A retrospective analysis of concomitant opioid usage with immunotherapy in recurrent/metastatic head and neck squamous cell carcinoma.

Abstract

e18103 Background: Cancer-related pain is a significant consequence of disease for recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) patients. Pain severity contributes to a high opioid burden for this patient population. Recent studies have shown that opioids are immunosuppressive, diminishing the efficacy of immunotherapy (IO), which is the standard of care for R/M HNSCC. The prognostic impact of the concomitant use of opioids in R/M HNSCC patients receiving IO remains unclear. In this study, we aimed to analyze whether the use of opioids along with IO in patients with R/M HNSCC impacts clinical outcomes. Methods: This was a retrospective, IRB-approved study that examined R/M HNSCC patients at a single NCI-designated comprehensive cancer center treated with IO from 2022–2025. Patients were divided into two groups: those who used opioids while on first-line IO (Opioids) and those that did not (Controls). Descriptive variables including demographic and clinical characteristics (age, gender, race/ethnicity, histology, metastatic sites, PD-L1 and HPV status), IO treatment (type, therapy duration, use of other biologic treatment), and opioid usage (type, dose in morphine milligram equivalency [MME], therapy duration) were collected. Primary outcome was overall survival (OS) from time of start of IO therapy to death or date of last follow up. Statistical analysis was descriptive and OS was analyzed using GraphPad Prism v 10 and the Gehan-Breslow-Wilcoxon test. Results: Among 45 R/M HNSCC patients, 24 were treated with first-line IO without opioid use (Controls) and 21 were treated with opioids and IO concurrently (Opioids). Median age at diagnosis of R/M disease was 65 (Opioids 63; Controls 66). Gender and race/ethnicity were consistent across groups and most commonly Non-Hispanic White (N=21, 35%) and male (N=35, 58.3%). Most patients had ECOG performance status (PS) of 0 (N=16, 36%) or 1 (N=19, 42%). Oral cavity (49%) and oropharyngeal (29%) were the most prevalent primary sites; 56% of the oropharyngeal group were p16 positive. 28 patients had a known PD-L1 combined positive score (CPS) ≥ 1. Patients were treated with single-agent IO (N=23, 51%) or with another therapy (plus chemotherapy N=21, 47%; plus biologic N=1, 2%). Pembrolizumab (N=35, 78%) and nivolumab (N=8, 18%) were the most common IO. Median time on IO was 133 days for Controls and 120 days for Opioids. The Opioids group had a median total MME per patient of 5499 (range 30-59130; median dosage of 45 MME/day). Median OS (months) was statistically significantly different between both groups (Opioids 9.3; Controls 27.1; p=0.04). Conclusions: This study showed a significant difference in survival in R/M HNSCC patients taking opioids with IO compared to patients not exposed to opioids. Further investigation is needed to understand the potential effects conferred by opioid use in R/M HNSCC patients on IO.