IMpower133: Primary efficacy and safety + CNS-related adverse events in a phase I/III study of first-line (1L) atezolizumab + carboplatin + etoposide in extensive-stage SCLC (ES-SCLC)

Abstract

Background: 1L standard‐of‐care treatment (tx) for ES‐SCLC is platinum (carboplatin or cisplatin) + etoposide. Despite high response rates, outcomes remain poor. IMpower133, a global Ph1/3, double‐blind, randomized, placebo (PBO)‐controlled trial evaluated efficacy and safety of adding atezolizumab (atezo; anti‐PD‐L1) or PBO to 1L tx (NCT02763579). Methods: Patient (pts) without prior tx for ES‐SCLC were enrolled. PD‐L1 testing was not required. Randomization was 1:1 to 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 PBO, then maintenance atezo or PBO until PD, unacceptable toxicity or loss of clinical benefit. During maintenance tx, prophylactic cranial irradiation (PCI) was allowed per protocol; definitive thoracic radiation (TR) was not. Co‐primary endpoints were OS and investigatorassessed PFS. Blood tumor mutation burden (bTMB) was an exploratory subgroup analysis using prespecified cutoffs (≥16 vs < 16 and ≥10 vs < 10 mutations/Mb). Results: Adding atezo to carboplatin + etoposide provided a significant improvement in OS and PFS in 1L ES‐SCLC (Table; WCLC 2018:PL02.07). Survival benefits were consistent across key subgroups and prespecified bTMB cutoffs. 44 pts (22 in each arm) received PCI, and 7 pts (3 in atezo arm, 4 in PBO) received TR. Gr 3‐4 tx‐related adverse events (AE) occurred in 56.6% vs 56.1% of pts in atezo vs PBO arms, respectively; serious tx‐related AEs occurred in 22.7% vs 18.9% of pts, respectively. CNS‐related AE rates in patients who had PCI are shown in the table. Conclusions: Adding atezo to carboplatin + etoposide provided a significant improvement in survival in 1L ES‐SCLC in all‐comers. No unexpected safety signals emerged, including in pts who had PCI or TR. Atezo + carboplatin + etoposide may represent a new standard regimen for pts with untreated ES‐SCLC.