Tumor Mutational Burden as a Predictor of Survival With Durvalumab and/or Tremelimumab Treatment in Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma.

PURPOSE Biomarkers that predict response to immune checkpoint inhibitors (ICIs) in recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) are needed. This retrospective study assessed tumor mutational burden (TMB) and outcomes in the phase 2 HAWK and CONDOR and phase 3 EAGLE studies of durvalumab with or without tremelimumab in platinum-resistant R/M HNSCC. EXPERIMENTAL DESIGN Tumor samples from HAWK/CONDOR (N=153) and blood samples from EAGLE (N=247) were analyzed for TMB. Associations with survival were evaluated for tissue TMB (tTMB) at cutoffs from 10 to 20 mutations/megabase (mut/Mb) and for plasma TMB (bTMB) at cutoffs from 8 to 24 mut/Mb. RESULTS In HAWK/CONDOR, overall survival (OS) with durvalumab with or without tremelimumab was longer for high versus low tTMB: statistically significant differences were observed with durvalumab plus tremelimumab at tTMB≥10 mut/Mb (hazard ratio [HR], 0.52 [95% CI, 0.28-0.98]) and tTMB≥12 mut/Mb (HR, 0.46 [95% CI, 0.24-0.86]). In EAGLE, a significant OS benefit versus chemotherapy was observed with durvalumab and durvalumab plus tremelimumab at bTMB≥16 mut/Mb (HR, 0.39 [95% CI, 0.20-0.76] and 0.38 [95% CI, 0.19-0.78], respectively) but not bTMB<16 mut/Mb (HR, 0.92 [0.61-1.37] and 0.92 [95% CI, 0.62-1.36], respectively). A significant progression-free survival benefit was also observed in the ICI arms versus chemotherapy at bTMB≥16 mut/Mb. CONCLUSION Findings support TMB as a biomarker for predicting survival in patients with platinum-resistant R/M HNSCC treated with ICIs. The analysis of EAGLE demonstrated that bTMB was predictive of survival with ICI treatment versus chemotherapy in a large, randomized controlled study population.