Durvalumab with or without tremelimumab versus the EXTREME regimen as first-line treatment for recurrent or metastatic squamous cell carcinoma of the head and neck: KESTREL, a randomized, open-label, phase III study.

Abstract

BACKGROUND:

Patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) have a poor prognosis. The phase III KESTREL study evaluated the efficacy of durvalumab [programmed death-ligand 1 (PD-L1) antibody] with or without tremelimumab [cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) antibody], versus the EXTREME regimen in patients with R/M HNSCC.

PATIENTS AND METHODS:

Patients with HNSCC who had not received prior systemic treatment for R/M disease were randomized (2 : 1 : 1) to receive durvalumab 1500 mg every 4 weeks (Q4W) plus tremelimumab 75 mg Q4W (up to four doses), durvalumab monotherapy 1500 mg Q4W, or the EXTREME regimen (platinum, 5-fluorouracil, and cetuximab) until disease progression. Durvalumab efficacy, with or without tremelimumab, versus the EXTREME regimen in patients with PD-L1-high tumors and in all randomized patients was assessed. Safety was also assessed.

RESULTS:

Durvalumab and durvalumab plus tremelimumab were not superior to EXTREME for overall survival (OS) in patients with PD-L1-high expression [median, 10.9 and 11.2 versus 10.9 months, respectively; hazard ratio (HR) = 0.96; 95% confidence interval (CI) 0.69-1.32; P = 0.787 and HR = 1.05; 95% CI 0.80-1.39, respectively]. Durvalumab and durvalumab plus tremelimumab prolonged duration of response versus EXTREME (49.3% and 48.1% versus 9.8% of patients remaining in response at 12 months), correlating with long-term OS for responding patients; however, median progression-free survival was longer with EXTREME (2.8 and 2.8 versus 5.4 months). Exploratory analyses suggested that subsequent immunotherapy use by 24.3% of patients in the EXTREME regimen arm contributed to the similar OS outcomes between arms. Grade 3/4 treatment-related adverse events (TRAEs) for durvalumab, durvalumab plus tremelimumab, and EXTREME were 8.9%, 19.1%, and 53.1%, respectively.

CONCLUSIONS:

In patients with PD-L1-high expression, OS was comparable between durvalumab and the EXTREME regimen. Durvalumab alone, and with tremelimumab, demonstrated durable responses and reduced TRAEs versus the EXTREME regimen in R/M HNSCC.

• Authors: A Psyrri, J Fayette, K Harrington, M Gillison, M-J Ahn, S Takahashi, J Weiss, J-P Machiels, S Baxi, A Vasilyev, A Karpenko, M Dvorkin, C-Y Hsieh, S C Thungappa, P P Segura, I Vynnychenko, R Haddad, S Kasper, P-S Mauz, V Baker, P He, B Evans, S Wildsmith, R F Olsson, A Yovine, J F Kurland, N Morsli, T Y Seiwert, KESTREL Investigators
• Journal: Annals of oncology : official journal of the European Society for Medical Oncology (Ann Oncol) Vol. 34 Issue 3 Pg. 262-274 (03 2023) ISSN: 1569-8041 [Electronic] England
• PMID: 36535565 (Publication Type: Randomized Controlled Trial, Clinical Trial, Phase III, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.

Chemical References

• durvalumab
• tremelimumab
• B7-H1 Antigen

Topics

• Humans
• Squamous Cell Carcinoma of Head and Neck (etiology)
• B7-H1 Antigen
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Neoplasm Recurrence, Local
• Carcinoma, Squamous Cell
• Head and Neck Neoplasms (etiology)