Evaluation of Pneumonitis in a Phase II Study of Consolidation Immunotherapy with Nivolumab and Ipilimumab or Nivolumab Alone following Concurrent Chemoradiotherapy for Unresectable Stage IIIA/IIIB Non-small Cell Lung Cancer (NSCLC)

Abstract

Unresectable stage III Non-Small-Cell-Lung-Cancer (NSCLC) has had an evolving landscape of treatment options with the approvals of immuno-oncologic (IO) therapy. There have been relatively few studies that have evaluated the risk of pneumonitis in patients receiving IO after concurrent chemoradiation treatment (CCRT). This study is to evaluate the relationship of pneumonitis and radiation dose in patients receiving consolidative IO with Nivolumab or Nivolumab plus ipilimumab. Patients with stage III NSCLC who underwent CCRT were enrolled on BTCRC-LUN16-081, a randomized phase II trial assessing the efficacy of nivolumab or nivolumab plus ipilimumab as consolidation therapy. These patients were evaluated for radiation dose parameters and correlation with pneumonitis was examined. After CCRT, patients were enrolled to receive consolidative IO therapy on BTCRC-LUN16-081, and 104 patients had Dose Volume Histogram (DVH) information available for analysis. Of these patients, 58 (55.8%) had stage IIIA and 46 (44.2%) had stage IIIB disease according to 7th edition IASLC. During this period 29 patients (27.9%) had at least grade 2 pneumonitis. Utilizing logistic regression and evaluating different cut offs for lung V20, patients receiving a V20 of greater than 23% had a higher risk of grade 2 or greater pneumonitis (p-value 0.0246, 38% vs. 16%). There was no significant difference in rates of pneumonitis between the two different IO regimens. Traditional lung DVH cutoffs (V5>65%, V20>35%, mean >20 Gy) were not associated with pneumonitis in this study. The use of nivolumab or nivolumab plus ipilimumab after definitive CCRT is safe and effective. Lung V20 > 23% was associated with a higher risk of Grade 2 or higher pneumonitis. Radiation dose constraints for lungs in patients receiving consolidative IO after CCRT should continue to be evaluated and optimized when feasible.