Multicenter study of first cycle toxicity and survival in patients with rare cancers treated with immune checkpoint inhibitors

The multicenter basket trial NCT02834013 in the USA included 684 patients receiving nivolumab and ipilimumab for rare cancers. Grade 1 or 2 treatment-related immune-related adverse events (irAEs) in the first cycle of therapy, compared to no irAE, were associated with longer overall survival (HR 0.61; p<0.001), whereas grade 3 or 4 irAEs in the first cycle of therapy, compared to no irAE, were associated with shorter OS (1.41; p=0.025). Similar, but weaker, associations were observed with progression-free survival and grade 1 or 2 irAEs (HR 0.83; p=0.067) and grade 3 or 4 irAEs (1.35; p=0.037) compared with no treatment irAEs in the first cycle. Grade 1 or 2 dermatologic toxicity was associated with improved OS compared to other grade 1 or 2 toxicities (HR 0.67; p=0.002). The authors conclude that in this large cohort of patients with rare tumors receiving immune checkpoint inhibitors, grade or irAE in the first cycle was predictive for survival.