Radiotherapy patterns and factors associated with pneumonitis in PACIFIC-R, a real-world study of patients with unresectable stage III non-small-cell lung cancer treated with durvalumab after chemoradiotherapy

Background and purpose: Consolidation durvalumab, standard-of-care treatment for patients with unresectable stage III non-small-cell lung cancer (NSCLC) and no disease progression after chemoradiotherapy, may be associated with pneumonitis. We performed exploratory analyses of radiotherapy patterns and potential risk factors for symptomatic pneumonitis (SP) in PACIFIC-R. Materials and methods: PACIFIC-R is an ongoing, international, observational study based on medical chart data for patients in the durvalumab early access program. Patients with no missing data for candidate SP risk factors were included. SP was defined as a pneumonitis event (any cause) of grade ≥ 2 or requiring corticosteroids. Multivariable logistic regression identified variables associated with SP during durvalumab treatment; sensitivity analyses used a Cox proportional hazards model to account for time to SP. Results: Analyses included 268 patients; most received concurrent (86.6%) versus sequential (13.4%) chemoradiotherapy and intensity-modulated (IMRT; 66.8%) versus three-dimensional conformal (25.7%) radiotherapy, with between-country differences. Patients receiving IMRT were older, more frequently had nonsquamous histology, and had larger tumors. Fifty-two patients (19.4%) had SP during durvalumab treatment. Higher mean lung radiotherapy dose (log transformed) and prior chronic obstructive pulmonary disease (COPD) were associated with higher SP risk, with odds ratios (95% confidence interval [CI]) of 4.73 (1.66-15.07) and 2.60 (1.21-5.65), respectively, and hazard ratios (95% CI) of 3.28 (1.54-6.95) and 1.93 (1.04-3.56), respectively. Conclusions: Concurrent chemoradiotherapy and IMRT were the most common radiotherapy approaches. Higher mean lung radiotherapy dose and prior COPD were associated with higher SP risk during consolidation durvalumab for unresectable stage III NSCLC.