Novartis launches first targeted combination treatment for advanced melanoma in the UK, but immediate access for patients uncertain

Novartis has announced that Tafinlar® (dabrafenib) + Mekinist® (trametinib), the first oral targeted combination therapy to be licensed for advanced melanoma, is now available in the UK, for the treatment of adult patients with unresectable or metastatic melanoma with a BRAF V600 mutation.^1,2

However, for patients with the most aggressive form of skin cancer, access to the new combination is uncertain. Guidance from the National Institute for Care Excellence (NICE) will not be available until the second half of 2016, and NHS England has announced that no new medicines will be listed through the Cancer Drugs Fund until at least April 2016.

Metastatic melanoma is the most serious and life-threatening type of skin cancer³, with only a 20% survival rate five years after diagnosis.⁴ There are more than 13,000 cases of malignant melanoma diagnosed every year in the UK, around 37 a day.⁵ Both incidence and mortality have continued to rise over the past three decades, with incidence rising faster than that for the ten most common cancers.⁵ It has been predicted that within a decade, melanoma will be the fourth most common cancer for men and women in the UK.⁶

Like many cancers, abnormal gene changes (mutations) can lead to the development of melanoma. Approximately half of all melanoma cases have a BRAF mutation⁷, which can be determined by genetic testing of the tumour so the most appropriate targeted treatment can be chosen.⁴

The BRAF mutation results in abnormal activity of certain proteins that are part of a pathway within the skin cell responsible for regulating cell growth and development.⁷ This leads to uncontrolled cell growth and tumour development. The combination of dabrafenib + trametinib targets two different proteins in the pathway to inhibit their activity, and has been shown to slow tumour growth more effectively than BRAF inhibitor monotherapy.^8,9

"Understanding what drives melanoma at a genetic level has transformed the way we treat this devastating cancer and this combination is an important new option for patients. It has been shown to be more effective than monotherapy in extending the time to cancer progression and for the first time we are seeing median overall survival of more than two years," said Dr Paul Nathan, Consultant Medical Oncologist, Mount Vernon Cancer Centre, Middlesex. "But equally important for patients is their quality of life. The studies of this combination also demonstrate an improvement in quality of life and an acceptable safety profile, which is crucial for patients with advanced melanoma."

Access uncertainty from the start

Despite the UK launch, the prospect of patients gaining access to this combination therapy immediately looks bleak following the announcement in July that no new drugs will be included on the CDF list for the foreseeable future.

"While the CDF was not sustainable, it was the only mechanism by which new cancer medicines could get funding between launch and an appraisal by NICE", said Margaret Dean, General Manager, Novartis Oncology UK and Ireland. "It is unfortunate that the CDF is closed to all new cancer medicines - with no transition mechanism in place. What this means for the first oral targeted combination therapy for advanced melanoma is that no patients can benefit from July 2015 until April 2016 at the earliest and patients are falling through the gap."