Nivolumab and ipilimumab with concurrent stereotactic radiosurgery for intracranial metastases from non-small cell lung cancer: analysis of the safety cohort for non-randomized, open-label, phase I/II trial

作者：Mehmet Altan, Yan Wang, Juhee Song, James W. Welsh, Chad Tang, Nandita Guha‐Thakurta, George R. Blumenschein, Brett W. Carter, Jeffrey S. Wefel, Amol J. Ghia, D.N. Yeboa, Mary Frances McAleer, Caroline Chung, Kristina D. Woodhouse, Susan L. McGovern, Chenyang Wang, Betty Y.S. Kim, Jeffrey S. Weinberg, Tina M. Briere, Yasir Y. Elamin, Xiuning Le, Tina Cascone, Marcelo V. Negrão, Ferdinandos Skoulidis, Renata Ferrarotto, John V. Heymach, Jing Li · 发表于：Journal for ImmunoTherapy of Cancer · 年份：2023 · DOI：10.1136/jitc-2023-006871 · 被引用次数：28 · 研究领域：Brain Metastases and Treatment、Cancer Immunotherapy and Biomarkers、Lung Cancer Research Studies

BACKGROUND: Up to 20% of patients with non-small cell lung cancer (NSCLC) develop brain metastasis (BM), for which the current standard of care is radiation therapy with or without surgery. There are no prospective data on the safety of stereotactic radiosurgery (SRS) concurrent with immune checkpoint inhibitor therapy for BM. This is the safety cohort of the phase I/II investigator-initiated trial of SRS with nivolumab and ipilimumab for patients with BM from NSCLC. PATIENTS AND METHODS: This single-institution study included patients with NSCLC with active BM amenable to SRS. Brain SRS and systemic therapy with nivolumab and ipilimumab were delivered concurrently (within 7 days). The endpoints were safety and 4-month intracranial progression-free survival (PFS). RESULTS: Thirteen patients were enrolled in the safety cohort, 10 of whom were evaluable for dose-limiting toxicities (DLTs). Median follow-up was 23 months (range 9.7-24.3 months). The median interval between systemic therapy and radiation therapy was 3 days. Only one patient had a DLT; hence, predefined stopping criteria were not met. In addition to the patient with DLT, three patients had treatment-related grade ≥3 adverse events, including elevated liver function tests, fatigue, nausea, adrenal insufficiency, and myocarditis. One patient had a confirmed influenza infection 7 months after initiation of protocol treatment (outside the DLT assessment window), leading to pneumonia and subsequent death from hemophago...