The new combination of drugs for advanced melanoma with the BRAF mutation is very effective and extends the survival of patients to over 33 months – says Prof. Reinhard Dummer from the University of Zurich. Patients who cannot tolerate older drug combinations now have a new treatment option.
Advanced melanoma is considered to be one of the most dangerous malignant neoplasms. Although for about eight years there has been a huge progress in its treatment (thanks to the use of the so-called immunotherapy and BRAF and MEK inhibitors), approx. patients with advanced melanoma still cannot be saved. Therefore, scientists are still looking for new therapeutic options.
– Thanks to the new combination of drugs, the effectiveness of treatment of patients with advanced melanoma with BRAF mutation is increasing – he emphasized in an interview with Prof. Dummer – the lead author of the study with the acronym COLUMBUS, the latest results of which were presented at the session with the most important news at the annual meeting of the American Society of Clinical Oncology ASCO, held June 1-5 in Chicago. The ASCO Congress is the world’s largest meeting regarding new achievements in the treatment of cancer patients.
The Phase III COLUMBUS trial enrolled a total of 921 patients with advanced (unresectable or metastatic) melanoma and the BRAF V600 mutation. It occurs in about half of patients with melanoma.
Some of the study participants received a combination of two new drugs, the so-called COMBO40: a second generation BRAF inhibitor called encorafenib and a MEK inhibitor called binimetinib. For comparison, some patients were administered only encorafenib or the first generation BRAF inhibitor called vemurafenib.
Compared to vemurafenib, the combination of the two new drugs reduces the risk of death from advanced melanoma by almost 40%. This was demonstrated by the latest data analysis, the results of which were presented at the ASCO. The mean survival of patients receiving COMBO40 was 33,6 months and it was almost twice as long as in the group receiving vemurafenib (less than 17 months). According to oncologists, extending the survival of patients with advanced melanoma with BRAF mutation to more than 30 months is a big progress.
Almost 60 percent patients receiving a new combination of drugs lived for two years. The combination was also more effective than administering encorafenib alone, with a median survival of 23,5 months.
Prof. Dummer noted that the new drug combination is so far the best when compared to other treatments that consist of a BRAF inhibitor and a MEK inhibitor (vemurafenib plus cobimetinib or dabrafenib plus trametinib).
The specialist noted that from a scientific point of view, the results of studies on these drug combinations are difficult to compare. However, it is tempting to do so, as all of them – as part of the control – were compared to treatment with vemurafenib only.
Importantly, the combination of the two new drugs is generally well tolerated by patients. Side effects occur in a smaller percentage of patients using the two drugs than in the group using only the BRAF inhibitor (vemurafenib or encorafenib). Compared to the older combinations, for example, fever and photosensitivity of the skin occur less frequently.
– It is important for patients that the side effect profile of the new combination of drugs is different than that of the older combinations – explained Prof. Dummer. For example, vemurafenib therapy causes severe skin photosensitivity. In turn, 40 percent. patients treated with the combination of dabrafenib and trametinib have recurring episodes of fever. – This causes discomfort for patients and is confusing for doctors who think the patient is suffering from an infection – explained the specialist.
He noted that those patients who cannot tolerate older drug combinations now have a new treatment option.
In 40, the manufacturer COMBO2017 submitted an application to the European Medicines Agency (EMA) regarding the approval of the new therapy in EU countries. The application was based on the results of the so-called progression-free survival (ie without cancer progression), which have been published in the journal Lancet Oncology.
Melanoma is the most malignant neoplasm of the skin and mucous membranes, originating from melanocytes of pigmented nevi or unchanged skin. It arises as a result of their excessive stimulation due to exposure to ultraviolet radiation, and gives early metastases both through the lymphatic and blood vessels.