Naoyuki Nogami1, Fabrice Barlesi2, Mark A Socinski3, Martin Reck4, Christian A Thomas5, Federico Cappuzzo6, Tony S K Mok7, Gene Finley8, Joachim G Aerts9, Francisco Orlandi10, Denis Moro-Sibilot11, Robert M Jotte12, Daniil Stroyakovskiy13, Liza C Villaruz14, Delvys Rodríguez-Abreu15, Darren Wan-Teck Lim16, David Merritt17, Shelley Coleman17, Anthony Lee17, Geetha Shankar18, Wei Yu17, Ilze Bara17, Makoto Nishio19. 1. National Hospital Organization Shikoku Cancer Center, Matsuyama, Japan. Electronic address: nogami.naoyuki.zx@ehime-u.ac.jp. 2. Assistance Publique Hôpitaux de Marseille, Centre de Recherche en Cancérologie de Marseille (CRCM), Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique (CNRS), Aix-Marseille Université, Marseille, France; Gustave Roussy Cancer Campus, Villejuif, France. 3. AdventHealth Cancer Institute, Orlando, Florida. 4. LungenClinic Grosshansdorf, Airway Research Center North, German Center for Lung Research, Grosshansdorf, Germany. 5. New England Cancer Specialists, Scarborough, Maine. 6. National Cancer Institute, Istituto Di Ricovero E Cura A Cahattere Scientifico (IRCCS) Regina Elena, Rome, Italy. 7. Chinese University of Hong Kong, Hong Kong Special Administrative Region of the People's Republic of China. 8. Allegheny Health Network Cancer Institute, Pittsburgh, Pennsylvania. 9. Erasmus MC University Hospital, Rotterdam, The Netherlands. 10. Instituto Nacional del Tórax, Prosalud Oncología, Santiago, Chile. 11. Centre Hospitalier Universitaire de Grenoble Alpes, Grenoble, France. 12. Rocky Mountain Cancer Centers, Denver, Colorado; US Oncology, Houston, Texas. 13. Moscow City Oncology Hospital No. 62, Moscow, Russia. 14. UPMC Hillman Cancer Center, Pittsburgh, Pennsylvania. 15. Complejo Hospitalario Universitario Insular-Materno Infantil de Gran Canaria, Universidad de Las Palmas de Gran Canaria, Las Palmas de Gran Canaria, Spain. 16. National Cancer Centre Singapore, Singapore. 17. Genentech, Inc., South San Francisco, California. 18. Genentech, Inc., South San Francisco, California; Amunix Pharmaceuticals, South San Francisco, California. 19. The Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan.
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.
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.