Phase II Randomized Study of Maintenance Atezolizumab Versus Atezolizumab Plus Talazoparib in Patients With SLFN11 Positive Extensive-Stage SCLC: S1929
- PMID: 39505259
- DOI: 10.1016/j.jtho.2024.10.021
Phase II Randomized Study of Maintenance Atezolizumab Versus Atezolizumab Plus Talazoparib in Patients With SLFN11 Positive Extensive-Stage SCLC: S1929
Abstract
Objective: To evaluate whether the addition of a poly (adenosine diphosphate-ribose) polymerase inhibitor talazoparib to maintenance immune checkpoint inhibitor atezolizumab after frontline chemoimmunotherapy improved outcomes in patients with Schlafen 11 (SLFN11)-positive extensive-stage SCLC (ES-SCLC).
Methods: Patients with newly diagnosed SLFN11 expressing (H-score ≥ 1, evaluated centrally) ES-SCLC were randomized to maintenance atezolizumab (A) versus atezolizumab plus talazoparib (AT) after frontline chemotherapy plus atezolizumab. The primary objective was to compare progression-free survival (PFS) using a one-sided 10% level stratified log-rank test. Secondary endpoints included objective response rate, overall survival, and toxicity. The target sample size was 84 eligible patients.
Results: From June 15, 2020, to December 15, 2022, 106 eligible patients were randomized (54 to AT and 52 to A). Progression-free survival was improved with AT versus A (hazard ratio = 0.66, 80% confidence interval: 0.50-0.86, one-sided p = 0.019) with a median PFS of 2.9 and 2.4 months; overall survival was not different between groups (hazard ratio = 0.98, 80% confidence interval: 0.71-1.36, one-sided p = 0.47). Grade 3 and higher non-hematologic treatment-related adverse events occurred in 17% of patients with AT and 14% of patients with A. Grade 3 and higher hematological treatment-related adverse events were more common in AT (50%) than in A (4%) (p < 0.001).
Conclusion: Maintenance AT improved PFS in patients with SLFN11-positive ES-SCLC that did not progress after initial chemo-immunotherapy. Hematologic toxicity, primarily grade 3 anemia, was increased with AT, as expected. Prospective biomarker selection was demonstrated, paving the way for future evaluation of novel therapies in molecularly defined SCLC populations.
Keywords: Maintenance; PARP inhibitors; SLFN11; Small Cell Lung Cancer.
Copyright © 2024. Published by Elsevier Inc.
Conflict of interest statement
Disclosure Dr. Abdel Karim reports research funding to institution from Pfizer, BMS and Exelixis; Consulting fees from Amgen, Jazz Therapeutics, Astra Zeneca, BMS, Sanofi, Innovent, Janssen, MERCK, Novocure, Pfizer, G1 Therapeutics, Immunogen, AbbVie. Jieling Miao reports none. Dr. Karen Reckamp reports research funding to institution from Genentech; Blueprint; Daiichi Sankyo; Elevation Oncology; and Janssen. Consulting fees from Amgen, AstraZeneca, Blueprint, Daiichi Sankyo, Genentech, GlaxoSmithKline, Janssen, Lilly, Mirati, Novartis, Novocure (Consulting honoraria to self). Dr. Gay reports research funding to institution from AstraZeneca, and Daiichi-Sankyo. Consulting fees from AstraZeneca, Catalyst, Insights Driven Research, Kisoji Biotechnology, and WC Communications (to self). Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Academy for Continued Healthcare Learning, Aptitude Health, AstraZeneca, Beigene, Clinical Education Alliance, Dava Oncology, IDEOlogy, Jazz Pharmaceuticals, OncLive, PeerView Institute, Physicians’ Education Resource, and Targeted Healthcare (Speaking fees/honoraria to self). Support for attending meetings and/or travel to ASTRO, IASLC, OncLive from Roche/Genentech. Patent: US Patent No. 11,732,306. Molecular Subtyping of Small Cell Lung Cancer to Predict Therapeutic Responses (issued). Dr. Byers reports consulting fees from Abbvie, Daiichi Sankyo, Amgen, Genentech, Arrowhead Pharmaceuticals, Jazz Pharmaceuticals, AstraZeneca, Merck Sharp & Dohme, BeiGene, Novartis, Boehringer Ingelheim, Puma Biotechnology and Chugai Pharm. Patents: Molecular subtyping of small cell lung cancer to predict therapeutic responses (US Patent No.: 11,732,306; Priority Date 9/3/2019; Issue Date 8/22/2023); and Methods and systems for diagnosis, classification, and treatment of small cell lung cancer and other high grade neuroendocrine carcinomas (Priority date: 3/3/2021). Dr. Yingqi Zhao reports none. Dr. Redman reports none. Dr. Carrizosa reports research grants from Merck Research (to Institution); Scorpion Therapeutics (to institution);Takeda (to institution); Bicara (to institution); Elevation Oncology (to institution). Dr. Wang reports none. Dr. Petty reports consulting fees from Amgen (Payments to self, <$5,000); Mirati Therapeutics (Payments to self, <$5,000); Jazz Pharmaceuticals (Payments to self, <$5,000). Payment from Jazz Pharmaceuticals for writing and editorial assistance. Dr. Mehta reports consulting fees from Cardinal Health, and Cornerstone Specialty Network. Dr. Faller reports none. Dr. Agamah reports none. Dr. Kasbari reports payment to self as speaker. Board Member (unpaid) for UNC Health Wayne Hospital. Dr. Malisetti reports none. Dr. Kumar reports none. Dr. Schallenkamp reports none. Dr. Alluri reports none. Dr. Gray reports grants from AstraZeneca; Boehringer Ingelheim; Bristol-Myers Squibb; Eli Lilly; EMD Serono-Merck KGaA; Genentech; Gilead Sciences: G1 Therapeutics; Ludwig Institute of Cancer Research; Merck & Co, Inc; Novartis; Panbela Therapeutics; Pfizer; and Regeneron. Consulting fees from AbbVie; AstraZeneca; Blueprint Medicines; Coherus; Daiichi Sankyo; EMD Serono; Genentech; Gilead Sciences, Inc; IDEOlogy Health; Janssen Scientific Affairs, LLC; Jazz Pharmaceuticals; Loxo Oncology Inc; Merck & Co, Inc; Novartis; OncoCyte Biotechnology; Regeneron; Spectrum ODAC; Takeda Pharmaceuticals; Triptych Health Partners; and Zai Lab (US) LLC, Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from AbbVie; AstraZeneca; Blueprint Medicines; Coherus; Daiichi Sankyo; EMD Serono; Genentech; Gilead Sciences, Inc; IDEOlogy Health; Janssen Scientific Affairs, LLC; Jazz Pharmaceuticals; Loxo Oncology Inc; Merck & Co, Inc; Novartis; OncoCyte Biotechnology; Regeneron; Spectrum ODAC; Takeda Pharmaceuticals; Triptych Health Partners; and Zai Lab (US) LLC. Support for attending meetings and/or travel from AbbVie; OncoCyte; Coherus; and Spectrum Pharmaceuticals. Participation on a Data Safety Monitoring Board or Advisory Board for AbbVie; AstraZeneca; Blueprint Medicines; Coherus; Daiichi Sankyo; EMD Serono; Genentech; Gilead Sciences, Inc; IDEOlogy Health; Janssen Scientific Affairs, LLC; Jazz Pharmaceuticals; Loxo Oncology Inc; Merck & Co, Inc; Novartis; OncoCyte Biotechnology; Regeneron; Spectrum ODAC; Takeda Pharmaceuticals; Triptych Health Partners; and Zai Lab (US) LLC. Leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid for ASCO Board of Directors Member; ASCO Education Committee Ex-Chair; SWOG Lung Committee Chair; IASLC Board of Directors Member. Dr. Kelly reports royalty payment up to date. Leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid: CEO – IASLC.