Immunotherapy · 2025
Effects of cannabinoids on immune checkpoint inhibitor response: CCTG pooled analysis of individual patient data.
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Coschi Courtney H, Ding Keyue, Tong Justin, Tu Dongsheng, O'Callaghan Christopher, Leighl Natasha B, Vera-Badillo Francisco, Juergens Rosalyn A, Hao Desiree, Seymour Lesley, Renouf Daniel J, Chen Eric, Gaudreau Pierre-Olivier, Fung Andrea S
Аннотация
BACKGROUND: Immune checkpoint inhibitors (ICIs) benefit patients across various tumor types. ICIs block cancer and T-cell interactions whereas cannabinoids may inhibit T-cell activation, reducing lysis of tumor cells. Interactions between cannabinoid use and dual ICI treatment remain unknown.
METHODS: Individual patient data from 4 Canadian Cancer Trials Group (CCTG) trials of patients treated with dual ICI ± chemotherapy (n = 684) were pooled. Cochran - Mantel - Haenszel and log-rank tests (stratified by trial/treatment arms) correlated cannabinoid use 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).
RESULTS: Sixty-five (9.5%) patients took cannabinoids at any time on trial, 32 (4.7%) of which were using cannabinoids at baseline. By multivariate analysis, cannabinoid use at baseline was significantly associated with improved iPFS (0.05), but not iBOR (p = 0.15), PFS (p = 0.12), OS (p = 0.35) or incidence of grade 1/2 or 3/4 irAEs (p = 0.96 and 0.65 respectively). Results were not significantly different with cannabinoid use at any time on trial.
CONCLUSION: Improved iPFS with cannabinoid use in patients treated with durvalumab plus tremelimumab ± chemotherapy did not translate into OS benefits. This study supports the safe use of cannabinoids in the context of combination ICI therapy.
METHODS: Individual patient data from 4 Canadian Cancer Trials Group (CCTG) trials of patients treated with dual ICI ± chemotherapy (n = 684) were pooled. Cochran - Mantel - Haenszel and log-rank tests (stratified by trial/treatment arms) correlated cannabinoid use 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).
RESULTS: Sixty-five (9.5%) patients took cannabinoids at any time on trial, 32 (4.7%) of which were using cannabinoids at baseline. By multivariate analysis, cannabinoid use at baseline was significantly associated with improved iPFS (0.05), but not iBOR (p = 0.15), PFS (p = 0.12), OS (p = 0.35) or incidence of grade 1/2 or 3/4 irAEs (p = 0.96 and 0.65 respectively). Results were not significantly different with cannabinoid use at any time on trial.
CONCLUSION: Improved iPFS with cannabinoid use in patients treated with durvalumab plus tremelimumab ± chemotherapy did not translate into OS benefits. This study supports the safe use of cannabinoids in the context of combination ICI therapy.