Impact of Tobacco, Marijuana, and Alcohol use on Overall Survival in Recurrent Metastatic head and neck Cancer Patients Treated with Immune Checkpoint Inhibitors

Background: The response rates to immune checkpoint inhibitors (ICI) remain low (13-20%) in metastatic head and neck cancer patients and better understanding of factors predictive of response to these agents is urgently needed. Here we explore the impact of smoking status, marijuana use and alcohol on treatment outcomes in recurrent-metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) treated with ICI. Methods: We performed a retrospective analysis of 201 R/M HNSCC patients treated with ICI between January 15th 2016 and April 9th 2020 at a single institution. Results: Gender: 154 male (77%), 47 female (23%). Median age 61 (IQR: 55-68). ICI drug: pembrolizumab 100 (50%), nivolumab 91 (45%), nivolumab+ipilimumab 10 (5%). Line of therapy: first: 98 (49%), second and beyond: 103 (51%). Tumor site: oropharynx 84 (42%), oral cavity 45 (22%), larynx 26 (13%), other sites 46 (23%). p16 tumor status: negative 132 (66%), positive 69 (34%). Smoking status: former 111 (55%), never 54 (27%), current 36 (18%), median pack-year 18 (IQR: 0-37). Alcohol use: yes 110 (55%), no 91 (54%). Marijuana use: yes 47 (23%), no 154 (77%). Overall response rate: 36 (18%). Median OS: 12 months (95% CI: 9.4-14.8). Tobacco: former (HR: 0.75, 95% CI: 0.50, 1.11), current (HR: 0.58, 95% CI: 0.33, 1.02). Marijuana: yes (HR: 0.93, 95% CI: 0.58, 1.49). Alcohol: yes (HR: 1.04, 95% CI: 0.72, 1.49). Conclusion: In our cohort, smoking status, marijuana use and alcohol consumption did not have a statistically significant impact on OS in patients with R/M HNSCC treated with ICI. Trial registration: retrospectively registered.