OA03.03 Multi-Institutional Study of Pneumonitis After Treatment with Durvalumab and Chemoradiotherapy for Non-Small Cell Lung Cancer

Consolidation durvalumab improved overall survival (OS) in locally advanced non-small cell lung cancer (LA-NSCLC) patients treated with chemoradiotherapy (CRT) in the PACIFIC trial; however, rates of pneumonitis were increased with durvalumab. We sought to examine real-life outcomes with the PACIFIC paradigm, including pneumonitis rates, management, and the association of pneumonitis with clinical outcomes. Patients with LA-NSCLC treated with CRT followed by durvalumab from October 2017 to June 2019 were identified. We characterized patient demographics, tumor characteristics, radiotherapy parameters, and duration of durvalumab therapy. We examined rates of PFS, OS, pneumonitis, dosing and duration of steroid use, and pneumonitis recurrence following durvalumab re-challenge. A total of 36 patients were included. Median age was 68 (range 38 to 85) with 89% stage III, 3% stage IIB, and 8% with LA-NSCLC recurrent disease. After median follow-up of 10.5 months, 3 and 6-month actuarial grade >2 pneumonitis rates were 25.5% and 29%, respectively, with 2 patients (5.6%) developing grade 3 pneumonitis, and no grade 4 or 5 events. Median time to development of pneumonitis after completion of radiotherapy was 71 days (range 29 to 270 days). Pneumonitis was not significantly associated with differences in patient demographics, tumor histology, chemotherapy, or radiation parameters. Pneumonitis management included prednisone at median dose 60 mg (range 40 to 60 mg) for median taper length of 6 weeks (range 2 to 19 weeks) with durvalumab held for a median of 4.5 weeks (range 2 to 8 weeks). 70% of patients (7/10) were re-challenged with durvalumab, with pneumonitis recurring in 14% of re-challenged patients (1/7). Among patients no longer on immunotherapy, patients who developed pneumonitis had received a similar number of cycles of durvalumab (median 7.5 cycles administered vs. 9 cycles, p=0.32). Median PFS of the cohort was 14.3 months (95% CI, 9.3-19.3). Median OS was not reached, while 12-month and 18-month overall OS rates were 86.4% (63.5-95.8%) and 73.5% (46.1-87.9%). Pneumonitis development did not significantly impact PFS (70% vs. 66% at 9 months for patients who developed pneumonitis vs. patients without pneumonitis, respectively, p=0.94) or OS (100% vs. 83.3% at 12 months, p=0.32). In a multi-institutional cohort of LA-NSCLC patients treated with durvalumab after CRT, approximately 1/3 patients developed symptomatic pneumonitis. Overall survival compared favorably with prior randomized data, and development of pneumonitis did not impact outcomes. In patients with pneumonitis, durvalumab was held for a median 4.5 weeks, and re-initiation was well-tolerated.