Chee Khoon Lee1, Johnathan Man2, Sally Lord3, Matthew Links2, Val Gebski4, Tony Mok5, James Chih-Hsin Yang6. 1. National Health and Medical Research Council Clinical Trials Centre, The University of Sydney, Sydney, Australia; Cancer Care Centre, St. George Hospital, Sydney, Australia. Electronic address: chee.lee@ctc.usyd.edu.au. 2. Cancer Care Centre, St. George Hospital, Sydney, Australia. 3. National Health and Medical Research Council Clinical Trials Centre, The University of Sydney, Sydney, Australia; School of Medicine, The University of Norte Dame, Sydney, Australia. 4. National Health and Medical Research Council Clinical Trials Centre, The University of Sydney, Sydney, Australia. 5. Hong Kong Cancer Institute, Department of Clinical Oncology, Chinese University of Hong Kong, Shatin, People's Republic of China. 6. Graduate Institute of Oncology, National Taiwan University and Department of Oncology, National Taiwan University Hospital, Taipei City, Republic of China.
Abstract
INTRODUCTION: We performed a meta-analysis to assess the role of immune checkpoint inhibitors as second-line therapy in EGFR-mutant advanced NSCLC. METHODS: Randomized trials comparing immune checkpoint inhibitors against chemotherapy were identified. We retrieved the hazard ratio (HR) and 95% confidence interval (CI) for overall survival (OS) of the intention-to-treat population and EGFR mutation-defined subgroups. We used the fixed-effects inverse variance-weighted method to pool estimates of treatment efficacy. Statistical tests were two sided. RESULTS: In the three included studies that compared immune checkpoint inhibitors (nivolumab [n = 292], pembrolizumab [n = 691], and atezolizumab [n =144]) against docetaxel (n = 776), immune checkpoint inhibitors significantly prolonged OS over that with docetaxel overall (n = 1903, HR = 0.68, 95% CI: 0.61-0.77, p < 0.0001) and in the EGFR wild-type subgroup (n = 1362, HR = 0.66, 95% CI: 0.58-0.76, p < 0.0001) but not in the EGFR-mutant subgroup (n = 186, HR = 1.05, 95% CI: 0.70-1.55, p < 0.81; treatment-mutation interaction p = 0.03). CONCLUSION: In EGFR-mutant advanced NSCLC, immune checkpoint inhibitors do not improve OS over that with docetaxel. Mechanisms of acquired resistance to first-line tyrosine kinase inhibitor therapy should be elucidated to guide selection of second-line treatment for these patients.
INTRODUCTION: We performed a meta-analysis to assess the role of immune checkpoint inhibitors as second-line therapy in EGFR-mutant advanced NSCLC. METHODS: Randomized trials comparing immune checkpoint inhibitors against chemotherapy were identified. We retrieved the hazard ratio (HR) and 95% confidence interval (CI) for overall survival (OS) of the intention-to-treat population and EGFR mutation-defined subgroups. We used the fixed-effects inverse variance-weighted method to pool estimates of treatment efficacy. Statistical tests were two sided. RESULTS: In the three included studies that compared immune checkpoint inhibitors (nivolumab [n = 292], pembrolizumab [n = 691], and atezolizumab [n =144]) against docetaxel (n = 776), immune checkpoint inhibitors significantly prolonged OS over that with docetaxel overall (n = 1903, HR = 0.68, 95% CI: 0.61-0.77, p < 0.0001) and in the EGFR wild-type subgroup (n = 1362, HR = 0.66, 95% CI: 0.58-0.76, p < 0.0001) but not in the EGFR-mutant subgroup (n = 186, HR = 1.05, 95% CI: 0.70-1.55, p < 0.81; treatment-mutation interaction p = 0.03). CONCLUSION: In EGFR-mutant advanced NSCLC, immune checkpoint inhibitors do not improve OS over that with docetaxel. Mechanisms of acquired resistance to first-line tyrosine kinase inhibitor therapy should be elucidated to guide selection of second-line treatment for these patients.
Authors: Carminia M Della Corte; Triparna Sen; Carl M Gay; Kavya Ramkumar; Lixia Diao; Robert J Cardnell; Bertha Leticia Rodriguez; C Allison Stewart; Vassiliki A Papadimitrakopoulou; Laura Gibson; Jared J Fradette; Qi Wang; Youhong Fan; David H Peng; Marcelo V Negrao; Ignacio I Wistuba; Junya Fujimoto; Luisa M Solis Soto; Carmen Behrens; Ferdinandos Skoulidis; John V Heymach; Jing Wang; Don L Gibbons; Lauren A Byers Journal: J Thorac Oncol Date: 2020-02-15 Impact factor: 15.609