Randomized phase II trial of cixutumumab alone or with cetuximab for refractory recurrent/metastatic head and neck squamous cell carcinoma
Autor: | Renata Ferrarotto, Ezra E.W. Cohen, Shanthi Marur, Bonnie S. Glisson, Jan Cosaert, Jennifer E. Tseng, Barbara A. Murphy, J. Jack Lee, William N. William, Nusrat Harun, Christopher Y. Thomas, Dong M. Shin, Richard Willey, Ignacio W. Wistuba, Robert I. Haddad |
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Rok vydání: | 2018 |
Předmět: |
0301 basic medicine
Oncology Male Cancer Research medicine.medical_specialty medicine.medical_treatment Cetuximab Antibodies Monoclonal Humanized 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Antineoplastic Agents Immunological Insulin-Like Growth Factor II Internal medicine Antineoplastic Combined Chemotherapy Protocols Clinical endpoint Biomarkers Tumor Medicine Humans Epidermal growth factor receptor Insulin-Like Growth Factor I Neoplasm Metastasis Aged Chemotherapy biology business.industry Squamous Cell Carcinoma of Head and Neck Cixutumumab medicine.disease Head and neck squamous-cell carcinoma ErbB Receptors Regimen 030104 developmental biology chemistry Head and Neck Neoplasms 030220 oncology & carcinogenesis biology.protein Biomarker (medicine) Female Oral Surgery Neoplasm Recurrence Local business medicine.drug |
Zdroj: | Oral oncology. 82 |
ISSN: | 1879-0593 |
Popis: | Objectives Cixutumumab (CIX) and cetuximab (CET) monoclonal antibodies block ligand-binding to insulin-like growth factor-1 receptor (IGF-1R) and epidermal growth factor receptor (EGFR) respectively. The objective of this study was to assess the efficacy of CIX alone or combined with CET in recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) patients. Methods In this open-label phase II trial, 91 R/M HNSCC patients who progressed within 90 days of platinum-based chemotherapy, were randomized to CIX 10 mg/kg alone or with CET 500 mg/m2 every 2 weeks. Patients were stratified by prior CET use. The primary endpoint was median progression-free survival (PFS). Exploratory biomarker assessments included relevant markers on archival tumor and serial cytokine/angiogenic-factor profiles in blood. Results Forty-seven patients were treated with CIX monotherapy and 44 with combination. The median PFS was 1.9 and 2.0 months and clinical benefit rate (complete or partial responses and stable disease) was 5.9% and 15.3%, respectively. There was no exacerbation of CET toxicity by concurrent CIX exposure. Higher tumor expression of IGF-1 was associated with improved PFS in the CIX + CET arm while increased p-EGFR expression correlated with shorter PFS in patients receiving single agent CIX. Higher serum baseline levels of IGF-1 and IGFBP-3 correlated with improved PFS and overall survival (OS) in the CIX arm. Neither regimen resulted in improved PFS or OS compared to historical data with CET alone. Conclusion The results of this study do not support the use of cixutumumab alone or with cetuximab in unselected patients with R/M HNSCC. |
Databáze: | OpenAIRE |
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