In a nutshell
In this phase 3 clinical trial, researchers compared the safety and efficacy of vemurafenib to the standard chemotherapy drug for melanoma, dacarbazine.
Some background
A genetic defect (mutation) in protein called BRAF is present in approximately 50% of melanomas. BRAF helps cells grow and multiply, so BRAF mutations are responsible for the rapid growth of melanomas. Certain drugs can target the BRAF protein and block its action (targeted therapies), thus stopping the uncontrolled growth of BRAF-mutated melanomas. A standard treatment for melanoma is the chemotherapy drug dacarbazine. However, new targeted therapies show promise in treating patients with metastatic (cancer that has spread to the lymph nodes or to distant organs and tissues) melanoma. Vemurafenib (Zelboraf) is such a targeted therapy drug that has been approved by the U.S. FDA for the treatment of patients with metastatic melanoma.
Methods & findings
Researchers recruited 675 metastatic melanoma patients with the most common BRAF mutation, called BRAFV600E. Of these, 337 patients received vemurafenib and 338 received dacarbazine. After six months of treatment, progression-free survival (the percentage of patients who have survived for a defined period of time, without progression of their cancer) was higher in the vemurafenib group than the dacarbazine group (5.3 months versus 1.6 months). Almost all patients in the vemurafenib group had reduced cancer size, but less than half of patients in the dacarbazine group had reduced cancer size. Confirmed responses were observed in 48% of vemurafenib-treated patients, compared to only 5% of dacarbazine-treated patients. Furthermore, overall survival (defined as the percentage of patients who have survived for a certain period of time after treatment) was higher in patients treated with vemurafenib (84%), compared to those who received dacarbazine (64%). However, there were more side effects in the vemurafenib group such as skin reactions, joint pain or hair loss. Also, 18% of vemurafenib patients developed new skin cancers (squamous cell carcinoma or keratoacanthoma).
The bottom line
In summary, vemurafenib reduced cancer size and increased survival rates in patients with metastatic melanoma and BRAF mutations.
The fine print
This study was funded by Hoffmann–La Roche, the manufacturer of Zelboraf.
This study served as grounds for the FDA approval of Zelboraf for the treatment of patients with metastatic melanoma.
Published By :
The New England Journal of Medicine
Date :
Jun 05, 2011
