Association of Immune-Related Adverse Events With Efficacy in Consolidation Nivolumab Plus Ipilimumab or Nivolumab Alone After Chemoradiation in Patients With Unresectable Stage III Nonsmall Cell Lung Cancer: An Exploratory Analysis From the Big 10 Cancer Research Consortium Study BTCRC LUN 16-081.

Background: Immunotherapy has been widely incorporated into the treatment of patients with non-small-cell lung cancer (NSCLC). Many of these patients will experience immune-related adverse events (irAEs) without decreased efficacy. 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 nivolumab (N) plus ipilimumab (IPI) vs N alone following chemoradiotherapy in unresectable Stage IIIA/IIIB NSCLC.

Results: A total of 105 patients enrolled from 9/2017 to 4/2021. In arm A (N alone), 65 % of patients developed irAEs with no difference in PFS or OS in patients with and without irAEs. In arm B (IPI+N), 84 % of patients developed irAE with no difference in OS in patients with and without irAEs, but longer PFS in those who experienced irAEs (30.9 vs. 6.8mo, P = .010). Patients in Arm A that discontinued treatment due to irAE (n = 8) had shorter PFS (8.2 vs. 31.9mo, P ≤ .0001) and OS (12.3mo vs. NE, P < .0001). Patients in Arm B that discontinued treatment due to irAEs (n = 18) had no difference in either PFS or OS.

Conclusions: The development of irAEs after chemoradiotherapy due to the use of Nivolumab alone or in combination with Ipilimumab did not result in reduced efficacy outcomes, with an observed improvement in PFS in the combination arm. If the irAEs resulted in discontinuation of treatment, this was associated with decreased efficacy outcomes in the N alone arm but not in the IPI + N arm.