Cetuximab in metastatic or recurrent head and neck cancer: the EXTREME trial

Abstract

Expression of EGF receptor (EGFR) is frequently elevated in squamous cell carcinoma of the head and neck (SCCHN). Cetuximab is an anti-EGFR monoclonal antibody that has been shown to improve overall survival in patients with locally advanced SCCHN when combined with radiotherapy. Data from Phase II trials suggest an interesting activity of cetuximab in patients with recurrent or metastatic SCCHN who are refractory to cisplatin. The Erbitux in First-Line Treatment of Recurrent or Metastatic Head and Neck Cancer (EXTREME) Phase III trial compared platin-5-fluorouracil alone versus combined with cetuximab as first-line treatment in recurrent or metastatic SCCHN. In the cetuximab arm of this study, a significant improvement in the overall survival (the main objective), progression-free survival and response rate were observed. The quality of life analyses (QLQ-C30 and QLQ-H&N35) showed no significant differences in most of the studied scores between the two treatment arms. Nevertheless, patients in the cetuximab arm displayed significant improvements in pain, swallowing problems and scores for speech and social eating problems. The results of the EXTREME study (and other studies evaluating cetuximab for the treatment of SCCHN) suggest a lack of a predictive value for the expression of EGFR (determined by immunohistochemistry) by the tumor and other biomarkers need to be investigated. The role of other targeted drugs and of possible combinations of these new drugs with cetuximab should be investigated in properly designed preclinical studies and clinical trials.

Gefitinib, Methotrexate and Methotrexate plus 5-Fluorouracil as palliative treatment in recurrent head and neck squamous cell carcinoma

“…A recently published phase III EXTREME study showed that adding Cetuximab (human chimeric monoclonal antibody against EGFR) to platinum and 5-FU significantly prolonged the median OS from 7.4 months to 10.1 months in recurrent and/or metastatic SCCHN. 24 Quality of life (QOL) measurement was done with a recently developed instrument, the Functional Assessment of Cancer Therapy-Head & Neck Symptom Index-10 (FHNSI-10). It is a 10 item symptom-focused index specially designed for advanced and/or recurrent/refractory head and neck cancer.…”

Health-related quality of life and cancer clinical trials

“…Other cancers A comparison of platin-5-fluorouracil alone versus combination with cetuximab as first-line treatment in recurrent or metastatic squamous cell cancer of the head and neck region showed no significant differences in most HRQOL scores between the two treatment arms, but patients in the cetuximab arm displayed significant improvements in pain, swallowing problems, speech and social eating problems [Rivera et al 2009].…”

Combined chemotherapy and intensity-modulated radiotherapy for the treatment of head and neck cancers

“…Proof of principle was obtained in a Phase III study of first line cisplatin plus cetuximab, which demonstrated improved overall survival in metastatic head and neck cancer patients [38]. Wirth et al investigated the feasibility of combining panitumumab, carboplatin and two dose levels of paclitaxel with radiation delivered using IMRT as primary treatment in patients with advanced head and neck cancer [39].…”