Outcomes in biomarker-selected subgroups from the KESTREL study of durvalumab and tremelimumab in recurrent or metastatic head and neck squamous cell carcinoma.
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Embargo End Date
ICR Authors
Authors
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
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
Document Type
Journal Article
Date
2024-03-02
Date Accepted
2024-01-26
Abstract
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.
Citation
Cancer Immunology, Immunotherapy, 2024, 73 (4), pp. 70 -
Source Title
Cancer Immunology, Immunotherapy
Publisher
SPRINGER
ISSN
0340-7004
eISSN
1432-0851
1432-0851
1432-0851
Collections
Research Team
Targeted Therapy