Association of immune-related adverse events and efficacy outcomes in phase II trial of consolidation nivolumab plus ipilimumab or nivolumab alone after chemoradiation in patients with unresectable stage III non-small-cell lung cancer (NSCLC)

8565 Background: Immunotherapy has been widely incorporated into the treatment of patients with non-small-cell lung cancer. Many of these patients will experience immune-related adverse events (irAEs) that may lead to early discontinuation of therapy. Previous studies have reported that patients with Stage III and metastatic NSCLC who experienced irAEs receive fewer cycles of immunotherapy without decreased efficacy. Here we report a retrospective analysis of the association between irAEs and efficacy outcomes from the BTCRC LUN 16-081 randomized phase 2 trial of consolidation immunotherapy with nivolumab (N) plus ipilimumab (IPI) vs N alone following concurrent chemoradiotherapy in patients with unresectable Stage IIIA/IIIB NSCLC. Methods: A total of 105 eligible patients were enrolled from 9/2017 to 4/2021. Demographics, disease characteristics, and number of immunotherapy cycles received were reported in patients with and without irAEs in the two arms. Chi-square test was used for comparisons for categorical variables and Wilcoxon test for continuous variables. The Kaplan-Meier method was used to analyze progression-free survival (PFS) and overall survival (OS). A log-rank test was used to compare groups. Results: In treatment arm A (N alone), any grade irAEs occurred in 64.8% of patients. At a follow up of 48 months, there was no significant difference in number of N cycles started (6 vs 6, p = 0.238), progression free survival (29.4 vs 31.9 mo, p = 0.897), or overall survival (NE vs. 31.9 mo, p = 0.798) in patients with and without irAEs. Patients who discontinued N because of irAEs (n = 8 or 14.8% of patients) received significantly fewer cycles of N (2 vs 6, p = < .0001) and had a shorter PFS (8.2 vs. 31.9 months, p = < .0001) and OS (12.3 months vs. NE, p < .0001). In treatment arm B (IPI+N), any grade irAEs occurred in 84.3% of patients. At follow up of 48 months, there was no significant difference in number of IPI+N started (4 vs. 4, p = 0.260) or overall survival (NE vs. NE, p = 0.576), but there was a significantly longer PFS in those who experienced irAEs (30.9 months vs. 6.8 months, p = 0.0083). Patients who discontinued IPI+N because of irAEs (n = 18 or 35.3% of patients) received significantly fewer cycles of IPI+N (2 vs 4, p = < .0001) without a significant difference in PFS (28.1 vs. 25.3 mo, p = 0.830) or OS (NE vs NE, p = 0.755). Conclusions: The occurrence of irAEs alone in both arms, regardless of number, was not associated with decreased efficacy outcomes in this exploratory analysis. However, if irAEs resulted in the discontinuation of therapy, these patients did have a shorter PFS and OS in the N alone arm. This difference was not observed in the IPI+N arm and those who experienced any irAEs in the IPI+N arm had an improved PFS.