dc.contributor.author | Psyrri, A | |
dc.contributor.author | Fayette, J | |
dc.contributor.author | Harrington, K | |
dc.contributor.author | Gillison, M | |
dc.contributor.author | Ahn, M-J | |
dc.contributor.author | Takahashi, S | |
dc.contributor.author | Weiss, J | |
dc.contributor.author | Machiels, J-P | |
dc.contributor.author | Baxi, S | |
dc.contributor.author | Vasilyev, A | |
dc.contributor.author | Karpenko, A | |
dc.contributor.author | Dvorkin, M | |
dc.contributor.author | Hsieh, C-Y | |
dc.contributor.author | Thungappa, SC | |
dc.contributor.author | Segura, PP | |
dc.contributor.author | Vynnychenko, I | |
dc.contributor.author | Haddad, R | |
dc.contributor.author | Kasper, S | |
dc.contributor.author | Mauz, P-S | |
dc.contributor.author | Baker, V | |
dc.contributor.author | He, P | |
dc.contributor.author | Evans, B | |
dc.contributor.author | Wildsmith, S | |
dc.contributor.author | Olsson, RF | |
dc.contributor.author | Yovine, A | |
dc.contributor.author | Kurland, JF | |
dc.contributor.author | Morsli, N | |
dc.contributor.author | Seiwert, TY | |
dc.contributor.author | KESTREL Investigators, | |
dc.coverage.spatial | England | |
dc.date.accessioned | 2023-04-12T10:04:54Z | |
dc.date.available | 2023-04-12T10:04:54Z | |
dc.date.issued | 2023-03-01 | |
dc.identifier | S0923-7534(22)04778-0 | |
dc.identifier.citation | Annals of Oncology, 2023, 34 (3), pp. 262 - 274 | |
dc.identifier.issn | 0923-7534 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/5742 | |
dc.identifier.eissn | 1569-8041 | |
dc.identifier.eissn | 1569-8041 | |
dc.identifier.doi | 10.1016/j.annonc.2022.12.008 | |
dc.description.abstract | 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. | |
dc.format | Print-Electronic | |
dc.format.extent | 262 - 274 | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | ELSEVIER | |
dc.relation.ispartof | Annals of Oncology | |
dc.rights.uri | https://creativecommons.org/licenses/by-nc-nd/4.0/ | |
dc.subject | durvalumab | |
dc.subject | head and neck squamous cell carcinoma | |
dc.subject | immune checkpoint inhibition | |
dc.subject | phase III study | |
dc.subject | programmed death-ligand 1 | |
dc.subject | tremelimumab | |
dc.subject | Humans | |
dc.subject | Squamous Cell Carcinoma of Head and Neck | |
dc.subject | B7-H1 Antigen | |
dc.subject | Antineoplastic Combined Chemotherapy Protocols | |
dc.subject | Neoplasm Recurrence, Local | |
dc.subject | Carcinoma, Squamous Cell | |
dc.subject | Head and Neck Neoplasms | |
dc.title | 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. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2022-12-13 | |
dc.date.updated | 2023-04-12T10:04:27Z | |
rioxxterms.version | VoR | |
rioxxterms.versionofrecord | 10.1016/j.annonc.2022.12.008 | |
rioxxterms.licenseref.startdate | 2023-03-01 | |
rioxxterms.type | Journal Article/Review | |
pubs.author-url | https://www.ncbi.nlm.nih.gov/pubmed/36535565 | |
pubs.issue | 3 | |
pubs.organisational-group | /ICR | |
pubs.organisational-group | /ICR/Primary Group | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Cancer Biology | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Cancer Biology/Targeted Therapy | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Targeted Therapy | |
pubs.organisational-group | /ICR/ImmNet | |
pubs.publication-status | Published | |
pubs.publisher-url | http://dx.doi.org/10.1016/j.annonc.2022.12.008 | |
pubs.volume | 34 | |
icr.researchteam | Targeted Therapy | |
dc.contributor.icrauthor | Harrington, Kevin | |
icr.provenance | Deposited by Mr Arek Surman on 2023-04-12. Deposit type is initial. No. of files: 1. Files: 1-s2.0-S0923753422047780-main.pdf | |