Association Between the Early Discontinuation of Durvalumab and Poor Survival in Patients With Stage III NSCLC

Abstract

Introduction: Durvalumab after concurrent chemoradiation (cCRT) has been found to improve outcomes of patients with unresected stage III NSCLC. However, the survival impact of discontinuing durvalumab early owing to adverse events (AEs) remains unknown. Methods: Patients with stage III NSLCC treated with cCRT and greater than or equal to one dose of durvalumab across a multisite cancer center were evaluated. The median durvalumab treatment duration among patients who discontinued owing to AEs (2.1 mo) defined two patient cohorts: early discontinuation (<2.1 mo) and late discontinuation. Progression-free survival (PFS) and overall survival were assessed. Results: In total, 113 patients treated with cCRT and a median of 8.5 months of durvalumab were assessed, of which 30 (26%) discontinued durvalumab owing to AEs after a median of 2.1 months of treatment. Patients in the early- and late-discontinuation cohorts were treated with a median of 0.9 and 4.3 months of durvalumab, respectively. The median PFS among patients who did not discontinue durvalumab owing to AEs was 29.5 months. Among patients that discontinued durvalumab owing to AEs, overall survival and PFS were inferior in the early- versus late-discontinuation cohort (median PFS = 10.7 versus 32.9 mo, p < 0.001) and durvalumab treatment duration associated with PFS on multivariate analysis (hazard ratio = 0.52 [95% confidence interval: 0.31–0.88], p = 0.014). Conclusions: We found that the duration of durvalumab treatment among patients who discontinued therapy owing to AEs impacts survival. However, patients treated with approximately 4 months of durvalumab maintained outcomes as compared with patients who did not discontinue therapy owing to AEs. Durvalumab rechallenge should be considered in patients with less than 2 months of therapy.

Keywords

• Durvalumab
• Stage III NSCLC
• Chemoradiation
• Pneumonitis
• Toxicity