American Association for Cancer Research
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Supplementary Table S3 from 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

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posted on 2023-04-01, 00:06 authored by Cherie-Ann O. Nathan, D. Neil Hayes, Theodore Karrison, Olivier Harismendy, José M. Flores, Tara Moore-Medlin, Everett E. Vokes, J. Silvio Gutkind, Prakash Neupane, Glenn Mills, Zoukaa Sargi, Tanguy Seiwert, Juneko Grilley-Olson, Terry Day, Maura Gillison, James L. Wade, Lawrence Feldman, Gautam Jha, Mark Kozloff, Miriam O'Leary, Francis P. Worden, Ezra E.W. Cohen

Adverse events at least possibly related to study drug by NIH-NCI Common Terminology Criteria for Adverse Events (CTCAE), version. 4.0.


Comprehensive Cancer Center, University of Chicago Medical Center (Comprehensive Cancer Center)

National Cancer Institute (NCI)

United States Department of Health and Human Services

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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.

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