Vemurafenib has recently been added to the Pharmaceutical Benefits Scheme (PBS) for the treatment of unresectable Stage III or Stage IV malignant melanoma in combination with cobimetinib. Vemurafenib is an orally active inhibitor of some mutated forms of the BRAF kinase enzyme. Around 50% of melanomas contain activating BRAF V600 mutations that can result in uncontrolled cellular proliferation.

A randomised phase 3 trial investigated the efficacy of vemurafenib using dacarbazine as the comparator. At six months, the overall survival in the vemurafenib group was 84% compared to 64% for the comparator. Progression-free survival was estimated to be 5.3 months for vemurafenib-treated patients and 1.6 months for dacarbazine. Head-to-head trials have not been conducted comparing vemurafenib to the other PBS listed BRAF inhibitor, dabrafenib.

Tumour regrowth may follow initial tumour regression due to acquired resistance. A suggested strategy to avoid the development of resistance is to combine therapy with a mitogen-activated protein kinase (MEK) inhibitor such as cobimetinib. This combination was investigated in the coBRIM trial. Progression-free survival increased from 6.2 months in the vemurafenib group to 9.9 months in the combination group.

Common adverse effects of vemurafenib include photosensitivity, peripheral oedema, prolonged QT interval, and raised liver enzymes. Secondary malignancies may also occur, usually in the form of cutaneous squamous cell carcinomas. However, new primary malignant melanomas have also been reported. Routine dermatologic evaluation should occur during therapy and for up to six months after ceasing vemurafenib.

References:

  1. Chapman PB, Hauschild A, Robert C, Haanen JB, Ascierto P, Larkin J, et al. Improved survival with vemurafenib in melanoma with BRAF V600E mutation. N Engl J Med. 2011; 364: 2507.
  2. Dupati A, Gill L. Vemurafenib: background, patterns of resistance, and strategies to combat resistance in melanoma. Medical Student Research Journal 2014; 3: 36-43.
  3. Flaherty KT. Vemurafenib: a first in class serine-threonine protein kinase inhibitor for the treatment of malignant melanoma with activating BRAF mutations. New York: Medscape; 2011.
  4. Larkin J, Ascierto PA, Dréno B, Atkinson V, Liszkayy G, Maio M, et al. Combined vemurafenib and cobimetinib in BRAF-mutated melanoma. N Engl J Med. 2014; 371: 1867-76.
  5. Zelboraf® (vemurafenib) Australian approved product information. Dee Why: Roche Products. Approved June 2017.

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