Combination treatment prevents disease progression in patients with advanced melanoma

Sep 30 2014

New pivotal data support potential for MEK inhibitor cobimetinib, in combination with established BRAF inhibitor Zelboraf^®▼ (vemurafenib), to help melanoma patients live longer without their disease worsening by half

New data announced today has demonstrated that combinational treatment of cobimetinib with Zelboraf^® (vemurafenib), the first personalised medicine to extend life in the first-line setting for over 30 years, in patients with advanced melanoma (BRAF^V600 mutation-positive) can prevent disease progression (progression-free survival; PFS) by 9.9 months compared to 6.2 months following treatment of vemurafenib alone.

The results presented at the European Society for Medical Oncology (ESMO) Congress today show that patients treated with cobimetinib in combination with vemurafenib reduces the risk of their disease worsening by half (49%). In addition, the study found that the objective response rate (tumour response to treatment) was higher in the combination compared to vemurafenib alone (68% vs. 45%). This expands on the wealth of data for vemurafenib, which was launched in 2012 as the first BRAF inhibitor proven to extend overall survival in this patient population by over one year.

Dr James Larkin, Consultant Medical Oncologist at The Royal Marsden and Lead Investigator for the trial, said:

We are delighted to have been able to further explore the treatment options for patients with advanced melanoma. This data could represent a significant step forward in the treatment of this disease. The data shows that the combination of vemurafenib with cobimetinib prolongs progression-free survival significantly in comparison with vemurafenib alone. Not only that but it also shows that the side effects are generally manageable, which is incredibly important for our patients. Vemurafenib has been hailed as one of the biggest breakthrough treatments for malignant melanoma in the past 30 years and in just three years we have been able to make major strides in improving on its effectiveness as a treatment for patients. This latest trial is helping to cement The Royal Marsden as a global leader in this field of research.

“This data announcement for cobimetinib represents positive progress for the thousands of patients in the UK who are suffering from melanoma, said Charlotte Fionda, from Skcin, the Karen Clifford Skin Cancer Charity. “Melanoma is a devastating disease for patients and their families and there is a real need for additional and efficacious combination treatments, which if approved, have the potential to give additional time to those affected.”

The findings presented at ESMO are the results of CoBRIM, an international randomised, double-blind, placebo-controlled Phase 3 study evaluating the safety and efficacy of cobimetinib in combination with vemurafenib, compared to vemurafenib alone. This study included patients from nine English trial centres out of 11 based in the UK. In addition, the latest data follows further evidence stemming from the open-label, Phase 1b study (BRIM7), which initially showed that the combination of cobimetinib and vemurafenib can be safely co-administered and had demonstrated anti-tumour activity.

The safety profile of the CoBRIM study was also consistent with the BRIM7 study. The most common adverse events observed in the combination arm compared to vemurafenib alone included diarrhoea (57% vs. 28%), nausea (39% vs. 24%), photosensitivity (28% vs. 16%), liver lab abnormalities (increased alanine aminotransferase [24% vs. 18%], increased aspartate aminotransferase [22% vs. 13%]), increase in creatine phosphokinase (an enzyme released by muscles, 30% vs. 3%) and vomiting (21% vs. 12%).

There has been a significant rise in melanoma cases in recent years. It is estimated that 13,300 people developed the condition in the UK in 2011, equating to 37 people every day, compared to 1,800 in 1975. Advances in treatment have meant that more than eight in ten people with melanoma survive for five years or longer following their diagnosis. However, latest statistics tell us that approximately 2,000 malignant melanoma patients die every year, making continued research and development in this therapy area essential.