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

Science and Research

INTRODUCTION: Final overall survival (OS) analyses are presented for EGFR mutations and liver or brain metastases subgroups in the phase III IMpower150 study (NCT02366143) evaluating atezolizumab+bevacizumab+carboplatin/paclitaxel (ABCP) or atezolizumab+carboplatin/paclitaxel (ACP) vs bevacizumab+carboplatin/paclitaxel (BCP). METHODS: Overall, 1202 patients (intention-to-treat [ITT] population) with chemotherapy-naive, metastatic, nonsquamous non-small cell lung cancer were randomized to ABCP, ACP or BCP. Patients with treated, stable brain metastases were permitted. OS was assessed in EGFR mutations and baseline liver metastases subgroups; rate and time to development (TTD) of new brain metastases was assessed in ITT patients. RESULTS: At data cutoff (September 13, 2019; median follow-up, 39.3 months), OS improvements were sustained with ABCP versus BCP in sensitizing EGFR mutations (all: hazard ratio [HR] 0.60; 95% CI: 0.31-1.14; prior 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 show survival benefit versus BCP in sensitizing EGFR mutations (all: HR 1.0; 95% CI: 0.57-1.74; prior 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. While not formally evaluated, an improvement toward delayed TTD was seen with ABCP vs BCP (HR, 0.68; 95% CI: 0.39-1.19). CONCLUSIONS: This final exploratory analysis showed OS benefits for ABCP versus BCP in patients with sensitizing EGFR mutations, including those with prior 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.