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Institute of Cancer Research - New "Smart" Pill shown to extend lives of patients with most aggressive form of skin cancer

www.icr.ac.uk

6 June 2011

A new pill that precision targets the activity of a faulty gene present in half of terminally ill metastatic melanoma patients has been shown to significantly extend overall survival compared to standard chemotherapy. Data from the BRIM3 study shows that patients with the mutated BRAF gene who were given the twice daily vemurafenib pills were significantly more likely to be alive at 6 months than those receiving dacarbazine.

The Institute of Cancer Research (ICR) was responsible for key research on the BRAF gene, which paved the way for the development of this first-of-its-kind personalised treatment for advanced melanoma.

Based on the significance of the data, the trial was halted early as it was deemed unethical for patients to continue receiving standard chemotherapy and not vemurafenib.

Vemurafenib, a new generation tailored treatment, precision targets the faulty BRAF gene jamming the signal that causes melanomas to grow uncontrollably. Blocking the activity of this gene can cause cancer cells to die and tumours to shrink. All cancers are different in their genetic properties and therefore patients respond differently to treatment. Vemurafenib presents an opportunity to personalise the treatment approach for metastatic melanoma.

Vemurafenib is not currently licensed and the diagnostic test for BRAF mutation is not currently commercially available. The pill, previously known as PLX4032 or RG7204, was recently filed with both the European Medicines Agency (EMA) and US Food and Drug Administration (FDA) who will review it over the coming months for licensing.

Dr James Larkin, UK Principal Investigator for BRIM 3 from The Royal Marsden, said: “Without question, the results of this trial represent a turning point in the treatment of this disease. Vemurafenib targets the faulty BRAF protein which is present in 50% of melanomas and this trial has shown that vemurafenib significantly prolongs life in comparison with chemotherapy”.

Over the past twenty-five years, rates of malignant melanoma in Britain have risen faster than any other common cancer. It is now the second most common cancer in young adults (aged 15-34) in the UK, affecting almost twice as many young women as young men, although men are more likely to die from it.

Professor Richard Marais, whose work at the ICR demonstrated the importance of BRAF in melanoma, said: “This is the biggest breakthrough in melanoma treatment in more than 30 years. The results demonstrate for the first time that a targeted therapy can work in melanoma and will change our approach to treating this disease. It is an enormous advance in the field.”

Further trials are underway exploring the use of vemurafenib in a variety of other cancers including ovarian, thyroid and colorectal cancer. In conjunction Roche and partner company Plexxikon have developed a diagnostic test to determine whether patients have the faulty BRAF gene, which could deliver results in a matter of days.

The most frequent grade 3 adverse events with vemurafenib were skin related and included cutaneous squamous cell carcinoma, a common skin cancer treated by local excision. Additionally, generally mild and reversible increases in liver enzymes (GGT, ALT, AST, alkaline phosphatase, and bilirubin) were observed in some patients.

The most common adverse events were rash, photosensitivity, joint pain, hair loss and fatigue.