The effect of opioids on the efficacy of immunotherapy in recurrent/metastatic squamous cell carcinoma of the head and neck.

Head and neck squamous cell carcinoma (HNSCC) causes severe pain and opioids, the mainstay of pain management, may have immunomodulatory effects. We evaluated the effect of opioids on immunotherapy efficacy in recurrent/metastatic (R/M) HNSCC patients. In a retrospective study of 66 R/M HNSCC patients from 2015 to 2020, opioid dosage, calculated as mean morphine milligram equivalent per day, was assessed on the day of anti-PD-1 monoclonal antibody (mAb) treatment and most recent prior visit. Intratumoral T cells were evaluated by single cell RNAseq and immunohistochemistry prior to treatment. Univariable and multivariable Cox proportional hazards and logistic regression models were used to estimate the association between opioid usage, progression-free survival (PFS), overall survival (OS), disease control rate. Patients were 79% male, 35% oropharynx, 35% oral cavity, 40% locoregional recurrence, and 56% platinum failure. Higher opioid dosage by continuous variable was significantly associated with lower PFS (p = 0.016) and OS (p < 0.001). In multivariable analysis, including platinum failure status and PD-L1, higher opioids were associated with lower OS. Opioid usage by categorical variable was associated with significantly lower intratumoral CD8 In our study cohort of anti-PD-1 mAb treatment in R/M HNSCC patients, higher opioids were associated with significantly lower PFS and OS and lower CD8

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Déclaration de conflit d'intérêts

Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [RL Ferris consults for Aduro Biotech Inc., Bain Capital Life Sciences, Iovance Biotherapeutics Inc., Nanobiotix, Ono Pharmaceutical Co. Ltd., Torque Therapeutics Inc., and TTMS; is on the advisory board for Amgen, AstraZeneca/MedImmune, Bristol-Myers Squibb, EMB Serono, GlaxoSmithKline, Lilly, MacroGenics, Merck, Numab Therapeutics AG, Pfizer, PPD, Regeneron Pharmaceuticals Inc., and Tesaro; receives clinical trial support from AstraZeneca/MedImmune, Bristol-Myers Squibb, and Merck; and receives research funding from Astra-Zeneca/MedImmune, Bristol-Myers Squibb, Tesaro, TTMS, and VentiRx Pharmaceuticals. GM Delgoffe consults for and/or is on the scientific advisory board of BlueSphere Bio, Century Therapeutics, Novasenta, Pieris Pharmaceuticals and Western Oncolytics/Kalivir; has grants from bluebird bio, Novasenta, Pfizer, Pieris Pharmaceuticals, TCR2 and Western Oncolytics/Kalivir; and owns stock in Novasenta. DP Zandberg is on the advisory board of Blueprint Medicines and Prelude Therapeutics, consults for Macrogenics, and received institutional support for role as PI from Merck, BMS, AstraZeneca, GlaxoSmithKline, Aduro, Astellas, Macrogenics, Lilly, Bicara, Checkmate Pharma, and Novasenta. All other authors have nothing to disclose.].