Evaluation of Radiation Pneumonitis in a Phase 2 Study of Consolidation Immunotherapy With Nivolumab and Ipilimumab or Nivolumab Alone Following Concurrent Chemoradiation Therapy for Unresectable Stage IIIA/IIIB Non-Small Cell Lung Cancer.

Purpose: The addition of immunotherapy (IO) after concurrent chemoradiation therapy (CCRT) for unresectable non-small cell lung cancer (NSCLC) has become common practice in eligible patients. Approaches to further improve outcomes and reduce treatment-related toxicity for these patients are needed. This study evaluates the risk of radiation pneumonitis after CCRT and its correlation with the radiation dose distribution, IO regimen (nivolumab vs nivolumab plus ipilimumab), and patient demographics across BTCRC-LUN16-081.

Methods and materials: Patients with unresectable stage III NSCLC after completion of CCRT were enrolled in BTCRC-LUN16-081, a randomized phase 2 trial to assess the efficacy and tolerability of consolidative nivolumab versus nivolumab plus ipilimumab for 6 months. Radiation dose parameters, patient demographics, and toxicity events were evaluated among treatment arms for risk and severity of pneumonitis.

Results: One hundred-five patients were enrolled into 2 treatment arms; 54 patients received nivolumab alone, and 51 patients received nivolumab plus ipilimumab. Of these, 104 patients had dose-volume histogram information available. Within this cohort, 65 patients (62.5%) had stage IIIA, and 39 patients (37.5%) had stage IIIB NSCLC disease, per the American Journal Committee on Cancer, seventh edition. During the study, 29 patients (27.9%) were diagnosed with grade 2 or greater pneumonitis. Using logistic regression and evaluating different cutoffs for percentage of normal lung volume receiving at least 20 gy (V20), patients with V20 > 23% demonstrated significantly higher grade 2 or greater pneumonitis rates (37.1% vs 16.2%, P = .031). No significant difference in rates of pneumonitis between arms was identified. Traditional lung dose-volume histogram cutoffs (percentage of normal lung volume receiving at least 5 gy (V5) > 65%, V20 > 35%, and mean > 20 Gy) were not associated with pneumonitis.

Conclusions: In patients receiving nivolumab or nivolumab plus ipilimumab after definitive CCRT, lung V20 > 23% was associated with an increased risk of grade 2 or greater pneumonitis. Radiation dose constraints for lungs in patients receiving consolidative IO after CCRT should continue to be evaluated and optimized when feasible.