Purpose Capmatinib, an oral MET kinase inhibitor, has demonstrated its efficacy against non–small cell lung cancer (NSCLC) with MET dysregulation. We investigated its clinical impact in advanced NSCLC with MET exon 14 skipping mutation (METex14) or gene amplification.
Materials and Methods Patients who participated in the screening of a phase II study of capmatinib for advanced NSCLC were enrolled in this study. MET gene copy number (GCN), protein expression, and METex14 were analyzed and the patients’ clinical outcome were retrospectively reviewed.
Results A total of 72 patients were included in this analysis (group A: GCN ≥ 10 or METex14, n=14; group B: others, n=58). Among them, 13 patients were treated with capmatinib (group A, n=8; group B, n=5), and the overall response rate was 50% for group A, and 0% for group B. In all patients, the median overall survival (OS) was 20.2 months (95% confidence interval [CI], 6.9 to not applicable [NA]) for group A, and 11.3 months (95% CI, 8.2 to 20.3) for group B (p=0.457). However, within group A, median OS was 21.5 months (95% CI, 20.8 to NA) for capmatinib-treated, and 7.5 months (95% CI, 3.2 to NA) for capmatinib-untreated patients (p=0.025). Among all capmatinib-untreated patients (n=59), group A showed a trend towards worse OS to group B (median OS, 7.5 months vs. 11.3 months; p=0.123).
Conclusion Our data suggest that capmatinib is a new compelling treatment for NSCLC with MET GCN ≥ 10 or METex14 based on the improved survival within these patients.
Citations
Citations to this article as recorded by
Exploring Cellular Plasticity and Resistance Mechanisms in Lung Cancer: Innovations and Emerging Therapies Caiyu Jiang, Shenglong Xie, Kegang Jia, Gang Feng, Xudong Ren, Youyu Wang Journal of Pharmaceutical Analysis.2025; : 101179. CrossRef
EGFR and PI3K Signalling Pathways as Promising Targets on Circulating Tumour Cells from Patients with Metastatic Gastric Adenocarcinoma Ann-Katrin Piper, Chelsea Penney, Jacqueline Holliday, Gary Tincknell, Yafeng Ma, Sarbar Napaki, Klaus Pantel, Daniel Brungs, Marie Ranson International Journal of Molecular Sciences.2024; 25(10): 5565. CrossRef
Understanding the treatment response and resistance to targeted therapies in non-small cell lung cancer: clinical insights and perspectives Hang Zhang, Yingying Zhang, Yingying Zhu, Tian Dong, Zheng Liu Frontiers in Oncology.2024;[Epub] CrossRef
Synthesis and bioassay of 3-Aryl -1-(pyridin-4-yl)benzo[4,5]imidazo[1,2-d][1,2,4]- triazin-4(3H)-ones as anti-cancer agents Bassam Abu Thaher, Ihab Al-Masri, Kanan Wahedy, Rami Morjan, Saeb Aliwaini, Iman Mahmoud Al atter, Aayat Ahmed Elmabhouh, Areej khaled AL ibwaini, Saba Luay Alkhaldi, Basem Qeshta, Claus Jacob, Hans-Peter Deigner Naunyn-Schmiedeberg's Archives of Pharmacology.2023; 396(8): 1797. CrossRef
RNA splicing alterations in lung cancer pathogenesis and therapy Yueren Yan, Yunpeng Ren, Yufang Bao, Yongbo Wang Cancer Pathogenesis and Therapy.2023; 1(4): 272. CrossRef
Clinicopathological characteristics of Non-Small Cell Lung Cancer (NSCLC) patients with c-MET exon 14 skipping mutation, MET overexpression and amplification Caixia Ding, Yanyi Qiu, Juan Zhang, Wei Wei, Hongbian Gao, Yong Yuan, Xiaomin Wang BMC Pulmonary Medicine.2023;[Epub] CrossRef
Long-Term Efficacy, Safety, and Subgroup Analysis of Savolitinib in Chinese Patients With NSCLCs Harboring MET Exon 14 Skipping Alterations Shun Lu, Jian Fang, Xingya Li, Lejie Cao, Jianying Zhou, Qisen Guo, Zongan Liang, Ying Cheng, Liyan Jiang, Nong Yang, Zhigang Han, Jianhua Shi, Yuan Chen, Hua Xu, Helong Zhang, Gongyan Chen, Rui Ma, Sanyuan Sun, Yun Fan, Songhua Fan, Jie Yu, Puhan Lu, Xia JTO Clinical and Research Reports.2022; 3(10): 100407. CrossRef
HPLC with Fluorescence and Photodiode Array Detection for Quantifying Capmatinib in Biological Samples: Application to In Vivo and In Vitro Studies Aref Zayed, Sana’a A. Jaber, Jomana Al Hroot, Sahar Hawamdeh, Nehad M. Ayoub, Nidal A. Qinna Molecules.2022; 27(23): 8582. CrossRef
Evaluation of MET alteration in EGFR-mutant non-small cell lung cancer patients treated with EGFR tyrosine kinase inhibitor from paired biopsy: A retrospective cohort study Bo Mi Ku, Sungwon Park, Sehhoon Park, Hyun Ae Jung, Jong-Mu Sun, Se-Hoon Lee, Jin Seok Ahn, Yoon-La Choi, Myung-Ju Ahn Precision and Future Medicine.2022; 6(4): 233. CrossRef
Targeted Treatment of Non-Small Cell Lung Cancer: Focus on Capmatinib with Companion Diagnostics Matthew Z Guo, Kristen A Marrone, Alexander Spira, David M Waterhouse, Susan C Scott OncoTargets and Therapy.2021; Volume 14: 5321. CrossRef
Purpose
Squamous cell carcinomas (SqCC) of the lung often express high levels of thymidylate synthase (TS), which is associated with primary resistance to pemetrexed. We explored the efficacy of pemetrexed in a selected population of patients with lung SqCC with low TS expression.
Materials and Methods
In this single-arm phase II trial, we enrolled 32 previously-treated patients with advanced lung SqCC exhibiting low immunohistochemical staining for TS (i.e., in 10% or less of tumor cells). The primary endpoint was 12-week progression-free survival (PFS) rate.
Results
Of 32 patients, eight patients (25%) had an Eastern Cooperative Oncology Group performance status of 2, and seven patients (22%) had previously received three or more lines of chemotherapy. The disease control rate from pemetrexed treatment was 30%, and no objective response was observed. The 12-week PFS rate was 24.5% (95% confidence interval [CI], 13.0 to 46.1). Median PFS was 1.3 months (95% CI, 1.3 to 2.7), and median overall survival was 11.8 months (95% CI, 8.1 to not applicable). Most of adverse events were grade 1 or 2.
Conclusion
Pemetrexed demonstrated modest activity as a salvage chemotherapy in patients with advanced lung SqCC with low TS expression, although its toxicity was generally manageable.
Citations
Citations to this article as recorded by
Bioengineered miR-7-5p modulates non–small cell lung cancer cell metabolism to improve therapy Gavin M. Traber, Mei-Juan Tu, Su Guan, Neelu Batra, Ai-Ming Yu Molecular Pharmacology.2025; 107(1): 100006. CrossRef
Purpose
Because of growing concerns about lung cancer in female never smokers, chest low-dose computed tomography (LDCT) screening is often performed although it has never shown clinical benefits. We examinewhether or not female never smokers really need annual LDCT screening when the initial LDCT showed negative findings.
Materials and Methods
This retrospective cohort study included 4,365 female never smokers aged 40 to 79 years who performed initial LDCT from Aug 2002 to Dec 2007. Lung cancer diagnosis was identified from the Korea Central Cancer Registry Database registered until December 31, 2013. We calculated the incidence, cumulative probability, and standardized incidence ratio (SIR) of lung cancer by Lung Imaging Reporting and Data System (Lung-RADS) categories showed on initial LDCT.
Results
After median follow-up of 9.69 years, 22 (0.5%) had lung cancer. Lung cancer incidence for Lung-RADS category 4 was 1,848.4 (95% confidence interval [CI], 1,132.4 to 3,017.2) per 100,000 person-years and 16.4 (95% CI, 7.4 to 36.4) for categories 1, 2, and 3 combined. The cumulative probability of lung cancer for category 4 was 10.6% at 5 years and 14.8% at 10 years while they were 0.07% and 0.17% when categories 1, 2, and 3 were combined. The SIR for subjects with category 4 was 43.80 (95% CI, 25.03 to 71.14), which was much higher than 0.47 (95% CI, 0.17 to 1.02) for categories 1, 2, and 3 combined.
Conclusion
Considering the low risk of lung cancer development in female never smokers, it seems unnecessary to repeat annual LDCT screening for at least 5 years or even longer unless the initial LDCT showed Lung-RADS category 4 findings.
Citations
Citations to this article as recorded by
Radiological Changes in Chest CT findings of School Cafeteria Workers: A Comparative Study with Age-Matched Controls Jung Hee Hong, Jin Young Kim, Kiook Baek Safety and Health at Work.2025;[Epub] CrossRef
Lung cancer screening for never smokers: current evidence and future directions Kay Choong See Singapore Medical Journal.2024;[Epub] CrossRef
Cooking oil fume exposure and Lung-RADS distribution among school cafeteria workers of South Korea Minjun Kim, Yangho Kim, A Ram Kim, Woon Jung Kwon, Soyeoun Lim, Woojin Kim, Cheolin Yoo Annals of Occupational and Environmental Medicine.2024;[Epub] CrossRef
Distribution of Solid Lung Nodules Presence and Size by Age and Sex in a Northern European Nonsmoking Population Jiali Cai, Marleen Vonder, Gert Jan Pelgrim, Mieneke Rook, Gerdien Kramer, Harry J.M. Groen, Geertruida H. de Bock, Rozemarijn Vliegenthart Radiology.2024;[Epub] CrossRef
Low Dose Computed Tomography for Lung Cancer Screening in Tuberculosis Endemic Countries: A Systematic Review and Meta-Analysis Vikram Damaraju, Juhu Kiran Krushna Karri, Gayathri Gandrakota, Yamini Marimuthu, Adimulam Ganga Ravindra, Rajeev Aravindakshan, Navneet Singh Journal of Thoracic Oncology.2024;[Epub] CrossRef
Toward More Effective Lung Cancer Risk Stratification to Empower Screening Programs for the Asian Nonsmoking Population Fu-Zong Wu, Yeun-Chung Chang Journal of the American College of Radiology.2023; 20(2): 156. CrossRef
ACR Appropriateness Criteria® Lung Cancer Screening: 2022 Update Kim L. Sandler, Travis S. Henry, Arya Amini, Saeed Elojeimy, Aine Marie Kelly, Christopher T. Kuzniewski, Elizabeth Lee, Maria D. Martin, Michael F. Morris, Neeraja B. Peterson, Constantine A. Raptis, Gerard A. Silvestri, Arlene Sirajuddin, Betty C. Tong, Journal of the American College of Radiology.2023; 20(5): S94. CrossRef
Performance of Lung-RADS in different target populations: a systematic review and meta-analysis Yifei Mao, Jiali Cai, Marjolein A. Heuvelmans, Rozemarijn Vliegenthart, Harry J. M. Groen, Matthijs Oudkerk, Marleen Vonder, Monique D. Dorrius, Geertruida H. de Bock European Radiology.2023; 34(3): 1877. CrossRef
Lung cancer screening in never-smokers: facts and remaining issues Maurizio V. Infante, Giuseppe Cardillo European Respiratory Journal.2020; 56(5): 2002949. CrossRef
Low-dose chest computed tomographic screening and invasive diagnosis of pulmonary nodules for lung cancer in never-smokers Yeon Wook Kim, Hye-Rin Kang, Byoung Soo Kwon, Sung Yoon Lim, Yeon Joo Lee, Jong Sun Park, Young-Jae Cho, Ho Il Yoon, Kyung Won Lee, Jae Ho Lee, Choon-Taek Lee European Respiratory Journal.2020; 56(5): 2000177. CrossRef
Predicting Lung Cancer Occurrence in Never-Smoking Females in Asia: TNSF-SQ, a Prediction Model Li-Hsin Chien, Chung-Hsing Chen, Tzu-Yu Chen, Gee-Chen Chang, Ying-Huang Tsai, Chin-Fu Hsiao, Kuan-Yu Chen, Wu-Chou Su, Wen-Chang Wang, Ming-Shyan Huang, Yuh-Min Chen, Chih-Yi Chen, Sheng-Kai Liang, Chung-Yu Chen, Chih-Liang Wang, Mei-Hsuan Lee, Ren-Hua C Cancer Epidemiology, Biomarkers & Prevention.2020; 29(2): 452. CrossRef
Role of Low-Dose Computerized Tomography in Lung Cancer Screening among Never-Smokers Hye-Rin Kang, Jun Yeun Cho, Sang Hoon Lee, Yeon Joo Lee, Jong Sun Park, Young-Jae Cho, Ho Il Yoon, Kyung Won Lee, Jae Ho Lee, Choon-Taek Lee Journal of Thoracic Oncology.2019; 14(3): 436. CrossRef
Prevention and Early Detection for NSCLC: Advances in Thoracic Oncology 2018 Haval Balata, Kwun M. Fong, Lizza E. Hendriks, Stephen Lam, Jamie S. Ostroff, Nir Peled, Ning Wu, Charu Aggarwal Journal of Thoracic Oncology.2019; 14(9): 1513. 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
Purpose
We evaluated the clinical utility of excision repair cross-complementation group 1 (ERCC1) expression as a predictive biomarker for platinum-based chemotherapy in advanced non-small cell lung cancer (NSCLC).
Materials and Methods
Eligible patients were randomly assigned to the GP (gemcitabine 1,250 mg/m2 on days 1 and 8, and cisplatin 75 mg/m2 on day 1 every 3 weeks) or IP (irinotecan 65 mg/m2 and cisplatin 30 mg/m2 on days 1 and 8 every 3 weeks) arm. The primary goal of this study was to compare the response rate (RR) of the GP and IP arms according to the ERCC1 expression level.
Results
A total of 279 patients were randomly assigned to the GP (n=139) and IP (n=140) arms, among which 63% were ERCC1-positive and 268 patients were assessable for the RR. The GP and IP arms did not differ significantly with respect to the RR (29.8% vs. 27.0%, respectively; p=0.082), median progression-free survival (PFS; 4.5 months vs. 3.9 months, respectively; p=0.117), and overall survival (OS; 16.5 months vs. 16.7 months, respectively; p=0.313). When comparing the efficacy between the ERCC1-positive and ERCC1-negative groups, there was no significant difference in the RR (GP, 28.2% vs. 32.6%, respectively, p=0.509; IP, 30.2% vs. 21.6%, respectively, p=0.536), median PFS (GP, 4.6 months vs. 5.0 months, respectively, p=0.506; IP, 3.9 months vs. 3.7 months, respectively, p=0.748), or median OS (GP, 18.6 months vs. 11.9 months, respectively, p=0.070; IP, 17.5 months vs. 14.0 months, respectively, p=0.821).
Conclusion
Immunohistochemical analysis of the ERCC1 expression level did not differentiate the efficacy of platinum-based chemotherapy in advanced NSCLC.
Citations
Citations to this article as recorded by
Meta‐Analysis of ERCC1 Protein Expression and Platinum Chemosensitivity in Non‐Small‐Cell Lung Cancer Guoping Li, Dan Cheng, Jamal A. Mahajna Evidence-Based Complementary and Alternative Medicine.2020;[Epub] CrossRef
The role of ERCC1 and AFP gene polymorphism in hepatocellular carcinoma Yu-Liang Huang, Jun-Rong Wu, Min Fang, Hui-Liu Zhao, Zhi-Min Liu, Jian Ye, Ling-Sha Huang, Bo Zhu Medicine.2019; 98(14): e15090. CrossRef