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Multicenter Study
. 2023 Apr 1;9(4):527-535.
doi: 10.1001/jamaoncol.2022.7711.

Association of Immune-Related Adverse Events With Efficacy of Atezolizumab in Patients With Non-Small Cell Lung Cancer: Pooled Analyses of the Phase 3 IMpower130, IMpower132, and IMpower150 Randomized Clinical Trials

Mark A Socinski  1 , Robert M Jotte  2   3 , Federico Cappuzzo  4 , Makoto Nishio  5 , Tony S K Mok  6 , Martin Reck  7 , Gene G Finley  8 , Monika D Kaul  9 , Wei Yu  9 , Nindhana Paranthaman  9 , Ilze Bara  9 , Howard J West  10
Affiliations
Multicenter Study

Association of Immune-Related Adverse Events With Efficacy of Atezolizumab in Patients With Non-Small Cell Lung Cancer: Pooled Analyses of the Phase 3 IMpower130, IMpower132, and IMpower150 Randomized Clinical Trials

Mark A Socinski et al. JAMA Oncol. .

Erratum in

Abstract

Importance: Immune-related adverse events (irAEs) arising from immune checkpoint inhibitor (ICI) cancer therapy may potentially predict improved outcomes.

Objective: To evaluate the association between irAEs and atezolizumab efficacy in patients with advanced non-small cell lung cancer (NSCLC) using pooled data from 3 phase 3 ICI studies.

Design, setting, and participants: IMpower130, IMpower132, and IMpower150 were phase 3, multicenter, open-label, randomized clinical trials to evaluate the efficacy and safety of chemoimmunotherapy combinations involving atezolizumab. Participants were chemotherapy-naive adults with stage IV nonsquamous NSCLC. These post hoc analyses were conducted during February 2022.

Interventions: Eligible patients were randomly assigned 2:1 to receive atezolizumab with carboplatin plus nab-paclitaxel, or chemotherapy alone (IMpower130); 1:1 to receive atezolizumab with carboplatin or cisplatin plus pemetrexed, or chemotherapy alone (IMpower132); and 1:1:1 to receive atezolizumab plus bevacizumab plus carboplatin and paclitaxel, atezolizumab plus carboplatin and paclitaxel, or bevacizumab plus carboplatin and paclitaxel (IMpower150).

Main outcomes and measures: Pooled data from IMpower130 (cutoff: March 15, 2018), IMpower132 (cutoff: May 22, 2018), and IMpower150 (cutoff: September 13, 2019) were analyzed by treatment (atezolizumab-containing vs control), irAE status (with vs without), and highest irAE grade (1-2 vs 3-5). To account for immortal bias, a time-dependent Cox model and landmark analyses of irAE occurrence at 1, 3, 6, and 12 months from baseline were used to estimate the hazard ratio (HR) of overall survival (OS).

Results: Of 2503 randomized patients, 1577 were in the atezolizumab-containing arm and 926 were in the control arm. The mean (SD) age of patients was 63.1 (9.4) years and 63.0 (9.3) years, and 950 (60.2%) and 569 (61.4%) were male, respectively, in the atezolizumab arm and the control arm. Baseline characteristics were generally balanced between patients with irAEs (atezolizumab, n = 753; control, n = 289) and without (atezolizumab, n = 824; control, n = 637). In the atezolizumab arm, OS HRs (95% CI) in patients with grade 1 to 2 irAEs and grade 3 to 5 irAEs (each vs those without irAEs) in the 1-, 3-, 6-, and 12-month subgroups were 0.78 (0.65-0.94) and 1.25 (0.90-1.72), 0.74 (0.63-0.87) and 1.23 (0.93-1.64), 0.77 (0.65-0.90) and 1.1 (0.81-1.42), and 0.72 (0.59-0.89) and 0.87 (0.61-1.25), respectively.

Conclusions and relevance: In this pooled analysis of 3 randomized clinical trials, longer OS was observed in patients with vs without mild to moderate irAEs in both arms and across landmarks. These findings further support the use of first-line atezolizumab-containing regimens for advanced nonsquamous NSCLC.

Trial registration: ClinicalTrials.gov Identifiers: NCT02367781, NCT02657434, and NCT02366143.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Socinski reported serving on a speakers bureau and receiving research support from Genentech outside the submitted work. Dr Cappuzzo reported receiving personal fees (advisory boards, lectures, consultancy) from Roche, AstraZeneca, Bristol Myers Squibb (BMS), Pfizer, Takeda, Lilly, Bayer, Amgen, Sanofi, PharmaMar, Novocure, Mirati, Galecto, OSE, and Merck Sharp & Dohme (MSD) outside the submitted work. Dr Nishio reported receiving personal fees (honoraria) from Ono Pharmaceuticals, Chugai Pharmaceutical, Taiho Pharmaceutical, Daiichi Sankyo, Lilly, AstraZeneca, MSD, AbbVie, Takeda, Pfizer, Boehringer Ingelheim, Novartis, Nippon Kayaku, Merck, and Janssen outside the submitted work. Dr Mok reported receiving grants paid to institution from AstraZeneca, BMS, G1 Therapeutics, MSD, Novartis, Pfizer, Roche, SFJ, Takeda, and Xcovery; personal fees (speaker’s fee, consultation fee) from ACEA Pharma, Alpha Biopharma Co Ltd, Amgen, Amoy Diagnostics Co Ltd, BeiGene, Boehringer Ingelheim, BMS, Daiichi Sankyo, Janssen Pharmaceutica NV, Eli Lilly, Lucence Health Inc, Medscape LLC, MSD, MiRXES, Novartis, OrigiMed Co Ltd, Pfizer, PrIME Oncology, Roche Pharmaceuticals/Diagnostics/Foundation One, and Sanofi-Aventis; personal fees (speaker’s fee) from Daz Group, Fishawack Facilitate Ltd, InMed Medical Communication, Jiahui Holdings Co Limited, LiangYiHui Healthcare, MD Health Brazil, Merck Pharmaceuticals HK Ltd, P. Permanyer SL, Taiho Pharmaceutical Co Ltd, and Takeda Oncology; personal fees (consultation fee) from AbbVie, F. Hoffmann-La Roche Ltd/Genentech, Adagene, Berry Oncology, Bridge Biotherapeutics Inc, C4 Therapeutics Inc, Cirina Ltd, Covidien LP, CStone Pharmaceuticals, Curio Science, D3 Bio Ltd, Da Volterra, Eisai, Elevation Oncology, G1 Therapeutics Inc, geneDecode Co Ltd, Gilead Sciences, Guardant Health, Hengrui Therapeutics Inc, HutchMed, Ignyta Inc, Gritstone Oncology Inc, Incyte Corporation, Inivata, IQVIA, Loxo Oncology, Lunit USA, Medscape LLC/WebMD, Merck Serono, Mirati Therapeutics Inc, Omega Therapeutics Inc, OSE Immunotherapeutics, Puma Biotechnology Inc, Qiming Development (HK) Ltd, SFJ Pharmaceutical Ltd, Simcere of America Inc, Synergy Research, Tigermed, Vertex Pharmaceuticals, Virtus Medical Group, Yuhan Corporation, Gritstone Oncology Inc, and Lakeshore Biotech; personal fees (remuneration for serving as a member of board of directors) from AstraZeneca PLC and HutchMed; personal fees (remuneration for serving as chairman) from ACT Genomics-Sanomics Group; and personal fees (remuneration for leadership roles) from Lunit USA, Inc and Aurora outside the submitted work; and being a stock shareholder in AstraZeneca, Aurora Tele-Oncology Ltd, Biolidics Ltd, HutchMed, and ACT Genomics-Sanomics Group. Dr Reck reported receiving personal fees (lectures and consultancy) from Amgen, AstraZeneca, BeiGene, BMS, Boehringer Ingelheim, GlaxoSmithKline, Daiichi Sankyo, Merck, Mirati, MSD, Novartis, Pfizer, Roche, Regeneron, and Sanofi outside the submitted work. Dr Finley reported receiving personal fees from BMS, AstraZeneca, Secura Bio, Bayer, Merck, and Nexus Oncology outside the submitted work. Dr Kaul reported employment and owning stock from F. Hoffmann-La Roche Ltd outside the submitted work. Dr Yu reported employment from Genentech during the conduct of the study. Dr Paranthaman reported employment and receiving grants (employee stock grant) from Genentech outside the submitted work. Dr Bāra reported providing service of medical writing for Genentech during the conduct of the study; and employment from Genentech outside the submitted work. Dr West reported receiving personal fees from Genentech/Roche during the conduct of the study; and personal fees from AstraZeneca, Merck, Genentech/Roche, and Regeneron outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Overall Survival by Immune-Related Adverse Event (irAE) Status in the Atezolizumab-Containing and Control Arms
Kaplan-Meier curves are not adjusted for the timing of irAE onset.
Figure 2.
Figure 2.. Overall Survival Landmarks by Immune-Related Adverse Event (irAE) Status in the 1-Month, 3-Month, 6-Month, and 12-Month Subgroups
Figure 3.
Figure 3.. Overall Survival by Immune-Related Adverse Event (irAE) Grade in the Atezolizumab-Containing Arm in the 1-Month, 3-Month, 6-Month, and 12-Month Subgroups
See this image and copyright information in PMC

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