1. 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.
- Author
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Nathan, Cherie-Ann O, Hayes, D Neil, Karrison, Theodore, Harismendy, Olivier, Flores, José M, Moore-Medlin, Tara, Vokes, Everett E, Gutkind, J Silvio, Neupane, Prakash, Mills, Glenn, Sargi, Zoukaa, Seiwert, Tanguy, Grilley-Olson, Juneko, Day, Terry, Gillison, Maura, Wade, James L, Feldman, Lawrence, Jha, Gautam, Kozloff, Mark, O'Leary, Miriam, Worden, Francis P, and Cohen, Ezra EW
- Subjects
Biomedical and Clinical Sciences ,Clinical Sciences ,Oncology and Carcinogenesis ,Infectious Diseases ,Clinical Research ,Human Genome ,Genetics ,Clinical Trials and Supportive Activities ,Dental/Oral and Craniofacial Disease ,Cancer ,Rare Diseases ,6.1 Pharmaceuticals ,Male ,Humans ,Female ,Middle Aged ,Everolimus ,Squamous Cell Carcinoma of Head and Neck ,Prospective Studies ,Carcinoma ,Squamous Cell ,Head and Neck Neoplasms ,Epithelial Cells ,Oncology & Carcinogenesis ,Clinical sciences ,Oncology and carcinogenesis - Abstract
PurposeInvestigate 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.Patients and methodsThis 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.Results52 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).Conclusionsp16-negative and TP53mut patients may benefit from adjuvant treatment with everolimus.
- Published
- 2022