Background: IMpower133 (NCT02763579), a global Phase I/III, randomized, double-blind, placebo (PBO)-controlled trial, showed that the addition of atezo (anti-PD-L1) to CE for 1L ES-SCLC led to statistically and clinically significant OS and PFS improvement vs CE alone. Here we report updated OS and exploratory analyses. Methods: Pts with untreated ES-SCLC were randomized 1:1 to receive four 21-day cycles of E (100 mg/m2 IV, days 1-3) + C (AUC 5 mg/mL/min IV, day 1) with atezo (1200 mg IV, day 1) or PBO, followed by maintenance therapy with atezo or PBO until intolerable toxicity, progression or loss of clinical benefit. PD-L1 testing was not required for enrollment. Coprimary endpoints were investigator-assessed PFS (RECIST 1.1) and OS. Interim and final OS analyses were planned for ≈240 and ≈306 events, respectively. OS was significant at the interim analysis. Updated OS, exploratory biomarkers and patterns of disease progression were analyzed. Results: 201 and 202 pts were randomized to receive atezo+CE and PBO+CE, respectively. The median follow-up was 22.9 mo and 302 deaths had occurred. Median OS for the atezo and PBO arms was 12.3 and 10.3 mo, respectively (HR, 0.76 [95% CI: 0.60, 0.95]; descriptive P = 0.0154). At the 18-mo landmark, the OS rate was 13% higher with atezo+CE than with PBO+CE (Table). Exploratory analyses showed treatment benefit with atezo+CE regardless of biomarker status. 181 (90.0%) And 194 (96.0%) pts in the atezo+CE and PBO+CE arms, respectively, had RECIST-defined disease progression. Progression at existing, new or existing and new lesions was numerically lower with atezo+CE than with PBO+CE. Common sites of new lesions included the CNS, lung, lymph node and liver, with similar incidences between arms. Conclusion: Adding atezo to CE continued to provide OS improvement for 1L ES-SCLC in an all-comer population. The updated results of IMpower133 further support this regimen for untreated ES-SCLC.

Landmark OSAtezo + CE, n = 201PBO + CE, n = 202
12 Mo, n (%) 93 (51.9) 74 (39.0) 
18 Mo, n (%) 61 (34.0) 39(21.0) 
Median OS in biomarker subgroups Atezo + CE PBO + CE 
ITT (N = 403), mo 12.3 10.3 
HR (95% CI) 0.76 (0.61, 0.96)a 
ITT-BEP (n = 137), mo 9.9 8.9 
HR (95% CI) 0.70 (0.48, 1.02) 
Non-BEP (n = 266), mo 14.6 11.2 
HR (95% CI) 0.81 (0.61, 1.08) 
PD-L1 expression, 1% TC or IC 
< 1% (n = 65), mo 10.2 8.3 
HR (95% CI) 0.51 (0.30, 0.89) 
≥ 1% (n = 72), mo 9.7 10.6 
HR (95% CI) 0.87 (0.51, 1.49) 
PD-L1 expression, 5% TC or IC 
< 5% (n = 108), mo 9.2 8.9 
HR (95% CI) 0.77 (0.51, 1.17) 
≥ 5% (n = 29), mo 21.6 9.2 
HR (95% CI) 0.60 (0.25, 1.46) 
Disease progression at sites, n (%) Atezo + CE PBO + CE 
Existing 116 (57.7) 131 (64.9) 
New 86 (42.8) 99 (49.0) 
Existing and new 42 (20.9) 57 (28.2) 
Landmark OSAtezo + CE, n = 201PBO + CE, n = 202
12 Mo, n (%) 93 (51.9) 74 (39.0) 
18 Mo, n (%) 61 (34.0) 39(21.0) 
Median OS in biomarker subgroups Atezo + CE PBO + CE 
ITT (N = 403), mo 12.3 10.3 
HR (95% CI) 0.76 (0.61, 0.96)a 
ITT-BEP (n = 137), mo 9.9 8.9 
HR (95% CI) 0.70 (0.48, 1.02) 
Non-BEP (n = 266), mo 14.6 11.2 
HR (95% CI) 0.81 (0.61, 1.08) 
PD-L1 expression, 1% TC or IC 
< 1% (n = 65), mo 10.2 8.3 
HR (95% CI) 0.51 (0.30, 0.89) 
≥ 1% (n = 72), mo 9.7 10.6 
HR (95% CI) 0.87 (0.51, 1.49) 
PD-L1 expression, 5% TC or IC 
< 5% (n = 108), mo 9.2 8.9 
HR (95% CI) 0.77 (0.51, 1.17) 
≥ 5% (n = 29), mo 21.6 9.2 
HR (95% CI) 0.60 (0.25, 1.46) 
Disease progression at sites, n (%) Atezo + CE PBO + CE 
Existing 116 (57.7) 131 (64.9) 
New 86 (42.8) 99 (49.0) 
Existing and new 42 (20.9) 57 (28.2) 

BEP, biomarker-evaluable population; ITT, intention-to-treat population.

a Stratified HR. BEP included pts evaluable by PD-L1 IHC using the VENTANA SP263 assay.

Citation Format: Leora Horn, Stephen V. Liu, Aaron S. Mansfield, Tony Mok, Arnaud Scherpereel, Niels Reinmuth, Marina Chiara Garassino, Javier De Castro Carpeno, Raffaele Califano, Makoto Nishio, Francisco Orlandi, Jorge Arturo Alatorre Alexander, Ticiana Leal, Ying Cheng, Jong-Seok Lee, Sivuonthanh Lam, Mark McCleland, Yu Deng, See Phan, Martin Reck. IMpower133: Updated OS and exploratory analyses of first-line (1L) atezolizumab (atezo) + carboplatin (C) + etoposide (E) in extensive-stage SCLC (ES-SCLC) [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr CT220.