Abstract CT216: IMpower150 final analysis: Efficacy of atezolizumab (atezo) + bevacizumab (bev) and chemotherapy in first-line (1L) metastatic nonsquamous (nsq) non-small cell lung cancer (NSCLC) across key subgroups
Authors: Socinski Mark A. , Mok Tony S. , Nishio Makoto , Jotte Robert M. , Cappuzzo Federico , Orlandi Francisco , Stroyakovskiy Daniil , Nogami Naoyuki , Rodriguez-Abreu Delvys , Moro-Sibilot Denis , Thomas Christian A. , Barlesi Fabrice , Finley Gene , Kong Shengchun , Liu Xiaoyan , Lee Anthony , Coleman Shelley , Shankar Geetha , Reck Martin 
Published: September 2020

Background: The Ph III IMpower150 study (NCT02366143) showed PFS and OS benefit with atezo + bev + carboplatin (carbo) + paclitaxel (pac; ABCP; Arm B) vs bev + carbo + pac (BCP; Arm C) as 1L treatment (tx) for patients (pts) with metastatic nsq NSCLC. Clinical benefit was also seen in pts with EGFR-mutant or ALK-positive (EGFR/ALK+) tumors. We report the final efficacy analyses from IMpower150, including those of the experimental tx arm evaluating atezo + carbo + pac (ACP; Arm A) vs Arm C.

Methods: The randomized, open-label, Ph III IMpower150 study evaluated ACP (Arm A) or ABCP (Arm B) vs BCP (Arm C) in pts with metastatic nsq NSCLC (N = 1202). Key eligibility criteria included no prior chemotherapy, measurable disease per RECIST 1.1 and ECOG PS 0-1. Pts were stratified by sex, baseline liver metastases (mets) and PD-L1 expression. Coprimary endpoints were investigator-assessed PFS and OS in ITT wild-type (WT; no EGFR or ALK genetic alterations) pts. Secondary endpoints included PFS and OS in the ITT and PD-L1 expression subgroups.

Results: With a minimum follow-up of 32.4 mo (data cutoff: Sep 13, 2019), median OS in ITT-WT pts was 19.0 mo in Arm A vs 14.7 mo in Arm C (HR, 0.84; 95% CI: 0.71, 1.00; Table). OS improvement in the TC1/2/3 or IC1/2/3-WT PD-L1 subgroup was seen in Arm A vs C; no improvement was seen in the TC0 and IC0-WT subgroup. In pts with EGFR/ALK+ tumors and pts with baseline liver mets, OS was comparable in Arms A and C; continued OS benefit in these subgroups was seen in Arm B vs C. The safety profile of each regimen was consistent with previously reported data at the second interim OS analysis (data cutoff: Jan 22, 2018).

Arm A vs Arm CArm B vs Arm CaOS HR (95% CI)Median OS, moOS HR (95% CI)Median OS, moITTb (n = 402 [Arm A]; 400 [Arm B]; 400 [Arm C])0.86 (0.73, 1.01)19.0 vs 15.00.80 (0.68, 0.95)19.8 vs 15.0ITT-WTb (n = 350 [Arm A]; 359 [Arm B]; 338 [Arm C])0.84 (0.71, 1.00)19.0 vs 14.70.80 (0.67, 0.95)19.5 vs 14.7TC1/2/3 or IC1/2/3-WT (n = 185 [Arm A]; 192 [Arm B]; 165 [Arm C])0.71 (0.55, 0.91)24.4 vs 16.00.73 (0.57, 0.94)22.5 vs 16.0TC0 and IC0-WT (n = 164 [Arm A]; 167 [Arm B]; 173 [Arm C])0.96 (0.76, 1.22)14.8 vs 14.10.90 (0.71, 1.14)16.9 vs 14.1EGFR/ALK+ (n = 52 [Arm A]; 41 [Arm B]; 62 [Arm C])1.03 (0.67, 1.58)21.2 vs 17.50.77 (0.48, 1.26)25.3 vs 17.5EGFR sensitizing (n = 33 [Arm A]; 26 [Arm B]; 32 [Arm C])1.00 (0.57, 1.74)19.0 vs 18.10.60 (0.31, 1.14)29.4 vs 18.1Liver mets ITT (n = 52 [Arm A]; 52 [Arm B]; 57 [Arm C])1.01 (0.68, 1.51)7.7 vs 9.10.67 (0.45, 1.02)13.2 vs 9.1IC, tumor-infiltrating immune cells; TC, tumor cells. TC1/2/3 or IC1/2/3 = TC ≥ 1% or IC ≥ 1% PD-L1. TC0 and IC0 = TC &lt; 1% and IC &lt; 1% PD-L1.aAnalysis considered final at second OS interim analysis; data shown are for descriptive purposes only.bStratified analysis.

Conclusions: At the final OS analysis, IMpower150 showed numerically but not statistically significant OS improvement in Arm A vs C. Final analysis data from IMpower150 continue to show OS benefit with 1L ABCP in nsq NSCLC, including in key subgroups (sensitizing EGFR mutations, liver mets).

Citation Format: Mark A. Socinski, Tony S. Mok, Makoto Nishio, Robert M. Jotte, Federico Cappuzzo, Francisco Orlandi, Daniil Stroyakovskiy, Naoyuki Nogami, Delvys Rodriguez-Abreu, Denis Moro-Sibilot, Christian A. Thomas, Fabrice Barlesi, Gene Finley, Shengchun Kong, Xiaoyan Liu, Anthony Lee, Shelley Coleman, Geetha Shankar, Martin Reck. IMpower150 final analysis: Efficacy of atezolizumab (atezo) + bevacizumab (bev) and chemotherapy in first-line (1L) metastatic nonsquamous (nsq) non-small cell lung cancer (NSCLC) across key subgroups [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 CT216.