Safety of Combined PD-1 Pathway Inhibition and Intracranial Radiation Therapy in Non-Small Cell Lung Cancer

Abstract

Introduction: Intracranial metastases are a common cause of morbidity and mortality in patients with advanced non-small cell lung cancer (NSCLC), and are frequently managed with radiation therapy (RT). The safety of cranial RT in the setting of treatment with immune checkpoint inhibitors (ICIs) has not been established. Methods: We identified advanced NSCLC patients with brain metastases who received cranial RT and were treated with or without PD-1/PD-L1 inhibitors between August 2013 and September 2016. RT-related adverse events (AEs) were retrospectively evaluated and analyzed according to ICI treatment status, cranial RT type, and timing of RT with respect to ICI. Results: Of 163 patients, 50 (31%) patients received ICIs while 113 (69%) were ICI-naive. Overall, 94 (58%), 28 (17%) and 101 (62%) patients received stereotactic radiosurgery (SRS), partial brain irradiation (PBI), and/or whole brain RT (WBRT), respectively. Fifty percent of patient received >1 radiation course. We observed no significant difference in rates of all-grade AEs and grade ≥3 AEs between ICI-naive and ICI-treated patients across different cranial RT types (grade ≥3 AEs: 8% ICI- vs. 9% ICI+ for SRS [P=1.00]; 8% ICI- vs. 10% ICI+ for WBRT [P=0.71]). Additionally, there was no difference in AE rates based on the timing of ICI administration with respect to RT. Conclusions: Treatment with ICI and cranial RT was not associated with a significant increase in RT-related AEs, suggesting that use of PD-1/PD-L1 inhibitors in patients receiving cranial RT may have an acceptable safety profile. Nonetheless, additional studies are needed to validate this approach.