Tolerability and Safety of Thoracic Radiation and Immune Checkpoint Inhibitors Among Patients with Lung Cancer

Abstract

Immune checkpoint inhibitors (ICPIs) are changing systemic management of lung cancer. Pneumonitis can lead to dose-limiting toxicity. There are limited published data on the use of thoracic radiation therapy (TRT) before, during, or after administration of these agents. The goal of this study was to assess safety and tolerability among patients receiving TRT within 6 months before or after receipt of ICPIs. For all patients, ICPIs were delivered until disease progression. We identified 29 patients who received TRT between February 2012 and May 2016 to 29 unique intrathoracic sites within 6 months of either single agent ICPI (n=14 anti-PD-1, n=3 anti-PD-L1) or combined ICPIs (n=7 anti-PD-1/CTLA-4, n= 5 anti-PD-L1/CTLA-4). TRT-associated toxicities were defined qualitatively based on careful review of the clinical chart. Kaplan-Meier (KM) estimates of progression-free survival (PFS) and overall survival (OS) were calculated from the date of ICPI initiation. The median age at time of ICPI study enrollment was 64 years (range 41-77) with 16 females (55%). The majority of patients had an ECOG 1 performance status (69%), were of non–small cell lung cancer (NSCLC) histology (79%), with a median of 3 metastatic sites (range 2-8). Fifteen lesions (52%) were treated with TRT concurrent with or after ICPI therapy. The median interval between ICPI and TRT administration was 2.2 months (range 0.4-5.5 month) in lesions treated with TRT before or after ICPI. Median PFS and OS was 3.8 months (1.9, 8-95% CI) and 9.2 months (5.1, not reached-95% CI), respectively, with a median PFS/toxicity follow-up of 6.6 months (range: 0.5-40.4 months). TRT doses ranged between 10 to 70 Gy in 1 to 35 fractions. One patient experienced possible TRT/ICPI related grade 5 pulmonary toxicity 2 weeks following completion of TRT (4 Gy x 5 to right hilum/lung), which was initiated 1 month after the last dose of anti-PD-1 therapy. Two cases of possible grade 3 TRT/ICPI related pneumonitis were noted approximately 2 and 4 months following palliative TRT to the mediastinum and right lower lobe, respectively. In these cases, anti-PD-L1/CTLA-4 and anti-PD-L1 therapy were completed approximately 1 and 2 months before starting RT. Additionally, two cases of grade 2 and grade 3 pneumonitis related to anti-PD-1 agent alone were noted prior to initiation of TRT. In both cases, patients were treated with steroid therapy and subsequently received TRT without additional pulmonary toxicity. In this analysis of TRT delivered among lung cancer patients treated with ICPIs, 3 of 29 patients experienced possible grade ≥3 pneumonitis, which may have been related to TRT while two patients developed pneumonitis from ICPIs alone and were subsequently treated with TRT without increased toxicity. Further prospective safety data is necessary with combination TRT and ICPI therapy.