Lay Summary: Erbitux is proving to be an active and important agent for lung cancer.
Erbitux binds specifically to epidermal growth factor receptors on both normal and tumor cells, and competitively inhibits the binding of epidermal growth factor and other ligands. It is approved for use in combination with irinotecan to treat patients with EGFR-expressing metastatic colorectal cancer who are refractory to irinotecan-based chemotherapy and as a single agent in the patients intolerant to irinotecan-based chemotherapy; aslo approved for head and neck. There is less information on its use in lung cancer.
Two single-arm phase II trials testing cetuximab in combination with a platinum-based doublet in previously untreated patients showed responses in the range of 26% to 29%, with median survival times of 10 to 11 months.
A Phase III study of ERBITUX® (Cetuximab) in combination with platinum-based chemotherapy (vinorelbine plus cisplatin) met its primary endpoint of increasing overall survival compared with chemotherapy alone in patients with advanced non-small cell lung cancer (NSCLC). This large, randomized multi-national study, known as FLEX (First-Line Treatment for Patients with Epidermal growth factor inhibitor (EGFR)-EXpressing Advanced NSCLC) was conducted by Merck KGaA, Darmstadt, Germany and enrolled patients with Stage IIIB or Stage IV NSCLC who had not previously received chemotherapy. The results were announced in September on 2007 and published in December.Overall survival was 11.3 months in the cetuximab arm versus 10.1 months in the controls (HR-0.871, P =0.044). One year survival was 47% in the cetuximab arm versus 42% in controls. Prespecified ethnic analyses revealed a more impressive response in 946 Caucasian patients-a 10.5-month median overall survival for cetuximab versus 9.1 months (HR 0.803, P =0.003). Median progression-free survival (which was the prospective endpoint) was not different at 4.8 months in both arms.
This is the relevent summary describes what should be considered medically appropriate use of Erbitux: ” First-line therapy for recurrence or metastasis in combination with vinorelbine and cisplatin for performance status 0-2 patients at least 18 years of age with NSCLC IIIB (pleural effusion)/IV, EGFR expression by immunohistochemistry (at least 1 positive tumor cell), no known brain metastases, and no prior chemotherapy or anti-EGFR therapy. ”
Does this recommendation apply to second line therapy? Abstract of a study presented at the 2003 ASCO annual meeting that found cetuximab in combination is well tolerated and the response rate suggests clinical activity in the second-line settingm and this was with Docetaxel. I do not consdier evidence for second line to be conclusive and more studies need to be done.
Pirker, R et al “FLEX: A randomized, multicenter, phase III study of cetuximab in combination with cisplatin/vinorelbine (CV) versus CV alone in the first-line treatment of patients with advanced non-small cell lung cancer (NSCLC)” Abstract 3 ASCO 2008
nccn.org, lung cancer
Kvale PA, Selecky PA, Prakash UB, American College of Chest Physicians. Palliative care in lung cancer: ACCP evidence-based clinical practice guidelines (2nd edition). Chest 2007 Sep;132(3 Suppl):368S-403S. [358 references]
Cetuximab in Advanced Non-Small Cell Lung Cancer
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