A Phase 1 Trial of Concurrent or Sequential Ipilimumab, Nivolumab, and Stereotactic Body Radiotherapy in Patients With Stage IV NSCLC Study.

Autor:	Bestvina CM; University of Chicago Comprehensive Cancer Center; Department of Medicine, The University of Chicago, Chicago, Illinois., Pointer KB; Department of Radiation and Cellular Oncology, The University of Chicago, Chicago, Illinois., Karrison T; Department of Public Health Sciences, The University of Chicago, Chicago, Illinois., Al-Hallaq H; Department of Radiation and Cellular Oncology, The University of Chicago, Chicago, Illinois., Hoffman PC; University of Chicago Comprehensive Cancer Center; Department of Medicine, The University of Chicago, Chicago, Illinois., Jelinek MJ; University of Chicago Comprehensive Cancer Center; Department of Medicine, The University of Chicago, Chicago, Illinois., Juloori A; Department of Radiation and Cellular Oncology, The University of Chicago, Chicago, Illinois., Melotek JM; Department of Radiation and Cellular Oncology, The University of Chicago, Chicago, Illinois; Department of Radiation Oncology, Saint Lucie Medical Center, Port St. Lucie, Florida., Murgu S; Department of Anesthesia and Critical Care, The University of Chicago, Chicago, Illinois., Partouche J; Department of Radiation and Cellular Oncology, The University of Chicago, Chicago, Illinois., Vokes EE; University of Chicago Comprehensive Cancer Center; Department of Medicine, The University of Chicago, Chicago, Illinois., Weichselbaum RR; Department of Radiation and Cellular Oncology, The University of Chicago, Chicago, Illinois., Pitroda SP; Department of Radiation and Cellular Oncology, The University of Chicago, Chicago, Illinois., Patel JD; University of Chicago Comprehensive Cancer Center; Department of Medicine, The University of Chicago, Chicago, Illinois; Department of Medicine, Northwestern University, Chicago, Illinois., Chmura SJ; Department of Radiation and Cellular Oncology, The University of Chicago, Chicago, Illinois. Electronic address: schmura@radonc.uchicago.edu.
Jazyk:	angličtina
Zdroj:	Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer [J Thorac Oncol] 2022 Jan; Vol. 17 (1), pp. 130-140. Date of Electronic Publication: 2021 Sep 06.
DOI:	10.1016/j.jtho.2021.08.019
Abstrakt:	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. (Copyright © 2021 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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