Implications of pneumonitis after chemoradiation and durvalumab for locally advanced non-small cell lung cancer

Background: Consolidation durvalumab improved overall survival (OS) in locally advanced non-small cell lung cancer (LA-NSCLC) treated with chemoradiotherapy (CRT) in the PACIFIC trial; however, pneumonitis was increased with durvalumab. We sought to examine real-world outcomes with the PACIFIC paradigm, especially factors associated with pneumonitis, using a multi-institutional review. Methods: Patients with LA-NSCLC treated with CRT followed by durvalumab from January 2017-February 2019 were identified at 2 institutions. We characterized demographics, tumor factors, radiotherapy, and duration of durvalumab. We examined pneumonitis outcomes including re-challenge success, with secondary endpoints of progression-free survival (PFS) and OS. Results: Thirty-four patients were included with median follow-up of 12 months (range, 3 to 20 months); 94% had stage III disease. The cumulative grade >2 pneumonitis rate was 26.5% with 2 patients developing grade 3 pneumonitis and no grade 4/5 events. Median time to pneumonitis after RT was 2.4 months (range, 0 to 4.9 months). Pneumonitis management included median prednisone dose of 60 mg for median taper of 6 weeks with durvalumab held for median of 4.5 weeks (range, 2 to 8 weeks); 70% of pneumonitis patients received durvalumab re-challenge, with pneumonitis recurring in 14% of patients. 3-month and 6-month pneumonitis-free-survival were 76.9% and 73.6%, respectively; 9- and 12-month OS were 96% (75.1-99.8%), 86.6% (63.5-95.5%), respectively; 9- and 12-month PFS were 68% (47.5-82.5%), 48.7% (25.3-68.3%). Pneumonitis development did not significantly impact PFS or OS (P>0.05). Conclusions: Among LA-NSCLC patients treated with CRT followed by consolidation durvalumab, more than 25% developed symptomatic pneumonitis. In this small case series, pneumonitis did not appear to negatively impact survival, and durvalumab re-challenge appeared feasible after pneumonitis treatment with steroids.