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

Autor: Sophie Wildsmith, Weimin Li, Song Wu, Ross Stewart, Nassim Morsli, Rajiv Raja, Qu Zhang, Jiabu Ye, Philip He, Jagdish Shetty, Alejandro Yovine, Nicholas Holoweckyj, Katia Real, Jill Walker, Magdalena Wrona, Melissa de los Reyes, Craig Barker, Jessica Whiteley, Robert Haddad, Lisa Licitra, Robert Ferris, Jérôme Fayette, Dan P. Zandberg, Lillian L. Siu, Ricard Mesía
Rok vydání: 2023
Předmět:
Zdroj: Clinical Cancer Research. 29:2066-2074
ISSN: 1557-3265
1078-0432
Popis: Purpose: Biomarkers that predict response to immune checkpoint inhibitors (ICI) 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 II HAWK and CONDOR and phase III EAGLE studies of durvalumab with or without tremelimumab in platinum-resistant R/M HNSCC. Patients and Methods: 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 blood 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 [HR, 0.52 (95% confidence interval, 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. Conclusions: 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.
Databáze: OpenAIRE
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