Vemurafenib Improves Survival for Patients with Metastatic MelanomaPatients with metastatic melanoma whose tumors harbor a specific genetic mutation have improved overall survival with the targeted therapy vemurafenib (Zelboraf), according to longer-term follow-up data from a phase II clinical trial published in the February 23 issue of the New England Journal of Medicine. The mutation, the V600 mutation in the BRAF gene, is found in approximately half of patients diagnosed with melanoma.
After a median follow-up of almost 13 months, median overall survival was nearly 16 months in the trial of 132 patients whose cancer was no longer responding to standard treatments—a substantial improvement over the 6- to 10-month median survival traditionally seen in patients with metastatic melanoma. The median progression-free survival was 6.8 months.
Last year, based on the impressive early results of a large phase III trial, the Food and Drug Administration approved vemurafenib for the treatment of patients with metastatic disease whose tumors have this mutation.
In the current trial—funded by the drug’s manufacturer, Roche—a tumor response was observed in more than half of the patients, with 6 percent of patients experiencing a complete response. Most patients whose tumors responded to treatment saw their tumors shrink within 2 months.
Most patients taking the drug will ultimately develop resistance, said the study’s lead author, Dr. Jeffrey Sosman of Vanderbilt-Ingram Cancer Center in Tennessee. But a subset of patients, he noted, have shown no signs of progression even 2 years after beginning treatment.
The drug is generally well tolerated, the researchers reported. Nevertheless, 45 percent of patients had their dose of the drug reduced, and nearly two-thirds had to have their treatments temporarily stopped, because of side effects. Common side effects included rash, joint pain, and extreme sensitivity to light. And, as has been seen in other trials of vemurafenib, approximately one-quarter of patients developed cancerous or precancerous non-melanoma skin lesions.
In most of these patients, only one or two lesions were found, and in all cases they could be removed easily with surgery, Dr. Sosman said.