Targeted Initial Therapy for Melanoma
Genomic testing for recurrent “driver” mutations known to cause and sustain tumor growth is particularly important in melanoma due to the availability or development of targeted therapies. "Jorge" was able to start initial therapy with a BRAF inhibitor that had promising results in early clinical trials.
In this molecular profile, our fictional patient, Jorge, is a 40 year-old man who visited his doctor because of a growing skin lesion on his back. He was diagnosed with superficial spreading melanoma (SSM) that had metastasized to his lungs. Molecular testing revealed a common BRAF mutation.
- Mutations in BRAF are found in as many as 50% of cases of metastatic melanoma; the V600E mutation is the most common mutation seen.
- BRAF mutations are more commonly found in the superficial spreading melanoma (SSM) and nodular melanoma (NM) subtypes; they are also more common in primary lesions of the trunk and in patients younger than 50 years at the time of presentation.
- In a phase III trial of vemurafenib, a small molecule inhibitor of BRAF, in patients with previously untreated melanoma with the BRAF V600E mutation, overall survival was 84% in the vemurafenib group vs. 64% in the dacarbazine group. Vemurafenib was associated with a relative reduction of 63% in the risk of death and of 74% in the risk of either death or disease progression, as compared with dacarbazine
- PLX4032 (now known as vemurafenib) is now approved for the treatment of patients with unresectable or metastatic melanoma with BRAFV600E mutation.
- Clinical trials of several other inhibitors of BRAF are currently enrolling patients.
- Flaherty KT. Narrative review: BRAF opens the door for therapeutic advances in melanoma. Ann Intern Med. 2010;153:587-91.
- Chapman, et al. Improved Survival with Vemurafenib in Melanoma with BRAF V600E Mutation. N Engl J Med 2011; 364:2507-2516
Note: This fictional, composite story, which includes data from actual representative patient cases, conveys how information from comprehensive genomic testing may impact treatment for management and care of people suffering from cancer.