Outcomes in Biomarker-Selected Subgroups From the KESTREL Study of Durvalumab and Tremelimumab in Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma

Authors

Tanguy Y Seiwert
Sophie Wildsmith
Jérôme Fayette
Kevin Harrington
Maura Gillison
Myung-Ju Ahn
Shunji Takahashi
Jared Weiss
Jean-Pascal Machiels
Shrujal Baxi
Valerie Baker
Brent Evans
Nassim Morsli
Jill Walker
Katia Real
Anne L'Hernault
Amanda Psyrri

Publication Date

3-2-2024

Journal

Cancer Immunology, Immunotherapy

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.

Keywords

Humans, Squamous Cell Carcinoma of Head and Neck, B7-H1 Antigen, Treatment Outcome, Head and Neck Neoplasms, Biomarkers, Tumor, Antibodies, Monoclonal, Antibodies, Monoclonal, Humanized

Comments

Supplementary Materials

PMID: 38430375