• April 20, 2021

Vemurafenib

In a phase I clinical study, vemurafenib (then known as PLX4032) was able to reduce the number of cancer cells in more than half of a group of 16 patients with advanced melanoma. The treated group had a median increase in survival time of 6 months compared to the control group. [15] [16] [17] [18]

A second phase I study, in patients with a V600E mutation in B-Raf, ~ 80% showed partial to complete regression. The regression lasted from 2 to 18 months. [19]

In early 2010, a phase I trial [20] for solid tumors (including colorectal cancer) and a phase II study (for metastatic melanoma) were underway. [twenty-one]

A phase III trial (versus dacarbazine) in patients with previously untreated metastatic melanoma showed an improvement in progression-free and overall survival rates. [22]

In June 2011, positive results were reported from the phase III study of BRIM3 BRAF mutation melanoma. [23] The BRIM3 trial reported good updated results in 2012. [24]

More trials are planned, including a trial of vemurafenib co-administered with GDC-0973 (cobimetinib), a MEK inhibitor. [23] Following good results in 2014, the combination was submitted to the EC and FDA for marketing approval. [25]

In January 2015, trial results compared vemurafenib with the combination of dabrafenib and trametinib for metastatic melanoma. [26]

Side effects
At the maximum tolerated dose (MTD) of 960 mg twice daily, 31% of patients have skin lesions that may require surgical removal. [1] The BRIM-2 trial investigated 132 patients; the most common adverse events were arthralgia in 58% of patients, rash in 52%, and photosensitivity in 52%. In order to better control side effects, some type of dose modification was necessary in 45% of patients. The mean daily dose was 1750 mg, 91% of the MTD. [27]

A trial combining vemurafenib and ipilimumab was stopped in April 2013 due to signs of liver toxicity. [28]

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