Atezolizumab in Combination With Carboplatin and Nab-Paclitaxel in Advanced Squamous NSCLC (IMpower131): Results From a Randomized Phase III Trial

Abstract

Introduction: Cytotoxic agents have immunomodulatory effects, providing a rationale for combining atezolizumab (anti-programmed death-ligand 1 [anti–PD-L1]) with chemotherapy. The randomized phase III IMpower131 study (NCT02367794) evaluated atezolizumab with platinum-based chemotherapy in stage IV squamous NSCLC. Methods: A total of 1021 patients were randomized 1:1:1 to receive atezolizumabþcarboplatinþpaclitaxel (AþCP) (n ¼ 338), atezolizumabþcarboplatinþnab-paclitaxel (AþCnP) (n ¼ 343), or carboplatinþnab-paclitaxel (CnP) (n ¼ 340) for four or six 21-day cycles; patients randomized to the AþCP or AþCnP arms received atezolizumab maintenance therapy until progressive disease or loss of clinical benefit. The coprimary end points were investigatorassessed progression-free survival (PFS) and overall survival (OS) in the intention-to-treat (ITT) population. The secondary end points included PFS and OS in PD-L1 subgroups and safety. The primary PFS (January 22, 2018) and final OS (October 3, 2018) for AþCnP versus CnP are reported. Results: PFS improvement with AþCnP versus CnP was seen in the ITT population (median, 6.3 versus 5.6 mo; hazard ratio [HR] ¼ 0.71, 95% confidence interval [CI]: 0.60–0.85; p ¼ 0.0001). Median OS in the ITT population was 14.2 and 13.5 months in the AþCnP and CnP arms (HR ¼ 0.88, 95% CI: 0.73–1.05; p ¼ 0.16), not reaching statistical significance. OS improvement with AþCnP versus CnP was observed in the PD-L1–high subgroup (HR ¼ 0.48, 95% CI: 0.29–0.81), despite not being formally tested. Treatment-related grade 3 and 4 adverse events and serious adverse events occurred in 68.0% and 47.9% (AþCnP) and 57.5% and 28.7% (CnP) of patients, respectively. Conclusions: Adding atezolizumab to platinum-based chemotherapy significantly improved PFS in patients with first-line squamous NSCLC; OS was similar between the arms.