IMpower150 Final Exploratory Analyses for Atezolizumab Plus Bevacizumab and Chemotherapy in Key NSCLC Patient Subgroups With EGFR Mutations or Metastases in the Liver or Brain

Naoyuki Nogami*, Fabrice Barlesi, Mark A. Socinski, Martin Reck, Christian A. Thomas, Federico Cappuzzo, Tony S.K. Mok, Gene Finley, Joachim G. Aerts, Francisco Orlandi, Denis Moro-Sibilot, Robert M. Jotte, Daniil Stroyakovskiy, Liza C. Villaruz, Delvys Rodríguez-Abreu, Darren Wan-Teck Lim, David Merritt, Shelley Coleman, Anthony Lee, Geetha ShankarWei Yu, Ilze Bara, Makoto Nishio

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

173 Citations (Scopus)

Abstract

Introduction: Final overall survival (OS) analyses are presented for EGFR mutations and liver or brain metastases subgroups in the phase 3 IMpower150 study (NCT02366143) evaluating atezolizumab plus bevacizumab plus carboplatin and paclitaxel (ABCP) or atezolizumab plus carboplatin and paclitaxel (ACP) versus bevacizumab plus carboplatin and paclitaxel (BCP). Methods: Overall, 1202 patients (intention-to-treat population) with chemotherapy-naive, metastatic, nonsquamous NSCLC were randomized to ABCP, ACP, or BCP. Patients with treated, stable brain metastases were permitted. OS was evaluated in EGFR mutations and baseline liver metastases subgroups; rate and time to development of new brain metastases were evaluated in the intention-to-treat patients. Results: At data cutoff (September 13, 2019; median follow-up, 39.3 mo), OS improvements were sustained with ABCP versus BCP in sensitizing EGFR mutations (all: hazard ratio [HR] = 0.60; 95% confidence interval [CI]: 0.31–1.14; previous tyrosine kinase inhibitor [TKI]: HR = 0.74; 95% CI: 0.38–1.46) and baseline liver metastases (HR = 0.68; 95% CI: 0.45–1.02) subgroups. ACP did not have survival benefit versus BCP in sensitizing EGFR mutations (all: HR = 1.0; 95% CI: 0.57–1.74; previous TKI: HR = 1.22; 95% CI: 0.68–2.22) or liver metastases (HR = 1.01; 95% CI: 0.68–1.51) subgroups. Overall, 100 patients (8.3%) developed new brain metastases. Although not formally evaluated, an improvement toward delayed time to development was found with ABCP versus BCP (HR = 0.68; 95% CI: 0.39–1.19). Conclusions: This final exploratory analysis revealed OS benefits for ABCP versus BCP in patients with sensitizing EGFR mutations, including those with previous TKI failures, and with liver metastases, although these results should be interpreted with caution. The impact of ABCP on delaying the development of new brain lesions requires further investigation.

Original languageEnglish
Pages (from-to)309-323
Number of pages15
JournalJournal of Thoracic Oncology
Volume17
Issue number2
Early online date6 Oct 2021
DOIs
Publication statusPublished - 1 Feb 2022

Bibliographical note

Funding Information:
Disclosure: Dr. Nogami reports receiving personal fees from AstraZeneca , Chugai Pharmaceutical Co., Ltd., Pfizer Japan Inc., Eli Lilly Japan K.K., Ono Pharmaceutical Co., Ltd., Taiho Pharmaceutical Co., Ltd., Merck Sharp & Dohme K.K., Kyowa Hakko-Kirin Co., Ltd., Bristol Myers K.K., and Nippon Boehringer Ingelheim Co., Ltd. outside of the submitted work. Dr. Barlesi reports receiving personal fees from AstraZeneca , Bayer, Bristol Myers Squibb , Boehringer Ingelheim, Eli Lilly Oncology, Roche, Novartis , Merck , Mirati, Merck Sharp & Dohme , Pierre Fabre, Pfizer , Seattle Genetics, and Takeda and institutional fees from AbbVie, ACEA, Amgen, AstraZeneca, Bayer, Bristol Myers Squibb, Boehringer Ingelheim, Eisai, Eli Lilly Oncology, Roche, Genentech, Ipsen, Ignyta, Innate Pharma, Loxo, Novartis, Medimmune, Merck, Merck Sharp & Dohme, Pierre Fabre, Pfizer, Sanofi-Aventis, and Takeda. Dr. Socinski reports receiving grants and personal fees from Genentech, during the conduct of the study; grants and personal fees from AstraZeneca ; personal fees from Merck, Guardant, Bristol Myers Squibb, and Bayer; and grants from Novartis and Spectrum, outside of the submitted work. Dr. Reck reports receiving personal fees from Amgen, AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim, Lilly , Merck , Merck Sharp & Dohme , Novartis , Mirate, Pfizer , and Roche, outside of the submitted work. Dr. Cappuzzo reports receiving personal fees from Roche, during the conduct of the study, and personal fees from AstraZeneca , Bristol Myers Squibb , Merck Sharp & Dohme , Pfizer , Takeda, and Bayer, outside of the submitted work. Dr. Mok reports receiving personal fees from AbbVie , Inc., InMed Medical Communication, MD Health (Brazil), Medscape/WebMD, MoreHealth, PeerVoice, Physicians' Education Resource, P. Permanyer SL, PrIME Oncology, Research to Practice, and Touch Medical Media; personal fees and other fees from ACEA Pharma, Alpha Biopharma Co. Ltd., Amgen, Amoy Diagnostics Co. Ltd., BeiGene, Boehringer Ingelheim, Blueprint Medicines Corporation, CStone Pharmaceuticals, Daiichi Sankyo, Eisai, Fishawack Facilitate Ltd., Gritstone Oncology Inc., Guardant Health, Hengrui Therapeutics, Ignyta Inc., IQVIA, Incyte Corporation, Janssen, Lilly, Loxo-Oncology, Lunit, Inc., Mirati Therapeutics Inc., OrigiMed, Puma Technology Inc., Roche, Sanofi-Aventis R&D, Takeda, and Yuhan Corporation; grants, personal fees, and other fees from AstraZeneca, Bristol Myers Squibb, Merck Serono, Merck Sharp & Dohme, Novartis, and Pfizer, Inc.; other fees from geneDecode, Virtus Medical Group, AstraZeneca PLC, Hutchison Chi-Med, and Sanomics Ltd.; and grants from Clovis Oncology, SFJ Pharmaceuticals, and Xcovery, outside of the submitted work. Dr. Finley reports receiving personal fees and nonfinancial support from Roche, during the conduct of the study, and personal fees from Bayer, Bristol Myers Squibb, and Secura Bio, outside of the submitted work. Dr. Aerts reports receiving personal fees and nonfinancial support from Merck Sharp & Dohme; receiving personal fees from Bristol Myers Squibb, Boehringer Ingelheim, Amphera, Lilly, Takeda, Bayer, Roche, and AstraZeneca, all outside of the submitted work; and having a patent on allogenic tumor cell lysate licensed to amphora (EP2938354A1), a patent combination immunotherapy in cancer (pending), and a patent biomarker for immunotherapy (pending). Dr. Moro-Sibilot reports receiving personal fees and nonfinancial support from Roche, Merck Sharp & Dohme , AstraZeneca , and Bristol Myers Squibb during the conduct of the study, and personal fees from Pfizer , Novartis , Boehringer Ingelheim, Amgen, Lilly, Becton Dickinson, and Takeda, outside of the submitted work. Dr. Jotte reports receiving personal fees from Roche/Genentech, during the conduct of the study, and personal fees from Bristol Myers Squibb outside of the submitted work. Dr. Villaruz reports receiving personal fees from Achilles and institutional research funding from Bristol Myers Squibb, Exelixis, Genentech, AstraZeneca , GSK, Incyte, Rain, Celgene, and Merck , outside of the submitted work. Dr. Rodríguez-Abreu reports receiving personal fees from Merck Sharp & Dohme , Genentech / Roche , Novartis , AstraZeneca , and Lilly, and grants and personal fees from Bristol Myers Squibb , during the conduct of the study. Dr. Lim reports receiving grants and nonfinancial support from Bristol Myers Squibb and Boehringer Ingelheim; nonfinancial support from Ono Pharmaceuticals, Taiho, and AstraZeneca; and personal fees from Novartis, Merck Sharp & Dohme , and Pfizer outside of the submitted work. Mr. Merritt reports having employment by and stock ownership in F. Hoffmann-La Roche, Ltd. Ms. Coleman reports having employment by Genentech, Inc., and stock ownership in F. Hoffman-La Roche, Ltd., Bristol Myers Squibb, Johnson & Johnson, Teva, and Gilead Sciences. Drs. Lee, Yu, and Bara report having employment by Genentech, Inc., and stock ownership in F. Hoffman-La Roche, Ltd. Dr. Shankar reports having previous employment by Genentech, Inc., current employment by Amunix Pharmaceuticals, and a patent (pending) for methods of treating Lung Cancer with a PD-1 axis binding antagonist, an antimetabolite and a platinum agent. Dr. Nishio reports receiving grants and personal fees from Ono Pharmaceutical, Bristol Myers Squibb, Pfizer, Chugai Pharmaceutical, Lilly, Taiho Pharmaceutical, AstraZeneca, Merck Sharp & Dohme, Novartis, Daiichi Sankyo, and Takeda Pharmaceutical Company Ltd., and personal fees from Boehringer Ingelheim, Merck Biopharma, Teijin Pharma Ltd., and AbbVie, outside of the submitted work. The remaining authors declare no conflict of interest.

Funding Information:
This work was supported by F. Hoffmann-La Roche Ltd./Genentech, Inc., a member of the Roche Group. The authors thank the patients and their families. Medical writing assistance for this manuscript was provided by Anusha Bolonna, PhD, and Derrick Afful, PhD, of Health Interactions and funded by F. Hoffmann-La Roche Ltd.

Funding Information:
Disclosure: Dr. Nogami reports receiving personal fees from AstraZeneca, Chugai Pharmaceutical Co., Ltd., Pfizer Japan Inc., Eli Lilly Japan K.K., Ono Pharmaceutical Co., Ltd., Taiho Pharmaceutical Co., Ltd., Merck Sharp & Dohme K.K., Kyowa Hakko-Kirin Co., Ltd., Bristol Myers K.K., and Nippon Boehringer Ingelheim Co., Ltd. outside of the submitted work. Dr. Barlesi reports receiving personal fees from AstraZeneca, Bayer, Bristol Myers Squibb, Boehringer Ingelheim, Eli Lilly Oncology, Roche, Novartis, Merck, Mirati, Merck Sharp & Dohme, Pierre Fabre, Pfizer, Seattle Genetics, and Takeda and institutional fees from AbbVie, ACEA, Amgen, AstraZeneca, Bayer, Bristol Myers Squibb, Boehringer Ingelheim, Eisai, Eli Lilly Oncology, Roche, Genentech, Ipsen, Ignyta, Innate Pharma, Loxo, Novartis, Medimmune, Merck, Merck Sharp & Dohme, Pierre Fabre, Pfizer, Sanofi-Aventis, and Takeda. Dr. Socinski reports receiving grants and personal fees from Genentech, during the conduct of the study; grants and personal fees from AstraZeneca; personal fees from Merck, Guardant, Bristol Myers Squibb, and Bayer; and grants from Novartis and Spectrum, outside of the submitted work. Dr. Reck reports receiving personal fees from Amgen, AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim, Lilly, Merck, Merck Sharp & Dohme, Novartis, Mirate, Pfizer, and Roche, outside of the submitted work. Dr. Cappuzzo reports receiving personal fees from Roche, during the conduct of the study, and personal fees from AstraZeneca, Bristol Myers Squibb, Merck Sharp & Dohme, Pfizer, Takeda, and Bayer, outside of the submitted work. Dr. Mok reports receiving personal fees from AbbVie, Inc., InMed Medical Communication, MD Health (Brazil), Medscape/WebMD, MoreHealth, PeerVoice, Physicians' Education Resource, P. Permanyer SL, PrIME Oncology, Research to Practice, and Touch Medical Media; personal fees and other fees from ACEA Pharma, Alpha Biopharma Co. Ltd., Amgen, Amoy Diagnostics Co. Ltd., BeiGene, Boehringer Ingelheim, Blueprint Medicines Corporation, CStone Pharmaceuticals, Daiichi Sankyo, Eisai, Fishawack Facilitate Ltd., Gritstone Oncology Inc., Guardant Health, Hengrui Therapeutics, Ignyta Inc., IQVIA, Incyte Corporation, Janssen, Lilly, Loxo-Oncology, Lunit, Inc., Mirati Therapeutics Inc., OrigiMed, Puma Technology Inc., Roche, Sanofi-Aventis R&D, Takeda, and Yuhan Corporation; grants, personal fees, and other fees from AstraZeneca, Bristol Myers Squibb, Merck Serono, Merck Sharp & Dohme, Novartis, and Pfizer, Inc.; other fees from geneDecode, Virtus Medical Group, AstraZeneca PLC, Hutchison Chi-Med, and Sanomics Ltd.; and grants from Clovis Oncology, SFJ Pharmaceuticals, and Xcovery, outside of the submitted work. Dr. Finley reports receiving personal fees and nonfinancial support from Roche, during the conduct of the study, and personal fees from Bayer, Bristol Myers Squibb, and Secura Bio, outside of the submitted work. Dr. Aerts reports receiving personal fees and nonfinancial support from Merck Sharp & Dohme; receiving personal fees from Bristol Myers Squibb, Boehringer Ingelheim, Amphera, Lilly, Takeda, Bayer, Roche, and AstraZeneca, all outside of the submitted work; and having a patent on allogenic tumor cell lysate licensed to amphora (EP2938354A1), a patent combination immunotherapy in cancer (pending), and a patent biomarker for immunotherapy (pending). Dr. Moro-Sibilot reports receiving personal fees and nonfinancial support from Roche, Merck Sharp & Dohme, AstraZeneca, and Bristol Myers Squibb during the conduct of the study, and personal fees from Pfizer, Novartis, Boehringer Ingelheim, Amgen, Lilly, Becton Dickinson, and Takeda, outside of the submitted work. Dr. Jotte reports receiving personal fees from Roche/Genentech, during the conduct of the study, and personal fees from Bristol Myers Squibb outside of the submitted work. Dr. Villaruz reports receiving personal fees from Achilles and institutional research funding from Bristol Myers Squibb, Exelixis, Genentech, AstraZeneca, GSK, Incyte, Rain, Celgene, and Merck, outside of the submitted work. Dr. Rodríguez-Abreu reports receiving personal fees from Merck Sharp & Dohme, Genentech/Roche, Novartis, AstraZeneca, and Lilly, and grants and personal fees from Bristol Myers Squibb, during the conduct of the study. Dr. Lim reports receiving grants and nonfinancial support from Bristol Myers Squibb and Boehringer Ingelheim; nonfinancial support from Ono Pharmaceuticals, Taiho, and AstraZeneca; and personal fees from Novartis, Merck Sharp & Dohme, and Pfizer outside of the submitted work. Mr. Merritt reports having employment by and stock ownership in F. Hoffmann-La Roche, Ltd. Ms. Coleman reports having employment by Genentech, Inc., and stock ownership in F. Hoffman-La Roche, Ltd., Bristol Myers Squibb, Johnson & Johnson, Teva, and Gilead Sciences. Drs. Lee, Yu, and Bara report having employment by Genentech, Inc., and stock ownership in F. Hoffman-La Roche, Ltd. Dr. Shankar reports having previous employment by Genentech, Inc., current employment by Amunix Pharmaceuticals, and a patent (pending) for methods of treating Lung Cancer with a PD-1 axis binding antagonist, an antimetabolite and a platinum agent. Dr. Nishio reports receiving grants and personal fees from Ono Pharmaceutical, Bristol Myers Squibb, Pfizer, Chugai Pharmaceutical, Lilly, Taiho Pharmaceutical, AstraZeneca, Merck Sharp & Dohme, Novartis, Daiichi Sankyo, and Takeda Pharmaceutical Company Ltd., and personal fees from Boehringer Ingelheim, Merck Biopharma, Teijin Pharma Ltd., and AbbVie, outside of the submitted work. The remaining authors declare no conflict of interest.

Publisher Copyright:
© 2021 International Association for the Study of Lung Cancer

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