IMpower133: Updated overall survival (OS) analysis of first-line (1L) atezolizumab (atezo) + carboplatin + etoposide in extensive-stage SCLC (ES-SCLC)

Abstract

Background: IMpower133 (NCT02763579), a global Phase I/III, double- blind, randomized, placebo-controlled trial, showed that adding atezo (anti-PD-L1) to 1L carboplatin + etoposide for ES-SCLC led to a statistically and clinically significant improvement in OS and progression-free survival (PFS) vs carboplatin + etoposide alone. This combination was US FDA-approved in March 2019. Here we present an exploratory updated OS analysis of IMpower133. Methods: Patients (pts) without prior systemic tx for ES-SCLC were enrolled. PD-L1 testing was not required for enrolment eligibility, but tissue was collected when possible. Pts were randomised 1:1 to receive four 21-day cycles of carboplatin (AUC 5 mg•mL/min IV, Day 1) + etoposide (100 mg/m2 IV, Days 1-3) with either atezo (1200 mg IV, Day 1) or placebo (PBO), then maintenance therapy with atezo or PBO until intolerable toxicity or progression. Pts meeting predefined criteria could receive tx beyond progression. Coprimary endpoints were OS and investigator-assessed PFS. OS interim and final analyses were planned for ≈ 240 and ≈ 306 OS events, respectively. Since OS was statistically significant at the interim analysis, an exploratory updated OS analysis was conducted, and exploratory biomarker analyses are in progress. Results: 201 pts were randomized to the atezo group and 202 to the PBO group. At this updated analysis, 302 OS events had been observed. Median follow-up was 22.9 mo. Median OS remained 12.3 mo in the atezo group and 10.3 mo in the PBO group (HR, 0.76 [95% CI: 0.60, 0.95]; descriptive P = 0.0154). Cumulative survival rates at 6, 12 and 18 mo were 86%, 52% and 34% in the atezo group, and 83%, 39% and 21% in the PBO group, respectively. Other efficacy analyses, including by PD-L1 status, will be presented. Conclusion: The addition of atezo to carboplatin and etoposide continued to provide improvement in OS for 1L ES-SCLC. These results further support this regimen as the new standard of care for untreated ES-SCLC.