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
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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