Impact of durvalumab re-administration after moderate symptomatic pneumonitis in locally advanced non-small cell lung cancer

Background

The standard of care for unresectable locally advanced non-small cell lung cancer (LA-NSCLC) includes post-chemoradiotherapy durvalumab consolidation therapy. However, moderate symptomatic pneumonitis (Grade 2) constitutes a significant adverse event that frequently leads to treatment interruption and warrants careful consideration of re-administration. We evaluated the efficacy and safety of durvalumab re-administration after recovery from grade 2 pneumonitis.

Methods

This retrospective study included 208 patients with LA-NSCLC who received post-chemoradiotherapy durvalumab consolidation therapy at seven institutions between July 2018 and March 2022. Among them, 62 developed Grade 2 pneumonitis that led to treatment interruption and were stratified into the durvalumab re-administration (n = 33) and durvalumab non-re-administration (n = 29) groups. Survival outcomes were analyzed using the Cox proportional hazards model.

Results

Participants in the durvalumab re-administration group had significantly longer progression-free survival (PFS; 32.0 months [95 % confidence interval (CI): 11.7–Not Available (NA)] vs. 5.3 months [95 % CI: 3.5–17.4], P = 0.003) and overall survival (OS; not reached [95 % CI: 29.0–NA] vs. 27.1 months [95 % CI: 12.1–NA], P = 0.012) than in the durvalumab non-re-administration group. Pneumonitis recurred in 30.3 % of the re-administration group, albeit without Grade ≥ 3 events. Multivariate analysis identified durvalumab re-administration as an independent predictor of improved survival, with hazard ratios of 0.31 (95 % CI: 0.15–0.65, P = 0.002) for PFS and 0.33 (95 % CI: 0.13–0.82, P = 0.017) for OS.

Conclusion

Durvalumab re-administration after grade 2 pneumonitis was associated with prolonged survival and a low recurrence rate of mild pneumonitis, which suggests that re-administration is a feasible, effective strategy with adequate monitoring.