Melanomas that develop resistance to vemurafenib also become addicted to the drug

Vemurafenib (marketed as Zelboraf) is a B-Raf enzyme inhibitor developed by Plexxikon (now part of the Daiichi Sankyo group) and Hoffmann–La Roche for the treatment of late-stage melanoma. The name "vemurafenib" comes from V600E mutated BRAF inhibition.

Vemurafenib received FDA approval for the treatment of late-stage melanoma on August 17, 2011,  Health Canada approval on February 15, 2012 and on February 20, 2012, the European Commission approved vemurafenib as a monotherapy for the treatment of adult patients with BRAF V600 mutation positive unresectable or metastatic melanoma, the most aggressive form of skin cancer....

Mechanism : Vemurafenib has been shown to cause programmed cell death in melanoma cell lines. Vemurafenib interrupts the B-Raf/MEK step on the B-Raf/MEK/ERK pathway if the B-Raf has the common V600E mutation.

Vemurafenib only works in melanoma patients whose cancer has a V600E BRAF mutation (that is, at amino acid position number 600 on the B-Raf protein, the normal valine is replaced by glutamic acid). About 60% of melanomas have this mutation. It also has efficacy against the rarer BRAF V600K mutation. Melanoma cells without these mutations are not inhibited by vemurafenib; the drug paradoxically stimulates normal BRAF and may promote tumor growth in such cases. 

Melanomas that develop resistance to vemurafenib also become addicted to the drug

FDA Approves Zelboraf - Potent New Melanoma Drug

Plexxikon Inc., a member of the Daiichi Sankyo Group, today announced that applications for market approval for vemurafenib ( PLX4032/RG7204, see below structure) for the treatment of metastatic melanoma have been submitted to the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA). The company had 

Phase 2 and 3 trials (BRIM2 and BRIM3) that evaluated vemurafenib in patients with BRAF ^V600 mutation-positive melanoma, as determined by the cobas 4800 BRAF ^V600 Mutation Test.

 Earlier this year, the company reported positive data from an interim analysis of BRIM3 which showed that the study met the pre-specified criteria for co-primary endpoints for BRIM3 for progression-free survival and overall survival, and that the safety profile was generally consistent with the previous vemurafenib studies. Based on these results, the data safety monitoring board for the trial recommended early termination of the trial and allowed dacarbazine-treated patients to immediately cross over to vemurafenib treatment. BRIM2 results reported earlier showed a 52 percent confirmed response rate, with tumor shrinkage in the majority of patients, consistent with results from earlier studies. 

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