Effects of serotonergic drugs on immune checkpoint inhibitor response: a pooled analysis of individual patient data from four Canadian Cancer Trials Group (CCTG) trials

Background Immune checkpoint inhibitors (ICIs) are used to treat various cancers. Serotonin receptors are expressed by immune cells. In preclinical models, serotonergic drugs affect T-cell cytokine production, proliferation and apoptosis. Interactions between clinical serotonergic drug use and dual ICI treatment remain unknown.Methods Individual patient data were pooled from 4 Canadian Cancer Trials Group (CCTG) trials of patients treated with dual ICI ± chemotherapy (n = 684). Serotonergic drug use was correlated with clinicopathologic characteristics, best overall response (BOR)/iBOR per RECIST 1.1/iRECIST, progression-free survival (PFS)/iPFS, overall survival (OS) and immune-related adverse events (irAEs) using Cochran – Mantel – Haenszel and log-rank tests.Results Eighty-three (12%) patients used serotonergic drugs at baseline and 118 (17%) at any time on trial. By multivariate analysis, serotonergic drug use at baseline was significantly associated with decreased iBOR (p = 0.04), but not PFS (p = 0.21), iPFS (p = 0.28), OS (p = 0.30) or incidence of grade 1/2 or 3/4 irAE (p = 0.85 and 0.99 respectively). Results were not significantly different with serotonergic drug use at any time on trial.Conclusion Use of serotonergic drugs did not impact PFS or OS in patients treated with dual ICI ± chemotherapy. This study supports the safe use of serotonergic drugs in the context of dual ICI therapy.