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 ( = 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 ( = 0.04), but not PFS ( = 0.21), iPFS ( = 0.28), OS ( = 0.30) or incidence of grade 1/2 or 3/4 irAE ( = 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.