On November 7, the FDA approved cetuximab (Erbitux) in combination with platinum-based therapy plus fluorouracil (5-FU) for the first-line treatment of patients with recurrent locoregional disease and/or metastatic squamous cell carcinoma of the head and neck. The approval was based primarily on the results of a multicenter clinical study conducted outside the United States in 442 patients with metastatic or locally recurrent head and neck cancer who were not suitable for potentially curative treatment with surgery or radiation.
The study used a European Union (EU)-approved cetuximab rather than the U.S.-approved cetuximab (Erbitux). Erbitux provides approximately 22% higher exposure relative to the EU-approved cetuximab; these pharmacokinetic data, together with the results of the study conducted in Europe and other clinical trial data using Erbitux establish the safety and efficacy of Erbitux at the recommended dose.
The trial enrolled 442 patients; 222 patients received cetuximab plus cisplatin (or carboplatin) with 5-FU and 220 patients received cisplatin (or carboplatin) with 5-FU. The median follow-up at the time of overall survival analysis was 19.1 and 18.2 months for the cetuximab-plus-chemotherapy arm and the chemotherapy-alone arm, respectively.
Overall survival was significantly improved in patients receiving cetuximab plus chemotherapy compared to those receiving chemotherapy alone (10.1 vs 7.4 months; HR = 0.80; 95% CI = 0.64–0.98; P = .034). Progression-free survival was also significantly improved in patients receiving cetuximab plus chemotherapy (5.5 vs 3.3 months; HR = 0.57; 95% CI = 0.46–0.72; P < .0001). Objective response rates were 35.6% and 19.5% (odds ratio = 2.33; 95% CI = 1.50–3.60; P = .0001) in the cetuximab-plus-chemotherapy and the chemotherapy-alone arms, respectively.
The most common adverse reactions in patients treated with cetuximab plus chemotherapy were nausea, anemia, vomiting, neutropenia, rash, asthenia, diarrhea, and anorexia. Other adverse reactions, sometimes severe, caused by cetuximab included infusion reactions, hypomagnesemia, hypocalcemia, and hypokalemia. Health care providers should closely monitor serum electrolytes, including serum magnesium, potassium, and calcium, during and after cetuximab administration.
The approved dose of Erbitux is 400 mg/m2 intravenously as an initial dose, followed by 250 mg/m2 intravenously weekly in combination with cisplatin or carboplatin plus continuous infusion 5-FU.
Erbitux was first approved by the FDA in 2004 to treat epidermal growth factor receptor–positive late-stage colon cancer after patients stopped responding to chemotherapy, and has been approved since 2006 for treatment of nonmetastatic head and neck cancer. ■