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Original Articles
Gastrointestinal cancer
Efficacy of Lenvatinib Combined with Anti–PD-1 Antibodies Plus Transcatheter Arterial Chemoembolization for Hepatocellular Carcinoma with Portal Vein Tumor Thrombus: A Retrospective, Multicenter Study
Xiangye Ou, Junyi Wu, Jiayi Wu, Yangkai Fu, Zhenxin Zeng, Shuqun Li, Yinan Li, Deyi Liu, Han Li, Bin Li, Jianyin Zhou, Shaowu Zhuang, Shuqun Cheng, Zhibo Zhang, Kai Wang, Shuang Qu, Maolin Yan
Cancer Res Treat. 2024;56(4):1207-1218.   Published online April 30, 2024
DOI: https://doi.org/10.4143/crt.2023.1165
AbstractAbstract PDFSupplementary MaterialPubReaderePub
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.
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Head and Neck cancer
Analysis of Response and Progression Patterns of Tyrosine Kinase Inhibitors in Recurrent or Metastatic Adenoid Cystic Carcinoma: A Post Hoc Analysis of Two KCSG Phase II Trials
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
DOI: https://doi.org/10.4143/crt.2024.008
AbstractAbstract PDFSupplementary MaterialPubReaderePub
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.
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Lung and Thoracic cancer
Targeting CD73 to Overcomes Resistance to First-Generation EGFR Tyrosine Kinase Inhibitors in Non–Small Cell Lung Cancer
Miso Kim, Soyeon Kim, Jeemin Yim, Bhumsuk Keam, Tae Min Kim, Yoon Kyung Jeon, Dong-Wan Kim, Dae Seog Heo
Cancer Res Treat. 2023;55(4):1134-1143.   Published online May 23, 2023
DOI: https://doi.org/10.4143/crt.2023.311
AbstractAbstract PDFSupplementary MaterialPubReaderePub
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
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EGFR-TKI Combined with Pemetrexed versus EGFR-TKI Monotherapy in Advanced EGFR-Mutated NSCLC: A Prospective, Randomized, Exploratory Study
Weiguang Gu, Hua Zhang, Yiyu Lu, Minjing Li, Shuang Yang, Jianmiao Liang, Zhijian Ye, Zhihua Li, Minhong He, Xiaoliang Shi, Fei Wang, Dong You, Weiquan Gu, Weineng Feng
Cancer Res Treat. 2023;55(3):841-850.   Published online February 13, 2023
DOI: https://doi.org/10.4143/crt.2022.1438
AbstractAbstract PDFSupplementary MaterialPubReaderePub
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
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Hematologic malignancy
Clinical Impact of Drug Adherence of Tyrosine Kinase Inhibitors in Children with Ph-Positive Acute Lymphoblastic Leukemia
Jun-Xia Wang, Miao-Miao Yang, Li-Peng Liu, Hui-Min Zhang, Meng-Chuan Wang, Yu-Wen Chen, Xiao-Ying Zang, Fang Hu
Cancer Res Treat. 2023;55(3):1023-1030.   Published online February 6, 2023
DOI: https://doi.org/10.4143/crt.2022.1618
AbstractAbstract PDFPubReaderePub
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.
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Lung and Thoracic cancer
The Clinical Outcomes of Different First-Line EGFR-TKIs Plus Bevacizumab in Advanced EGFR-Mutant Lung Adenocarcinoma
Yen-Hsiang Huang, Kuo-Hsuan Hsu, Chun-Shih Chin, Jeng-Sen Tseng, Tsung-Ying Yang, Kun-Chieh Chen, Kang-Yi Su, Sung-Liang Yu, Jeremy J.W. Chen, Gee-Chen Chang
Cancer Res Treat. 2022;54(2):434-444.   Published online August 2, 2021
DOI: https://doi.org/10.4143/crt.2021.671
AbstractAbstract PDFPubReaderePub
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
  • Afatinib/bevacizumab/erlotinib

    Reactions Weekly.2023; 1952(1): 32.     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
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Case Report
EGFR C797S as a Resistance Mechanism of Lazertinib in Non-small Cell Lung Cancer with EGFR T790M Mutation
Sehhoon Park, Bo Mi Ku, Hyun Ae Jung, Jong-Mu Sun, Jin Seok Ahn, Se-Hoon Lee, Keunchil Park, Myung-Ju Ahn
Cancer Res Treat. 2020;52(4):1288-1290.   Published online June 22, 2020
DOI: https://doi.org/10.4143/crt.2020.278
AbstractAbstract PDFPubReaderePub
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
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    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
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    Kyu Sic You, Yong Weon Yi, Jeonghee Cho, Jeong-Soo Park, Yeon-Sun Seong
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    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
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Original Articles
Breast cancer
Real-World Data of Pyrotinib-Based Therapy in Metastatic HER2-Positive Breast Cancer: Promising Efficacy in Lapatinib-Treated Patients and in Brain Metastasis
Ying Lin, Mingxi Lin, Jian Zhang, Biyun Wang, Zhonghua Tao, Yiqun Du, Sheng Zhang, Jun Cao, Leiping Wang, Xichun Hu
Cancer Res Treat. 2020;52(4):1059-1066.   Published online April 24, 2020
DOI: https://doi.org/10.4143/crt.2019.633
AbstractAbstract PDFSupplementary MaterialPubReaderePub
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
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    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
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    Yueyue Liu, Qian Zhang, Chao Lu, Wei Hu
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RON and MET Co-overexpression Are Significant Pathological Characteristics of Poor Survival and Therapeutic Targets of Tyrosine Kinase Inhibitors in Triple-Negative Breast Cancer
Tian-Hao Weng, Min-Ya Yao, Xiang-Ming Xu, Chen-Yu Hu, Shu-Hao Yao, Yi-Zhi Liu, Zhi-Gang Wu, Tao-Ming Tang, Pei-Fen Fu, Ming-Hai Wang, Hang-Ping Yao
Cancer Res Treat. 2020;52(3):973-986.   Published online April 22, 2020
DOI: https://doi.org/10.4143/crt.2019.726
AbstractAbstract PDFSupplementary MaterialPubReaderePub
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.

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  • 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
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    Alex Cazes, Betzaira G. Childers, Edgar Esparza, Andrew M. Lowy
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  • 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
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Osimertinib in Patients with T790M-Positive Advanced Non-small Cell Lung Cancer: Korean Subgroup Analysis from Phase II Studies
Myung-Ju Ahn, Ji-Youn Han, Dong-Wan Kim, Byoung Chul Cho, Jin-Hyoung Kang, Sang-We Kim, James Chih-Hsin Yang, Tetsuya Mitsudomi, Jong Seok Lee
Cancer Res Treat. 2020;52(1):284-291.   Published online July 23, 2019
DOI: https://doi.org/10.4143/crt.2019.200
AbstractAbstract PDFPubReaderePub
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.

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Acquired Resistance of MET-Amplified Non-small Cell Lung Cancer Cells to the MET Inhibitor Capmatinib
Seulki Kim, Tae Min Kim, Dong-Wan Kim, Soyeon Kim, Miso Kim, Yong-Oon Ahn, Bhumsuk Keam, Dae Seog Heo
Cancer Res Treat. 2019;51(3):951-962.   Published online October 10, 2018
DOI: https://doi.org/10.4143/crt.2018.052
AbstractAbstract PDFSupplementary MaterialPubReaderePub
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.

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Clinical Outcomes of EGFR Exon 20 Insertion Mutations in Advanced Non-small Cell Lung Cancer in Korea
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
DOI: https://doi.org/10.4143/crt.2018.151
AbstractAbstract PDFSupplementary MaterialPubReaderePub
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.

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Impact of Pulmonary Tuberculosis on the EGFR Mutational Status and Clinical Outcome in Patients with Lung Adenocarcinoma
In Kyoung Hwang, Seung Sook Paik, Seung Hyeun Lee
Cancer Res Treat. 2019;51(1):158-168.   Published online April 2, 2018
DOI: https://doi.org/10.4143/crt.2018.084
AbstractAbstract PDFSupplementary MaterialPubReaderePub
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.

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EGFR Mutation Status in Lung Adenocarcinoma-Associated Malignant Pleural Effusion and Efficacy of EGFR Tyrosine Kinase Inhibitors
Jiyoul Yang, Ok-Jun Lee, Seung-Myoung Son, Chang Gok Woo, Yusook Jeong, Yaewon Yang, Jihyun Kwon, Ki Hyeong Lee, Hye Sook Han
Cancer Res Treat. 2018;50(3):908-916.   Published online September 19, 2017
DOI: https://doi.org/10.4143/crt.2017.378
AbstractAbstract PDFPubReaderePub
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.

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Incorporating Neutrophil-to-lymphocyte Ratio and Platelet-to-lymphocyte Ratio in Place of Neutrophil Count and Platelet Count Improves Prognostic Accuracy of the International Metastatic Renal Cell Carcinoma Database Consortium Model
Pawel Chrom, Rafal Stec, Lubomir Bodnar, Cezary Szczylik
Cancer Res Treat. 2018;50(1):103-110.   Published online March 3, 2017
DOI: https://doi.org/10.4143/crt.2017.033
AbstractAbstract PDFSupplementary MaterialPubReaderePub
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.

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Randomized Phase II Study of Afatinib Plus Simvastatin Versus Afatinib Alone in Previously Treated Patients with Advanced Nonadenocarcinomatous Non-small Cell Lung Cancer
Youngjoo Lee, Ki Hyeong Lee, Geon Kook Lee, Soo-Hyun Lee, Kun Young Lim, Jungnam Joo, Yun Jung Go, Jin Soo Lee, Ji-Youn Han
Cancer Res Treat. 2017;49(4):1001-1011.   Published online January 13, 2017
DOI: https://doi.org/10.4143/crt.2016.546
AbstractAbstract PDFPubReaderePub
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.

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    Sabine Galland, Patricia Martin, Giulia Fregni, Igor Letovanec, Ivan Stamenkovic
    Cancer Letters.2020; 484: 50.     CrossRef
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    John P. Thomas, Yoon K. Loke, Leo Alexandre
    European Journal of Clinical Pharmacology.2020; 76(12): 1639.     CrossRef
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    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
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    Joseph C. Murray, Benjamin Levy
    The Cancer Journal.2019; 25(2): 127.     CrossRef
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    Frontiers in Pharmacology.2019;[Epub]     CrossRef
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Incorporating Erlotinib or Irinotecan Plus Cisplatin into Chemoradiotherapy for Stage III Non-small Cell Lung Cancer According to EGFR Mutation Status
Youngjoo Lee, Ji-Youn Han, Sung Ho Moon, Byung-Ho Nam, Kun Young Lim, Geon Kook Lee, Heung Tae Kim, Tak Yun, Hye Jin An, Jin Soo Lee
Cancer Res Treat. 2017;49(4):981-989.   Published online January 6, 2017
DOI: https://doi.org/10.4143/crt.2016.522
AbstractAbstract PDFSupplementary MaterialPubReaderePub
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

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    Terufumi Kato, Ignacio Casarini, Manuel Cobo, Corinne Faivre-Finn, Fiona Hegi-Johnson, Shun Lu, Mustafa Özgüroğlu, Suresh S. Ramalingam
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Case Report
Pazopanib for Non-small Cell Lung Cancer: The First Case Report in Korea
Jaemin Jo, Jung Ho Kim, Ji Young Kim, Changlim Hyun, Jiyoung Rhee, Jungmi Kwon, Sanghoon Han, Wookun Kim
Cancer Res Treat. 2016;48(1):393-397.   Published online February 17, 2015
DOI: https://doi.org/10.4143/crt.2014.209
AbstractAbstract PDFPubReaderePub
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.
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Review Articles
Treatment of Non-small Cell Lung Carcinoma after Failure of Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor
Jae Cheol Lee, Seung Hun Jang, Kye Young Lee, Young-Chul Kim
Cancer Res Treat. 2013;45(2):79-85.   Published online June 30, 2013
DOI: https://doi.org/10.4143/crt.2013.45.2.79
AbstractAbstract PDFPubReaderePub
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.

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Personalized Combined Modality Therapy for Locally Advanced Non-small Cell Lung Cancer
D. Nathan Kim, Taek-Keun Nam, Kevin S. Choe, Hak Choy
Cancer Res Treat. 2012;44(2):74-84.   Published online June 30, 2012
DOI: https://doi.org/10.4143/crt.2012.44.2.74
AbstractAbstract PDFPubReaderePub
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.

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  • 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
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    Aaron M. Laine, Kenneth D. Westover, Hak Choy
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    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
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  • 71 Download
  • 5 Crossref
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Editorial
New Step of Joint Publication with the Korean Association for Clinical Oncology
Il Han Kim
Cancer Res Treat. 2012;44(2):73-73.   Published online June 30, 2012
DOI: https://doi.org/10.4143/crt.2012.44.2.73
AbstractAbstract PDFPubReaderePub
No abstract available.
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Case Report
A Case of Non-Hodgkin's Lymphoma in Patient with Coombs' Negative Hemolytic Anemia and Idiopathic Thrombocytopenic Purpura
So Yeon Park, Soyon Kim, Eun Sil Kim, Soon Uk Choi, Hee Jae Hyun, Ju Young Ahn, Ju Hyoung Lee, Seo Hee Ryu, Jae Hyun Park, Gyeong In Lee, Hyo Jin Lee
Cancer Res Treat. 2012;44(1):69-72.   Published online March 31, 2012
DOI: https://doi.org/10.4143/crt.2012.44.1.69
AbstractAbstract PDFPubReaderePub
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.

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