@article{e4c993f7a91b400fab609a46debbb23d,
title = "Impact of smoking status on the relative efficacy of the EGFR TKI/angiogenesis inhibitor combination therapy in advanced NSCLC—a systematic review and meta-analysis",
abstract = "Background: The ETOP 10-16 BOOSTER trial failed to demonstrate a progression-free survival (PFS) benefit for adding bevacizumab to osimertinib in second line. An exploratory subgroup analysis, however, suggested a PFS benefit of the combination in patients with a smoking history and prompted us to do this study. Methods: A systematic review and meta-analysis to evaluate the differential effect of smoking status on the benefit of adding an angiogenesis inhibitor to epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor therapy was carried out. All relevant randomized controlled trials appearing in main oncology congresses or in PubMed as of 1 November 2021 were used according to the Preferred Reporting Items for Systematic Review and Meta-Analyses statement. Primarily PFS according to smoking status, and secondarily overall survival (OS) were of interest. Pooled and interaction hazard ratios (HRs) were estimated by fixed or random effects models, depending on the detected degree of heterogeneity. Bias was assessed using the revised Cochrane tool for randomized controlled trials (RoB 2). Results: Information by smoking was available for 1291 patients for PFS (seven studies) and 678 patients for OS (four studies). The risk of bias was low for all studies. Combination treatment significantly prolonged PFS for smokers [n = 502, HR = 0.55, 95\% confidence interval (CI): 0.44-0.69] but not for nonsmokers (n = 789, HR = 0.92, 95\% CI: 0.66-1.27; treatment-by-smoking interaction P = 0.02). Similarly, a significant OS benefit was found for smokers (n = 271, HR = 0.66, 95\% CI: 0.47-0.93) but not for nonsmokers (n = 407, HR = 1.07, 95\% CI: 0.82-1.42; treatment-by-smoking interaction P = 0.03). Conclusion: In advanced EGFR-non-small-cell lung cancer patients, the addition of an angiogenesis inhibitor to EGFR-tyrosine kinase inhibitor therapy provides a statistically significant PFS and OS benefit in smokers, but not in non-smokers. The biological basis for this observation should be pursued and could determine whether this might be due to a specific co-mutational pattern produced by tobacco exposure.",
keywords = "EGFR mutations, EGFR-TKI, NSCLC, randomised controlled trial, smoking status",
author = "U. Dafni and Soo, \{R. A.\} and S. Peters and Z. Tsourti and P. Zygoura and K. Vervita and Han, \{J. Y.\} and \{de Castro\}, J. and L. Coate and M. Fr{\"u}h and Hashemi, \{S. M. S.\} and E. Nadal and E. Carcereny and Sala, \{M. A.\} and R. Bernab{\'e} and M. Provencio and S. Cuffe and H. Roschitzki-Voser and B. Ruepp and R. Rosell and Stahel, \{R. A.\}",
note = "Funding Information: The authors thank Pilar Garrido (University Hospital Ram{\'o}n y Cajal, Madrid, Spain), Prof. Edward Garon (UCLA Hematology/Oncology Santa Monica, CA), Prof. Hidehito Horinouchi (National Cancer Center, Tokyo, Japan), Prof. Tony Mok (Prince of Wales Hospital, Hong Kong), and Prof. Ben Solomon (Peter MacCallum Cancer Center, Melbourne, Australia) and all participants of the Q\&A discussion of the ESMO Virtual Plenaries for their insightful comments that ultimately gave the idea for this meta-analysis. This work was supported AstraZeneca (grant number: ESR-15-11666) and F. Hoffmann-La Roche (grant number: MO39447). UD reports honorarium as Member of the Tumor Agnostic Evidence Generation working Group of Roche, outside the submitted work. RASo reports advisory role for Amgen, AstraZeneca, Bayer, Bristol Myers Squibb (BMS), Boehringer Ingelheim, Lily, Merck, Novartis, Pfizer, Roche, Taiho, Takeda, and Yuhan and grants from AstraZeneca, Boehringer Ingelheim, outside the submitted work. SP reports grants from Amgen, AstraZeneca, Boehringer Ingelheim, BMS, Clovis, F. Hoffman-La Roche, Illumina, Novartis, Pfizer, Merck Sharp \& Dohme (MSD), personal fees from Amgen, AbbVie, AstraZeneca, Bayer, Biocartis, Boehringer Ingelheim, BMS, Clovis, Daiichi Sankyo, Debiopharm, Eli Lilly, F. Hoffman-La Roche, Foundations Medicine, Illumina, Janssen, Novartis, PharmaMar, Pfizer, Regeneron, Sanofi, Seattle Genetics, Takeda, MSD, Merck Serono, Merrimack, Medscape, Phosphoplatin Therapeutics, Beigene, Imedex, outside the submitted work. JDC reports grants and personal fees from AstraZeneca, BMS, MSD, and Hoffmann-La Roche, personal fees from Bayer, Boehringer Ingelheim, GlaxoSmithKline (GSK), Jansen-Cilag, Lilly, Novartis, Pfizer, and Takeda, outside the submitted work. LC reports advisory role for AstraZeneca, Roche, and Daichi, outside the submitted work. MF reports grants from AstraZeneca and BMS and other support AstraZeneca, BMS, Boehringer Ingelheim, Janssen, MSD, Pfizer, Roche, and Takeda, outside the submitted work. EN reports grants, personal fees, and non-financial support from Roche, personal fees and non-financial support from AstraZeneca, grants, personal fees and non-financial support from BMS, personal fees and non-financial support from MSD, grants and personal fees from Merck Serono, personal fees from Takeda, grants, personal fees, and non-financial support from Pfizer, personal fees from Lilly, personal fees from Bayer, personal fees from Amgen, personal fees from Boehringer Ingelheim, outside the submitted work. EC reports personal fees from AstraZeneca, Amgen, BMS, MSD, and Roche, outside the submitted work. MAS reports advisory role for Roche and Boehringer Ingelheim, speaker role for Pierre Fabre, and travel grants from Roche and PharmaMar, outside the submitted work. RB reports payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Roche, AstraZeneca, BMS, Amgen, and MSD, participation on Data Safety Monitoring Board or Advisory Board for AstraZeneca, BMS, and Roche, outside the submitted work. MP reports grants, personal fees, and non-financial support from AstraZeneca, BMS, and Roche, personal fees from MSD and Takeda, outside the submitted work. SC reports non-financial support from Pfizer, Roche, MSD, BMS, outside the submitted work. RASt reports consultant or advisory role for AstraZeneca, BMS, Boehringer Ingelheim, GSK, MSD, Pfizer, Roche, Sandoz, Seattle Genetics, Takeda, speaker honoraria from Amgen, AstraZeneca, Blueprint, BMS, Boehringer Ingelheim, GSK, MSD, Novartis, Roche, Data Monitoring Committee (DMC) role from Genentech/Roche and Takeda, and financial support for ETOP and IBCSG trials (where he is president), from AstraZeneca, BMS, Daiichi Sankyo, Celgene, Ipsen, Janssen, Mirati, MSD, Novartis, Pfizer, Pierre Fabre, Roche. All other authors have declared no conflicts of interest. Funding Information: This work was supported AstraZeneca (grant number: ESR-15-11666 ) and F. Hoffmann-La Roche (grant number: MO39447 ). Publisher Copyright: {\textcopyright} 2022 The Authors",
year = "2022",
month = jun,
day = "1",
doi = "10.1016/j.esmoop.2022.100507",
language = "English",
volume = "7",
journal = "ESMO open",
issn = "2059-7029",
publisher = "Elsevier B.V.",
number = "3",
}
SDG 3 Good Health and Well-being