Effects of cannabinoids on immune checkpoint inhibitor response: CCTG pooled analysis of individual patient data
Creators: name: Coschi, Courtney H.
name: Ding, Keyue
name: Tong, Justin
name: Tu, Dongsheng
name: O’Callaghan, Christopher
name: Leighl, Natasha B.
name: Vera-Badillo, Francisco
name: Juergens, Rosalyn A.
name: Hao, Desiree
name: Seymour, Lesley
name: Renouf, Daniel J.
name: Chen, Eric
name: Gaudreau, Pierre-Olivier
name: Fung, Andrea S.
Publisher: name: Taylor & Francis
Year: 2025
Subjects: subject: Medicine
subject: Pharmacology
subject: Immunology
subject: FOS: Clinical medicine
subject: Cancer
subject: Mental Health

description: 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. Individual patient data from 4 Canadian Cancer Trials Group (CCTG) trials of patients treated with dual ICI ± chemotherapy (<i>n</i> = 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). 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 (<i>p</i> = 0.15), PFS (<i>p</i> = 0.12), OS (<i>p</i> = 0.35) or incidence of grade 1/2 or 3/4 irAEs (<i>p</i> = 0.96 and 0.65 respectively). Results were not significantly different with cannabinoid use at any time on trial. 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. Immune checkpoint inhibitors (ICI) have become an important treatment option for cancer patients and has been associated with improved survival outcomes across various tumor types. Cannabinoids are active components of cannabis and include tetrahydrocannabinol (THC) and cannabidiol (CBD). Cannabis use has increased in Canadian cancer patients and is often used for symptom management. Some studies have suggested that cannabinoids can alter the function of the immune system, which could impact the effectiveness of immune checkpoint inhibitors. Therefore, we aimed to evaluate whether cannabinoid use might impact the effectiveness of combination ICI treatment with durvalumab plus tremelimumab (with/without chemotherapy) using data from four clinical trials completed through the Canadian Cancer Trials Group (CCTG). We found no significant difference in response, survival outcomes or adverse events in patients who used cannabinoids with combination ICI treatment compared to cannabinoid non-users. This study supports the safe use of cannabinoids in the context of combination ICI therapy.