Outcomes in biomarker-selected subgroups from the KESTREL study of durvalumab and tremelimumab in recurrent or metastatic head and neck squamous cell carcinoma Journal Article
| Authors: | Seiwert, T. Y.; 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.; Walker, J.; Real, K.; L’Hernault, A.; Psyrri, A. |
| Article Title: | Outcomes in biomarker-selected subgroups from the KESTREL study of durvalumab and tremelimumab in recurrent or metastatic head and neck squamous cell carcinoma |
| 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. © The Author(s) 2024. |
| Keywords: | adult; controlled study; human tissue; protein expression; treatment outcome; aged; human cell; major clinical study; overall survival; cancer recurrence; cisplatin; fluorouracil; drug efficacy; monotherapy; biomarkers; metabolism; carboplatin; ticilimumab; multiple cycle treatment; randomized controlled trial; cetuximab; tumor marker; monoclonal antibody; antibodies, monoclonal; immunotherapy; blood sampling; head and neck neoplasms; multicenter study; phase 3 clinical trial; head and neck tumor; programmed death 1 ligand 1; programmed death 1 receptor; head and neck squamous cell carcinoma; clinical outcome; immune checkpoint inhibitor; antibodies, monoclonal, humanized; high throughput sequencing; absolute lymphocyte count; humans; human; male; female; article; circulating tumor dna; absolute neutrophil count; durvalumab; neutrophil lymphocyte ratio; immune checkpoint inhibitors; biomarkers, tumor; squamous cell carcinoma of head and neck; b7-h1 antigen; tumor mutational burden; programmed cell death-1 receptor; metastatic head and neck cancer |
| Journal Title: | Cancer Immunology, Immunotherapy |
| Volume: | 73 |
| Issue: | 4 |
| ISSN: | 0340-7004 |
| Publisher: | Springer |
| Date Published: | 2024-03-02 |
| Start Page: | 70 |
| Language: | English |
| DOI: | 10.1007/s00262-024-03643-3 |
| PUBMED: | 38430375 |
| PROVIDER: | scopus |
| PMCID: | PMC10908636 |
| DOI/URL: | |
| Notes: | Article -- Source: Scopus |
