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Cetuximab Shows Efficacy in Advanced Non–Small-Cell Lung Cancer

Cetuximab Shows Efficacy in Advanced Non–Small-Cell Lung Cancer

ORLANDO, Florida- Cetuximab (Erbitux) showed activity in patients with advanced non-smallcell lung cancer (NSCLC) who had received prior chemotherapy, including platinum therapy, in a recently completed phase II trial. The efficacy of cetuximab was comparable to that of other agents in this population, according to lead investigator Rogerio C. Lilenbaum, MD, director of the thoracic oncology program at Mount Sinai Comprehensive Cancer Center in Miami Beach, Florida (abstract 7036). For the study, patients received an initial dose of cetuximab at 400 mg/m2 on day 1 of a 4-week cycle, followed by weekly doses of 250 mg/m2 until disease progression or unacceptable toxicity occurred. Good Efficacy, Tolerability Dr. Lilenbaum and colleagues reported three partial responses among the 60 evaluable patients. Median time to progression was 2.3 months and median survival time was 8.1 months.After 6 months, 63.6% of the participants were still alive, and 41.4% were alive after 1 year. "I think this does demonstrate efficacy," said discussant Charles Rudin, MD, PhD, director of the lung cancer therapeutics program at Sidney Kimmel Comprehensive Cancer Center. "The survival rates are reasonably good," he said, and "consistent with our current standard of care." The drug was well tolerated. The principal adverse effects were the flulike symptoms commonly seen with cetuximab, and rash, the investigators said. None of the patients discontinued the drug because of toxicities. Distinct Mechanism of Action Cetuximab is a monoclonal antibody that has been approved by the Food and Drug Administration for treatment of colorectal cancer. Like gefitinib (Iressa) and erlotinib (Tarce-va), which are tyrosine kinase (TK) inhibitors, it targets the epidermal growth factor receptor (EGFR), but its mechanism of action is thought to be different. Cetuximab appears to work by binding to EGFR, thereby blocking growth factors from binding to the receptor and initiating cell growth. Because of the discovery last year that the activity of TK inhibitors is linked to mutations in EGFR, Dr. Lilenbaum and his colleagues looked for an association between these mutations and the response to cetuximab. No clear relationship emerged. Tissue samples from 3 of 39 patients had mutations, all in patients with stable disease; tissue samples were available for two of the three responders, and these were negative for mutations. This finding suggests "that the activity spectrum of cetuximab is likely to be distinct from that of EGFR TK inhibitors," Dr. Rudin said. "We need to begin to look at molecular determinants of cetuximab activity," he added. Next steps for cetuximab may include testing in combination with chemotherapy or other targeted drugs. Dr. Rudin suggested cetuximab with erlotinib and bevacizumb (Avastin), in particular. "I think that this would be a very interesting combination," he said.

 
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