Immunotherapy and Stereotactic Radiosurgery for Management of Patients With Lung Cancer Brain Metastases

Purpose: Despite the emerging role of PD-1 pathway inhibitors for patients with advanced lung cancer, there is a paucity of data on the activity of these agents among patients with brain metastases. We investigated the outcomes of PD-1 pathway inhibitors and stereotactic radiosurgery (SRS) for the treatment of patients with lung cancer brain metastases. Methods: We retrospectively reviewed records of non-small cell lung cancer (NSCLC) patients with brain metastases consecutively treated with PD-1 pathway inhibitors and SRS at our institution between 2012 and 2017. Local control (LC), distant brain failure (DBF), and overall survival (OS) were assessed using Kaplan-Meier estimates and Cox regression models. Toxicity was graded according to the Common Criteria for Adverse Events v 4.0. Results: We identified 37 patients treated with SRS to 85 lesions (90.6% intact, 9.4% resected) and a median total of 7 doses of PD-1 pathway inhibitors (83.8% nivolumab, 10.8% atezolizumab, 5.4% pembrolizumab). Most lesions were treated with 18 Gy in a single fraction (n=61, 71.8%). Patients treated with concurrent SRS and PD-1 pathway inhibitors had longer OS and reduced rates of DBF as compared with patients treated with SRS prior to or after PD-1 pathway inhibitors (1-year OS 87.3% vs. 70.0% vs. 0%, p=0.008; 1-year DBF 38.5% vs. 65.8% vs.100%, p=0.042). LC was favorable among lesions treated with SRS concurrent or after PD-1 pathway inhibitors compared to prior to PD-1 pathway inhibitors (1-year LC 100% vs. 72.3%, p=0.016). Three lesions transiently enlarged after SRS and then partially or completely resolved on follow-up imaging. Four patients required steroids for SRS-associated toxicity. No patient had ≥ grade 4 toxicity. Conclusion: Concurrent treatment with SRS and PD-1 pathway inhibitors is associated with favorable overall survival and locoregional disease control for NSCLC patients with brain metastases. This combination of therapy was well tolerated and merits further evaluation in larger cohorts in a prospective setting