@article{d31b256e7c44482abd980ead8f19115b,
title = "A Phase 1 Trial of Concurrent or Sequential Ipilimumab, Nivolumab, and Stereotactic Body Radiotherapy in Patients With Stage IV NSCLC Study",
abstract = "Introduction: Previous studies have evaluated stereotactic body radiotherapy (SBRT) in oligometastatic patients with NSCLC, including multimodality treatment with anti–programmed cell death protein-1 monotherapy. Questions remain regarding the timing of SBRT and immunotherapy, safety with dual checkpoint blockade, and the utility in widely metastatic patients. This randomized phase 1 trial combined nivolumab and ipilimumab with sequential or concurrent multisite SBRT in patients with stage IV NSCLC to evaluate safety and obtain preliminary activity data. Methods: Treatment-naive patients with metastatic NSCLC were randomized to concurrent (SBRT with immunotherapy) or sequential (SBRT followed by immunotherapy) treatment. A maximum of four treatment fields received SBRT. Nivolumab and ipilimumab were continued until clinical progression, development of toxicity, or after 2 years. Dose-limiting toxicity was defined as greater than or equal to grade 3 toxicity to the relevant organ system attributed to SBRT and immunotherapy occuring within 3 months. Results: A total of 37 patients were assessable. No dose-limiting toxicity occurred in the concurrent cohort (n = 18). The sequential cohort required a dose reduction in the central lung group owing to two grade 4 pneumonitis events (2 of 19). Overall best response was as follows: 5.4% (2 of 37) complete response, 40.5% (15 of 37) partial response, 16.2% (6 of 37) stable disease, and 37.8% (14 of 37) progressive disease. Median progression-free survival was 5.8 months (95% confidence interval: 3.6–11.4 mo), with median follow-up of 17.0 months. Median overall survival was not reached. Conclusions: Concurrent nivolumab, ipilimumab, and SBRT were not more toxic than sequential therapy, and multisite SBRT was well tolerated in widely metastatic patients. Multimodality therapy resulted in durable metastasis control and encouraging early overall survival.",
keywords = "Immunotherapy, Ipilimumab, Nivolumab, Non–small cell lung cancer, Stereotactic body radiotherapy",
author = "Bestvina, {Christine M.} and Pointer, {Kelli B.} and Theodore Karrison and Hania Al-Hallaq and Hoffman, {Philip C.} and Jelinek, {Michael J.} and Aditya Juloori and Melotek, {James M.} and Septimiu Murgu and Julien Partouche and Vokes, {Everett E.} and Weichselbaum, {Ralph R.} and Pitroda, {Sean P.} and Patel, {Jyoti D.} and Chmura, {Steven J.}",
note = "Funding Information: This study was financially supported by Bristol-Myers Squibb (BMS), but the study conduct, including toxicity monitoring, was done by the study team of The University of Chicago Medicine . BMS was not involved in the initial design of the study and in the conduct, collection, management, analysis, and interpretation of the data. BMS or its employees were not involved in the preparation, review, or approval of the manuscript. The authors thank the patients and their families for their participation in the study. Funding Information: Disclosures: Dr. Bestvina reports serving in a consulting or advisory role for AbbVie, AstraZeneca, Genentech, Pfizer, Seattle Genetics, and Takeda. Dr. Al-Hallaq reports receiving grants from Varian Medical Systems and royalties from patents licensed through the university from The University of Chicago outside of the submitted work. Dr. Murgu is an advisor for Olympus America, Medtronic, Johnson and Johnson, ERBE, Boston Scientific, Cook Inc., and Pinnacle Biologics. Dr. Vokes has served as an advisor for AbbVie, AstraZeneca, BeiGene, BioNTech, Eli Lilly, ED Serono, Genentech/Roche, GlaxoSmithKline, Merck, and Novartis. Dr. Weichselbaum reports having stock and other ownership interests with Boost Therapeutics, ImmVira LLC, Reflexion Pharmaceuticals, Coordination Pharmaceuticals Inc., Magi Therapeutics, and Oncosenescence; serving in a consulting or advisory role for Aettis Inc., AstraZeneca, Coordination Pharmaceuticals, Genus, Merck Serono S.A., NanoProteagen, NKMax America Inc., Shuttle Pharmaceuticals, and Highlight Therapeutics, S.L.; having research grants with Varian and Regeneron; and receiving compensation including travel, accommodations, or expense reimbursement from AstraZeneca, Boehringer Ingelheim Ltd. and Merck Serono S.A. Dr. Pitroda has patents outside of the submitted work. Dr. Patel serves as an advisor for AstraZeneca, Takeda, and Genentech and receives research funding from Bristol-Myers Squibb (institution). Dr. Chmura reports participating in the advisory boards for Genentech and AstraZeneca; receiving research support from Bristol-Myers Squibb, Merck, EMD Serono, and AstraZeneca; and having his spouse who works for Astellas. The remaining authors declare no conflict of interest.This study was financially supported by Bristol-Myers Squibb (BMS), but the study conduct, including toxicity monitoring, was done by the study team of The University of Chicago Medicine. BMS was not involved in the initial design of the study and in the conduct, collection, management, analysis, and interpretation of the data. BMS or its employees were not involved in the preparation, review, or approval of the manuscript. The authors thank the patients and their families for their participation in the study. Publisher Copyright: {\textcopyright} 2021 International Association for the Study of Lung Cancer",
year = "2022",
month = jan,
doi = "10.1016/j.jtho.2021.08.019",
language = "English (US)",
volume = "17",
pages = "130--140",
journal = "Journal of Thoracic Oncology",
issn = "1556-0864",
publisher = "International Association for the Study of Lung Cancer",
number = "1",
}
