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PL02 - Presidential Symposium - Top 5 Abstracts (ID 850)
- Event: WCLC 2018
- Type: Plenary Session
- Track: Advanced NSCLC
- Presentations: 1
- Coordinates: 9/25/2018, 08:15 - 09:45, Plenary Hall
PL02.07 - IMpower 133: Primary PFS, OS and Safety in a PH1/3 Study of 1L Atezolizumab + Carboplatin + Etoposide in Extensive-Stage SCLC (ID 12892)
09:00 - 09:10 | Author(s): Libor Havel
First-line (1L) standard-of-care treatment for extensive-stage small cell lung cancer (ES-SCLC) is platinum (carboplatin or cisplatin) with etoposide. Despite high initial response rates, there has been limited progress in the last two decades and outcomes remain poor with a median overall survival (OS) of ~10 months. IMpower133 (NCT02763579), a global Phase 1/3, double-blind, randomized, placebo-controlled trial evaluated efficacy and safety of adding atezolizumab, a humanized monoclonal anti–PD-L1 antibody, or placebo to 1L carboplatin and etoposide in ES-SCLC.
Patients with measurable (RECIST v1.1) ES-SCLC, ECOG performance status 0 or 1, who had not received prior systemic treatment for ES-SCLC were enrolled. PD-L1 immunohistochemical testing was not required. Patients were randomized 1:1 to receive four 21-day cycles of carboplatin (AUC 5 mg/mL/min IV, Day 1) plus etoposide (100 mg/m2 IV, Days 1-3) with either atezolizumab (1200 mg IV, Day 1) or placebo, followed by maintenance therapy with atezolizumab or placebo until intolerable toxicity or progressive disease per RECIST v1.1. Patients meeting predefined criteria could receive treatment beyond progression. Co-primary endpoints were OS and investigator-assessed progression-free survival (PFS). Adverse events (AEs) were graded per NCI-CTCAE v4.0. Blood-based tumor mutation burden (bTMB) was assessed using prespecified cutoffs of ≥16 vs. <16 and ≥10 vs. <10 mutations/Mb.
In total, 201 patients were randomized to the atezolizumab group, and 202 to the placebo group. Median follow-up was 13.9 months. Median OS was 12.3 months in the atezolizumab group and 10.3 months in the placebo group (hazard ratio [HR] 0.70 [95% confidence interval (CI): 0.54, 0.91; P=0.0069]). Median PFS was 5.2 months and 4.3 months, respectively (HR 0.77 [95% CI: 0.62, 0.96; P=0.017]). OS and PFS benefits were consistent across key patient subgroups. Investigator-assessed confirmed objective response rates were 60.2% and 64.4% in the atezolizumab and placebo groups, respectively; median duration of response, 4.2 and 3.9 months. Exploratory analyses showed OS survival benefits in subgroups above and below prespecified bTMB cutoffs. Grade 3-4 treatment-related AEs were reported in 56.6% vs. 56.1% patients in atezolizumab vs. placebo groups, respectively; serious treatment-related AEs occurred in 22.7% and 18.9% patients, respectively.
Addition of atezolizumab to carboplatin and etoposide provided a significant improvement in OS and PFS in 1L ES-SCLC in an all-comer patient population. No unexpected safety signals were identified. Atezolizumab plus carboplatin and etoposide may represent a new standard regimen for patients with untreated ES-SCLC.a9ded1e5ce5d75814730bb4caaf49419