PMID- 26025965 OWN - NLM STAT- MEDLINE DCOM- 20160405 LR - 20220317 IS - 1569-8041 (Electronic) IS - 0923-7534 (Print) IS - 0923-7534 (Linking) VI - 26 IP - 7 DP - 2015 Jul TI - Phase II trial of everolimus and erlotinib in patients with platinum-resistant recurrent and/or metastatic head and neck squamous cell carcinoma. PG - 1476-80 LID - 10.1093/annonc/mdv194 [doi] AB - BACKGROUND: Enhanced phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway is one of the key adaptive changes accounting for epidermal growth factor receptor (EGFR) inhibitor-resistant growth in head and neck squamous cell carcinoma (HNSCC). We designed a phase II clinical trial of EGFR tyrosine kinase inhibitor (TKI), erlotinib, in association with the mTOR inhibitor, everolimus, based on the hypothesis that the downstream effects of Akt through inhibition of mTOR may enhance the effectiveness of the EGFR-TKI in patients with recurrent/metastatic HNSCC. PATIENTS AND METHODS: Patients with histologically or cytologically confirmed platinum-resistant HNSCC received everolimus 5 mg and erlotinib 150 mg daily orally until disease progression, intolerable toxicity, investigator or patient decision. Cytokines and angiogenic factors profile, limited mutation analysis and p16 immunohistochemistry status were included in the biomarker analysis. RESULTS: Of the 35 assessable patients, 3 (8%) achieved partial response at 4 weeks, 1 confirmed at 12 weeks; overall response rate at 12 weeks was 2.8%. Twenty-seven (77%) patients achieved disease stabilization at 4 weeks, 11 (31%) confirmed at 12 weeks. Twelve-week progression-free survival (PFS) was 49%, median PFS 11.9 weeks and median overall survival (OS) 10.25 months. High neutrophil gelatinase lipocalin (P = 0.01) and vascular endothelial growth factor (VEGF) (P = 0.04) plasma levels were significantly associated with worse OS. CONCLUSIONS: The combination of erlotinib and everolimus did not show significant benefit in unselected patients with platinum-resistant metastatic HNSCC despite a manageable toxicity profile. Markers of tumor invasion and hypoxia identify a group of patients with particularly poor prognosis. CLINICAL TRIAL NUMBER: NCT00942734. CI - (c) The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com. FAU - Massarelli, E AU - Massarelli E AD - Departments of Thoracic Head and Neck Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, USA. FAU - Lin, H AU - Lin H AD - Biostatistics, Diagnostic Radiology, The University of Texas M.D. Anderson Cancer Center, Houston, USA. FAU - Ginsberg, L E AU - Ginsberg LE AD - Translational Molecular Pathology, The University of Texas M.D. Anderson Cancer Center, Houston, USA. FAU - Tran, H T AU - Tran HT AD - Departments of Thoracic Head and Neck Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, USA. FAU - Lee, J J AU - Lee JJ AD - Biostatistics, Diagnostic Radiology, The University of Texas M.D. Anderson Cancer Center, Houston, USA. FAU - Canales, J R AU - Canales JR AD - Translational Molecular Pathology, The University of Texas M.D. Anderson Cancer Center, Houston, USA. FAU - Williams, M D AU - Williams MD AD - Pathology, The University of Texas M.D. Anderson Cancer Center, Houston, USA. FAU - Blumenschein, G R Jr AU - Blumenschein GR Jr AD - Departments of Thoracic Head and Neck Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, USA. FAU - Lu, C AU - Lu C AD - Departments of Thoracic Head and Neck Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, USA. FAU - Heymach, J V AU - Heymach JV AD - Departments of Thoracic Head and Neck Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, USA. FAU - Kies, M S AU - Kies MS AD - Departments of Thoracic Head and Neck Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, USA. FAU - Papadimitrakopoulou, V AU - Papadimitrakopoulou V AD - Departments of Thoracic Head and Neck Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, USA vpapadim@mdanderson.org. LA - eng SI - ClinicalTrials.gov/NCT00942734 PT - Clinical Trial, Phase II PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20150529 PL - England TA - Ann Oncol JT - Annals of oncology : official journal of the European Society for Medical Oncology JID - 9007735 RN - 49DFR088MY (Platinum) RN - 9HW64Q8G6G (Everolimus) RN - DA87705X9K (Erlotinib Hydrochloride) SB - IM MH - Administration, Oral MH - Antineoplastic Combined Chemotherapy Protocols/*therapeutic use MH - Carcinoma, Squamous Cell/*drug therapy/mortality/secondary MH - Drug Resistance, Neoplasm/*drug effects MH - Erlotinib Hydrochloride/administration & dosage MH - Everolimus/administration & dosage MH - Female MH - Follow-Up Studies MH - Head and Neck Neoplasms/*drug therapy/mortality/pathology MH - Humans MH - Male MH - Neoplasm Recurrence, Local/*drug therapy/mortality/pathology MH - Neoplasm Staging MH - Platinum/administration & dosage MH - Prognosis MH - *Salvage Therapy MH - Survival Rate PMC - PMC4855241 OTO - NOTNLM OT - EGFR inhibitors OT - HNSCC OT - erlotinib OT - everolimus OT - mTOR inhibitors EDAT- 2015/05/31 06:00 MHDA- 2016/04/06 06:00 PMCR- 2016/07/01 CRDT- 2015/05/31 06:00 PHST- 2014/11/11 00:00 [received] PHST- 2015/04/14 00:00 [accepted] PHST- 2015/05/31 06:00 [entrez] PHST- 2015/05/31 06:00 [pubmed] PHST- 2016/04/06 06:00 [medline] PHST- 2016/07/01 00:00 [pmc-release] AID - S0923-7534(19)34510-7 [pii] AID - mdv194 [pii] AID - 10.1093/annonc/mdv194 [doi] PST - ppublish SO - Ann Oncol. 2015 Jul;26(7):1476-80. doi: 10.1093/annonc/mdv194. Epub 2015 May 29.