was generally well tolerated and showed antitumor activity in patients with early-stage non-small cell lung cancer. Herein, we report on the case of a 66-year-old man with simultaneous metastatic squamous cell carcinoma of the lung and renal cell carcinoma who was treated with pazopanib. The patient showed an unexpected partial response and experienced a 10-month progression-free survival without significant toxicity. To the best of the authors’ knowledge, this is the first report of pazopanib treatment in a non-small cell lung cancer patient in Korea. The results in this patient suggest that pazopanib may be a valid treatment option for advanced non-small cell lung cancer.
Since the first description of non-small cell lung cancer (NSCLC) with activating epidermal growth factor receptor (EGFR) mutation as a distinct clinical entity, studies have proved EGFR tyrosine kinase inhibitors (TKIs) as a first choice of treatment. The median response duration of TKIs as a first-line treatment for EGFR mutant tumors ranges from 11 to 14 months. However, acquired resistance to EGFR-TKIs is inevitable due to various mechanisms, such as T790M, c-Met amplification, activation of alternative pathways (IGF-1, HGF, PI3CA, AXL), transformation to mesenchymal cell or small cell features, and tumor heterogeneity. Until development of a successful treatment strategy to overcome such acquired resistance, few options are currently available. Here we provide a summary of the therapeutic options after failure of first line EGFR-TKI treatment for NSCLC.
Citations
Citations to this article as recorded by
The clinicopathologic of pulmonary adenocarcinoma transformation to small cell lung cancer Haiyan Yang, Li Liu, Chunhua Zhou, Yi Xiong, Yijuan Hu, Nong Yang, Jingjing Qu Medicine.2019; 98(12): e14893. CrossRef
Histological transformation of adenocarcinoma to small cell carcinoma lung as a rare mechanism of resistance to epidermal growth factor receptor-tyrosine kinase inhibitors: Report of a case with review of literature Monalisa Hui, ShantveerG Uppin, BalaJoseph Stalin, G Sadashivudu Lung India.2018; 35(2): 160. CrossRef
Predictive Factors for Switched EGFR-TKI Retreatment in Patients with EGFR-Mutant Non-Small Cell Lung Cancer Byoung Soo Kwon, Ji Hyun Park, Woo Sung Kim, Joon Seon Song, Chang-Min Choi, Jin Kyung Rho, Jae Cheol Lee Tuberculosis and Respiratory Diseases.2017; 80(2): 187. CrossRef
Acquired Resistance to Erlotinib in EGFR Mutation-Positive Lung Adenocarcinoma among Hispanics (CLICaP) Andrés F. Cardona, Oscar Arrieta, Martín Ignacio Zapata, Leonardo Rojas, Beatriz Wills, Noemí Reguart, Niki Karachaliou, Hernán Carranza, Carlos Vargas, Jorge Otero, Pilar Archila, Claudio Martín, Luis Corrales, Mauricio Cuello, Carlos Ortiz, Luis E. Pino Targeted Oncology.2017; 12(4): 513. CrossRef
Integrating Models to Quantify Environment-Mediated Drug Resistance Noemi Picco, Erik Sahai, Philip K. Maini, Alexander R.A. Anderson Cancer Research.2017; 77(19): 5409. CrossRef
Histological transformation from non‐small cell to small cell lung carcinoma after treatment with epidermal growth factor receptor‐tyrosine kinase inhibitor Woo‐Jin Kim, Sunmin Kim, Hayoung Choi, Jinsun Chang, Hong‐Joon Shin, Cheol‐Kyu Park, In‐Jae Oh, Kyu‐Sik Kim, Young‐Chul Kim, Yoo‐Duk Choi Thoracic Cancer.2015; 6(6): 800. CrossRef
Clinically beneficial continued treatment with gefitinib after asymptomatic progression of lung adenocarcinoma Hayoung Choi, Jinsun Chang, Hong‐Joon Shin, Cheol‐Kyu Park, In‐Jae Oh, Kyu‐Sik Kim, Young‐Chul Kim Thoracic Cancer.2015; 6(2): 224. CrossRef
The Continuation of Erlotinib Treatment in Non-Small Cell Lung Cancer Patients Whose Brain Lesion Is the Only Site of Progression: Prospective Pilot Study Kwai Han Yoo, Seung Tae Kim, Ki Sun Jung, Ji Yun Lee, Sung Hee Lim, Min-Young Lee, Hae Soo Kim, Hee Jin Kwon, In Young Kim, Jong-Mu Sun, Jin Seok Ahn, Keunchil Park, Myung-Ju Ahn Hanyang Medical Reviews.2015; 35(3): 180. CrossRef
Peptide Nucleic Acid Clamping Versus Direct Sequencing for the Detection of EGFR Gene Mutation in Patients with Non-small Cell Lung Cancer Seong-Hoon Yoon, Yoo-Duk Choi, In-Jae Oh, Kyu-Sik Kim, Hayoung Choi, Jinsun Chang, Hong-Joon Shin, Cheol-Kyu Park, Young-Chul Kim Cancer Research and Treatment.2015; 47(4): 661. CrossRef
Long Term Therapeutic Plan for Patients with Non-Small Cell Lung Cancer HarboringEGFRMutation Seung Hun Jang Tuberculosis and Respiratory Diseases.2014; 76(1): 8. CrossRef
Multiplexed immunohistochemistry, imaging, and quantitation: A review, with an assessment of Tyramide signal amplification, multispectral imaging and multiplex analysis Edward C. Stack, Chichung Wang, Kristin A. Roman, Clifford C. Hoyt Methods.2014; 70(1): 46. CrossRef
Comparison of pemetrexed and docetaxel as salvage chemotherapy for the treatment for nonsmall-cell lung cancer after the failure of epidermal growth factor receptor-tyrosine kinase inhibitors Lei Dong, Zhao-feng Han, Zi-hui Feng, Zhi-yang Jia Journal of International Medical Research.2014; 42(1): 191. CrossRef
Heterogeneity of epidermal growth factor receptor mutations in lung adenocarcinoma harboring anaplastic lymphoma kinase rearrangements: A case report QIONG SUN, JIAN-YU WU, SHUN-CHANG JIAO Oncology Letters.2014; 8(5): 2093. CrossRef
Post-Progression Survival in Patients with Non-Small Cell Lung Cancer with Clinically Acquired Resistance to Gefitinib Hyojeong Kim, Tak Yun, Young Joo Lee, Ji-Youn Han, Heung Tae Kim, Geon Kook Lee Journal of Korean Medical Science.2013; 28(11): 1595. CrossRef
Locally advanced non-small cell lung cancer (NSCLC) is a heterogeneous disease, and we have embarked on an era where patients will benefit from individualized therapeutic strategies based on identifiable molecular characteristics of the tumor. The landmark studies demonstrating the importance of molecular characterization of tumors for NSCLC patients, the promising molecular pathways, and the potential molecular targets/agents for treatment of this disease will be reviewed. Understanding these issues will aid in the development of rationally designed clinical trials, so as to determine best means of appropriately incorporating these molecular strategies, to the current standard of radiation and chemotherapy regimens, for the treatment of locally advanced NSCLC.
Citations
Citations to this article as recorded by
The Correlation between Hemostatic Parameters and Mortality Rate in Patients with Non-Small Cell Lung Cancer Noni Novisari Soeroso, Fannie Rizki Ananda, Ganda Samosir, Herman Hariman, Putri Chairani Eyanoer Hematology Reports.2021; 13(3): 8361. CrossRef
Radiation Therapy as a Backbone of Treatment of Locally Advanced Non-Small Cell Lung Cancer Aaron M. Laine, Kenneth D. Westover, Hak Choy Seminars in Oncology.2014; 41(1): 57. CrossRef
Recurrence and Survival Outcomes After Anatomic Segmentectomy Versus Lobectomy for Clinical Stage I Non–Small-Cell Lung Cancer: A Propensity-Matched Analysis Rodney J. Landreneau, Daniel P. Normolle, Neil A. Christie, Omar Awais, Joseph J. Wizorek, Ghulam Abbas, Arjun Pennathur, Manisha Shende, Benny Weksler, James D. Luketich, Matthew J. Schuchert Journal of Clinical Oncology.2014; 32(23): 2449. CrossRef
High concordance of EGFR mutation status between histologic and corresponding cytologic specimens of lung adenocarcinomas Ping‐Li Sun, Yan Jin, Hyojin Kim, Choon‐Taek Lee, Sanghoon Jheon, Jin‐Haeng Chung Cancer Cytopathology.2013; 121(6): 311. CrossRef
Thrombocytosis and immunohistochemical expression of connexin 43 at diagnosis predict survival in advanced non-small-cell lung cancer treated with cisplatin-based chemotherapy Gangjun Du, Yingming Yang, Yaping Zhang, Ting Sun, Weijie Liu, Yingying Wang, Jiahuan Li, Houyun Zhang Cancer Chemotherapy and Pharmacology.2013; 71(4): 893. CrossRef
Coombs' negative autoimmune hemolytic anemia (AIHA) is a rare disease which shares similar clinical and hematological features with Coombs' positive AIHA, but its exact frequency remains unknown. There have been few reports of idiopathic thrombocytopenic purpura (ITP) and Coombs' negative AIHA associated with other lymphoproliferative disorders (LPDs).
Since there is a well known association between LPDs and autoimmune phenomena, it is important to investigate the possibility of an underlying malignancy. We report a case of ITP and Coombs' negative AIHA associated with diffuse large B-cell lymphoma.
Citations
Citations to this article as recorded by
Treatment of Secondary Immune Thrombocytopenia with Non-Hodgkin Lymphoma: A Case Report and Literature Review Yuya Kurihara, Kazuki Taoka, Eri Takagi, Kazuhiro Toyama, Kumi Nakazaki, Mineo Kurokawa Internal Medicine.2021; 60(10): 1583. CrossRef
Primary, secondary or less frequent causes of immune thrombocytopenia: A case report Minodora Onisâi, Ana-Maria Vlădăreanu, Iuliana Iordan, Horia Bumbea, Mihaela Găman, Cristina Ciufu, Irina Voican, Diana Cîșleanu, Daniela Vasile, Cristina Marinescu, Anca Nicolescu, Andreea Spînu, Raluca Nistor, Adrian Alexandru Experimental and Therapeutic Medicine.2021;[Epub] CrossRef
Efficacy of bendamustine on thrombocytopenia and hemolytic anemia secondary to CD5-positive B-cell lymphoma with massive splenomegaly in a patient with rheumatoid arthritis Yuzuru Hosoda, Hiroshi Hagino, Norihiko Hino, Toru Motokura Molecular and Clinical Oncology.2017; 7(5): 855. CrossRef
Synchronous Occurrence of Diffuse Large B-cell Lymphoma of the Duodenum and Gastrointestinal Stromal Tumor of the Ileum in a Patient with Immune Thrombocytopenic Purpura Tohru Takahashi, Yumiko Maruyama, Mayuko Saitoh, Hideto Itoh, Mitsuru Yoshimoto, Masayuki Tsujisaki, Masato Nakayama Internal Medicine.2016; 55(20): 2951. CrossRef
Clinical and reference lab characteristics of patients with suspected direct antiglobulin test (DAT)-negative immune hemolytic anemia M.S. Karafin, G.A. Denomme, M. Schanen, J.L. Gottschall Immunohematology.2015; 31(3): 108. CrossRef