Phase II trial of everolimus in patients with previously treated recurrent or metastatic head and neck squamous cell carcinoma

• Published in: Head & neck 2016-12, Vol.38 (12), p.1759-1764
• Main Authors: Geiger, Jessica L., Bauman, Julie E., Gibson, Michael K., Gooding, William E., Varadarajan, Prakash, Kotsakis, Athanasios, Martin, Daniel, Gutkind, Jorge Silvio, Hedberg, Matthew L., Grandis, Jennifer R., Argiris, Athanassios
• Format: Article
• Language: English
• Subjects: Aged; Aged, 80 and over; Carcinoma, Squamous Cell - drug therapy; Carcinoma, Squamous Cell - mortality; Carcinoma, Squamous Cell - pathology; clinical trial; Disease-Free Survival; Dose-Response Relationship, Drug; Drug Administration Schedule; everolimus; Everolimus - adverse effects; Everolimus - therapeutic use; Female; Head and Neck Neoplasms - drug therapy; Head and Neck Neoplasms - mortality; Head and Neck Neoplasms - pathology; head and neck squamous cell carcinoma (HNSCC); Humans; Kaplan-Meier Estimate; Male; mammalian target of rapamycin (mTOR) inhibitors; Maximum Tolerated Dose; Middle Aged; Neoplasm Invasiveness - pathology; Neoplasm Recurrence, Local - drug therapy; Neoplasm Recurrence, Local - mortality; Neoplasm Recurrence, Local - pathology; Neoplasm Staging; PIK3CA mutations; Prognosis; Risk Assessment; Survival Analysis; Treatment Outcome
• ISSN: 1043-3074; 1097-0347
• DOI: 10.1002/hed.24501

Background Patients with recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) demonstrate aberrant activation of the phosphotidylinositol‐3‐kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway. We examined the efficacy of everolimus, an mTOR inhibitor, in patients with recurrent or metastatic HNSCC. Methods This single‐arm phase II study enrolled biomarker‐unselected patients with recurrent or metastatic HNSCC who failed at least 1 prior therapy. Everolimus was administered until progressive disease or unacceptable toxicity. Primary endpoint was clinical benefit rate (CBR). Secondary endpoints included progression‐free survival (PFS), overall survival (OS), and evaluation of tissue and serum biomarkers related to the PIK3CA pathway. Results Seven of 9 patients treated in the first stage were evaluable. No objective responses were seen; CBR was 28%. Three patients discontinued everolimus because of toxicity. Median PFS and OS were 1.5 and 4.5 months, respectively. No activating PI3K mutations were identified in available tumor tissue. Conclusion Everolimus was not active as monotherapy in unselected patients with recurrent/metastatic HNSCC. © 2016 Wiley Periodicals, Inc. Head Neck 38: 1759–1764, 2016