Jessica L Geiger1, Julie E Bauman1, Michael K Gibson2, William E Gooding3, Prakash Varadarajan4, Athanasios Kotsakis5, Daniel Martin6, Jorge Silvio Gutkind6, Matthew L Hedberg7, Jennifer R Grandis8, Athanassios Argiris4,9. 1. Department of Internal Medicine, Division of Hematology/Oncology, University of Pittsburgh, Pittsburgh, Pennsylvania. 2. Department of Internal Medicine, Division of Hematology/Oncology, Case Western University, Cleveland, Ohio. 3. Biostatistics Facility, University of Pittsburgh, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania. 4. Department of Medicine, Division of Hematology/Oncology, University of Texas Health Science Center at San Antonio, San Antonio, Texas. 5. School of Medicine, University of Crete, Crete, Greece. 6. National Institute of Dental and Craniofacial Research, Bethesda, Maryland. 7. Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, Pennsylvania. 8. Department of Otolaryngology, University of California San Francisco, San Francisco, California. 9. Department of Medical Oncology, Hygeia Hospital, Athens, Greece.
Abstract
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.
RCT Entities:
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.
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