Outcomes in biomarker-selected subgroups from the KESTREL study of durvalumab and tremelimumab in recurrent or metastatic head and neck squamous cell carcinoma.
Date
2024-03-02ICR Author
Author
Seiwert, TY
Wildsmith, S
Fayette, J
Harrington, K
Gillison, M
Ahn, M-J
Takahashi, S
Weiss, J
Machiels, J-P
Baxi, S
Baker, V
Evans, B
Morsli, N
Jill Walker,
Real, K
L'Hernault, A
Psyrri, A
Type
Journal Article
Metadata
Show full item recordAbstract
BACKGROUND: Selective biomarkers may improve outcomes in patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) treated with immune checkpoint inhibitor therapy. We investigated three independent biomarkers for association with efficacy in the randomized, phase III KESTREL study (NCT02551159) of first-line durvalumab monotherapy or durvalumab plus tremelimumab versus the EXTREME regimen: programmed cell death ligand-1 (PD-L1) immunohistochemistry, blood tumor mutational burden (bTMB) via circulating tumor DNA, and neutrophil-to-lymphocyte ratio (NLR). METHODS: Tumor or blood samples from patients enrolled in the KESTREL study were analyzed for PD-L1, bTMB, and NLR. Associations with overall survival (OS) or objective response rates (ORRs) were evaluated based on prespecified cut-offs for PD-L1 (tumor cell [TC] ≥ 50%/immune cell ≥ 25% or TC ≥ 25%), bTMB (≥ 16 mutations [mut] per megabase [Mb]), and NLR (≤ 7). Ad hoc analyses of exploratory cut-offs were performed. RESULTS: Prespecified or exploratory cut-offs for PD-L1 did not enrich for ORR or OS for durvalumab monotherapy or durvalumab plus tremelimumab versus EXTREME. In the bTMB ≥ 16 mut/Mb subgroup, OS hazard ratios (95% confidence interval) for durvalumab monotherapy and durvalumab plus tremelimumab versus EXTREME were 0.90 (0.48-1.72) and 0.69 (0.39-1.25), respectively. Complete response rates were 8.6% with durvalumab plus tremelimumab and 4.3% with EXTREME (≥ 16 mut/Mb subgroup). No improvement in OS was observed for durvalumab monotherapy or durvalumab plus tremelimumab versus EXTREME at prespecified or exploratory NLR cut-offs. CONCLUSIONS: bTMB demonstrated potential utility for selecting patients with R/M HNSCC who benefited from durvalumab with or without tremelimumab versus EXTREME. Trial registration ClinicalTrials.gov identifier NCT02551159.
Collections
Subject
Biomarkers
Head and neck neoplasms
Immune checkpoint inhibitors
Immunotherapy
Programmed cell death-1 receptor
Humans
Squamous Cell Carcinoma of Head and Neck
B7-H1 Antigen
Treatment Outcome
Head and Neck Neoplasms
Biomarkers, Tumor
Antibodies, Monoclonal
Antibodies, Monoclonal, Humanized
Research team
Targeted Therapy
Language
eng
Date accepted
2024-01-26
License start date
2024-03-02
Citation
Cancer Immunology, Immunotherapy, 2024, 73 (4), pp. 70 -
Publisher
SPRINGER