New hope for patients whose melanoma has metastasised to the brain

www.roche.co.ukNov 18 2013

New data show that in patients whose melanoma (BRAF V600 mutation-positive) has spread (metastasised) to the brain, Zelboraf (vemurafenib) extends life expectancy by over six months compared to chemotherapy.¹ These results are welcome news for patients suffering from metastatic melanoma, as up to half of these patients are diagnosed with brain metastases with many given less than six months to live.¹

Results presented today at the International Meetings of the Society for Melanoma Research (SMR) show that patients on vemurafenib have overall survival rates of 6.47 months in patients with previously untreated brain metastases and 6.41 months in previously treated patients.¹

Dr Paul Nathan, study author and Consultant Medical Oncologist from Mount Vernon Cancer Centre, UK said: “Advanced melanoma is an aggressive cancer affecting many patients who are in the prime of their lives. Melanoma is one of the most likely cancers to spread to the brain and unfortunately the outcome for these patients is currently very poor. Therefore, these data represent an encouraging step forward in providing new treatment options for patients with brain metastases.”

As part of the continuing study of vemurafenib in skin cancer, additional data at SMR show that the treatment also extends life beyond one year for BRAF metastatic melanoma patients.² Updated BRIM3 data (33 months follow-up) show that overall survival for vemurafenib was 13.6 months (95% CI 12.0−15.3) vs 9.7 months for chemotherapy (95% CI 7.9−12.8).²

Dr James Larkin, UK BRIM3 lead researcher from The Royal Marsden said:

“The availability of a personalised therapy represents a step change in the way we now manage metastatic melanoma, and these new data continue to show how vemurafenib helps patients survive longer. This increasing clinical and real-world experience with vemurafenib is helping us better understand treatment options for this aggressive form of cancer.”

Other data at SMR showed that the combination of vemurafenib and cobimetinib, a MEK inhibitor, continues to show promising initial results. BRIM7, an open-label, Phase 1b study has shown that the investigational combination can be safely administered together and that the preliminary efficacy is encouraging. Recruitment for a Phase 3 trial is ongoing and the primary results of the study are due to be reported in 2014. New options in this patient population are important given metastatic melanoma is incurable.³

Vemurafenib was licensed for use in patients with BRAF V600 mutation positive unresectable or metastatic melanoma, in the UK in February 2012 and approved by NICE in December 2012.⁴ It was developed based on research conducted at The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research.⁶

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.⁵ The most common adverse events reported with vemurafenib include arthralgia, fatigue, rash, photosensitivity reaction, nausea, alopecia and pruritus. Cutaneous Squamous Cell Carcinoma (CuSCC) was very commonly reported and was most commonly treated by local excision.⁴

Malignant melanoma disproportionately affects young people and is now the second most common cancer in people aged 15-34 in the UK. Rates of malignant melanoma in Britain have risen faster than any other common cancer, with an estimated 2,000 people dying from the skin cancer annually in this country.⁷ It is estimated that overall cases of melanoma will rise by 52% by 2030 - the biggest projected increase of any other cancer.⁸

References

1. Kefford, R et al. Vemurafenib in Metastatic Melanoma Patients With Brain Metastases: An Open-Label, Single-Arm, Phase 2, Multicenter Study. Presented at the 10th International Meeting of the Society for Melanoma Research; November 17-20, 2013; Philadelphia, Pennsylvania
2. Hauschild, A et al. Vemurafenib Improves Overall Survival Compared With Dacarbazine in Advanced BRAFV600-Mutated Melanoma: Updated Results From a Phase 3 Randomized, Multicenter Trial. Presented at the 10th International Meeting of the Society for Melanoma Research; November 17-20, 2013; Philadelphia, Pennsylvania
3. Daud, A et al. Phase IB (BRIM7) results combining vemurafenib (VEM) and cobimetinib, a MEK inhibitor, in patients (pts) with advanced BRAFV600- mutated melanoma. Presented at the 10th International Meeting of the Society for Melanoma Research; November 17-20, 2013; Philadelphia, Pennsylvania
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5. Royal Marsden. Research highlights. Available from: http://www.royalmarsden.nhs.uk/research/highlights/pages/vemurafenib.aspx [Last accessed: November 2013]
6. Chapman PB, Hauschild A et al. Improved survival with vemurafenib in melanoma with BRAF V600E mutation. The New England Journal of Medicine. 2011;364:2507-16
7. Cancer Research UK. Skin cancer statistics – Key Facts. Available from: http://info.cancerresearchuk.org/cancerstats/types/skin/  [Last accessed: November 2014]
8. Mistry M, Parkin D M, Ahmad A S and Sasieni P, Cancer incidence in the United Kingdom: projections to the year 2030, British Journal of Cancer, 27 October 2011
9. Algazi AP, Soon C et al. Treatment of cutaneous melanoma: current approaches and future prospects. Journal of Cancer Management and Research. 2010;2:197-211
10. Rigel D. Malignant melanoma: Perspectives on incidence and its effects on awareness, diagnosis, and treatment. CA: A Cancer Journal for Clinicians. 1996:46:195-198
11. Korn EL, Ping-Yu L et al. Meta-analysis of phase II cooperative group trials in metastatic stage IV melanoma to determine progression-free and overall survival benchmarks for future phase II trials. Journal of Clinical Oncology. 2008;26:527-534
12. Cancer Research UK. Two young adults diagnosed with skin cancer every day. Available from http://info.cancerresearchuk.org/news/archive/pressrelease/2011-04-06-two-young-adults-diagnosedskin-cancer-each-day [Last accessed: November 2013]