A Randomized Multi-institutional Phase II Trial of Everolimus as Adjuvant Therapy in Patients with Locally Advanced Squamous Cell Cancer of the Head and Neck.
Journal
Clinical cancer research : an official journal of the American Association for Cancer Research
ISSN: 1557-3265
Titre abrégé: Clin Cancer Res
Pays: United States
ID NLM: 9502500
Informations de publication
Date de publication:
01 12 2022
01 12 2022
Historique:
received:
02
12
2021
revised:
15
04
2022
accepted:
26
09
2022
pubmed:
5
10
2022
medline:
3
12
2022
entrez:
4
10
2022
Statut:
ppublish
Résumé
Investigate whether adjuvant everolimus, an mTOR inhibitor, improves progression-free survival (PFS) in advanced-stage head and neck squamous cell carcinoma (HNSCC) and provide outcomes related to correlative biological factors associated with disease control. This was a prospective, randomized, double-blind phase II trial of patients with advanced-stage HNSCC from 13 institutions who were confirmed disease-free post-definitive therapy and enrolled between December 2010 and March 2015. Patients received adjuvant everolimus or placebo daily (10 mg, oral) for a maximum of 1 year. p16 IHC as a surrogate marker for human papillomavirus infection and whole-exome sequencing were performed. Cox proportional hazard models estimated hazard rates. Log-rank tests evaluated differences in survival. The primary endpoint was PFS. Secondary endpoints and objectives included overall survival (OS) and toxicity assessment. 52 patients [median (range) age, 58 (37-76) years; 43 men (83%), 9 women (17%)] were randomized to placebo (n = 24) or everolimus (n = 28). PFS favored everolimus, but was not significant [log-rank P = 0.093; HR = 0.44; 95% confidence interval (CI), 0.17-1.17]. There was no difference in OS (P = 0.29; HR = 0.57; 95% CI, 0.20-16.2). Everolimus resulted in significant improvement in PFS for p16-negative patients (n = 31; P = 0.031; HR = 0.26; 95% CI, 0.07-0.97), although subgroup analysis showed no difference for p16-positive patients (n = 21; P = 0.93). Further, PFS was significantly higher in TP53-mutated (TP53mut) patients treated with everolimus compared with placebo (log-rank P = 0.027; HR = 0.24; 95% CI, 0.06-0.95). No treatment difference was seen in patients with TP53 wild-type tumors (P = 0.79). p16-negative and TP53mut patients may benefit from adjuvant treatment with everolimus.
Identifiants
pubmed: 36194164
pii: 709543
doi: 10.1158/1078-0432.CCR-21-4290
pmc: PMC9722644
mid: NIHMS1840796
doi:
Substances chimiques
Everolimus
9HW64Q8G6G
Banques de données
ClinicalTrials.gov
['NCT01111058']
Types de publication
Randomized Controlled Trial
Clinical Trial, Phase II
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
5040-5048Subventions
Organisme : NCI NIH HHS
ID : R01 CA102363
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA247551
Pays : United States
Organisme : NIDCR NIH HHS
ID : R01 DE026870
Pays : United States
Organisme : NCI NIH HHS
ID : UG1 CA233333
Pays : United States
Informations de copyright
©2022 American Association for Cancer Research.
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