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.
Date
2023-03-01ICR Author
Author
Psyrri, A
Fayette, J
Harrington, K
Gillison, M
Ahn, M-J
Takahashi, S
Weiss, J
Machiels, J-P
Baxi, S
Vasilyev, A
Karpenko, A
Dvorkin, M
Hsieh, C-Y
Thungappa, SC
Segura, PP
Vynnychenko, I
Haddad, R
Kasper, S
Mauz, P-S
Baker, V
He, P
Evans, B
Wildsmith, S
Olsson, RF
Yovine, A
Kurland, JF
Morsli, N
Seiwert, TY
KESTREL Investigators,
Type
Journal Article
Metadata
Show full item recordAbstract
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.
Collections
Subject
durvalumab
head and neck squamous cell carcinoma
immune checkpoint inhibition
phase III study
programmed death-ligand 1
tremelimumab
Humans
Squamous Cell Carcinoma of Head and Neck
B7-H1 Antigen
Antineoplastic Combined Chemotherapy Protocols
Neoplasm Recurrence, Local
Carcinoma, Squamous Cell
Head and Neck Neoplasms
Research team
Targeted Therapy
Language
eng
Date accepted
2022-12-13
License start date
2023-03-01
Citation
Annals of Oncology, 2023, 34 (3), pp. 262 - 274
Publisher
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