The following is a summary of “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” published in the December 2022 issue of Clinical Cancer by Nathan et al.

Study the effects of the mTOR inhibitor everolimus as an adjuvant on progression-free survival (PFS) in patients with advanced-stage head and neck squamous cell carcinoma (HNSCC), and report on correlative biological parameters linked with disease management. Patients with stage IV HNSCC were included between December 2010 and March 2015 in a prospective, randomized, double-blind phase II trial. All patients were disease-free following decisive therapy. Adjuvant everolimus (10 mg, oral) or placebo was given to patients for up to a year. Whole exome sequencing and p16 immunohistochemistry (IHC) were used to detect human papillomavirus infection (HPV) infection. The risk ratios were calculated using a Cox proportional hazard model. 

Comparisons in survival were made using log-rank tests. Overall, PFS was the key measure of success. Overall survival (OS) and toxicity assessment were secondary endpoints and goals. About 52 individuals were randomly assigned to receive either a placebo (n=24) or everolimus (n=28) [median (range) age, 58 (37-76) years; 43 men (83%), 9 women (17%)]. Everolimus had a marginally favorable effect on PFS (log-rank P=0.093; HR = 0.44; 95% CI, 0.17-1.17). P=0.29; HR= 0.57; 95% CI, 0.20-16.2), and OS was not different. 

Subgroup analysis revealed no change for p16-positive patients (n=21; P=0.93), but everolimus resulted in a substantial improvement in PFS for p16-negative patients (n=31; P=0.031; HR= 0.26; 95% CI, 0.07-0.97). Furthermore, compared to patients treated with placebo, TP53-mutated (TP53mut) patients treated with everolimus had a significantly longer PFS (log-rank P=0.027; HR=0.24; 95% CI, 0.06-0.95). Patients whose tumors were TP53 wild-type did not benefit from any different treatment (P=0.79). Patients with TP53 mutations or a lack of p16 are candidates for everolimus as a form of adjuvant therapy.