title: Phase II trial of everolimus in patients with previously treated recurrent or metastatic head and neck squamous cell carcinoma.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  Everolimus was not active as monotherapy in unselected patients with recurrent/metastatic HNSCC. © 2016 Wiley Periodicals, Inc. Head Neck 38: 1759-1764, 2016.
authors.affiliation: Department of Internal Medicine, Division of Hematology/Oncology, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Jessica L
authors.initials: JL
authors.lastname: Geiger
authors.affiliation: Department of Internal Medicine, Division of Hematology/Oncology, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Julie E
authors.initials: JE
authors.lastname: Bauman
authors.affiliation: Department of Internal Medicine, Division of Hematology/Oncology, Case Western University, Cleveland, Ohio.
authors.forename: Michael K
authors.initials: MK
authors.lastname: Gibson
authors.affiliation: Biostatistics Facility, University of Pittsburgh, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania.
authors.forename: William E
authors.initials: WE
authors.lastname: Gooding
authors.affiliation: Department of Medicine, Division of Hematology/Oncology, University of Texas Health Science Center at San Antonio, San Antonio, Texas.
authors.forename: Prakash
authors.initials: P
authors.lastname: Varadarajan
authors.affiliation: School of Medicine, University of Crete, Crete, Greece.
authors.forename: Athanasios
authors.initials: A
authors.lastname: Kotsakis
authors.affiliation: National Institute of Dental and Craniofacial Research, Bethesda, Maryland.
authors.forename: Daniel
authors.initials: D
authors.lastname: Martin
authors.affiliation: National Institute of Dental and Craniofacial Research, Bethesda, Maryland.
authors.forename: Jorge Silvio
authors.initials: JS
authors.lastname: Gutkind
authors.affiliation: Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Matthew L
authors.initials: ML
authors.lastname: Hedberg
authors.affiliation: Department of Otolaryngology, University of California San Francisco, San Francisco, California.
authors.forename: Jennifer R
authors.initials: JR
authors.lastname: Grandis
authors.affiliation: Department of Medicine, Division of Hematology/Oncology, University of Texas Health Science Center at San Antonio, San Antonio, Texas.|Department of Medical Oncology, Hygeia Hospital, Athens, Greece.
authors.forename: Athanassios
authors.initials: A
authors.lastname: Argiris
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D000068338:Everolimus / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000473:pathology; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D009367:Neoplasm Staging; D011379:Prognosis; D018570:Risk Assessment; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000068338:Everolimus
keywords: PIK3CA mutations; clinical trial; everolimus; head and neck squamous cell carcinoma (HNSCC); mammalian target of rapamycin (mTOR) inhibitors