Paul B. Chapman, MD, medical oncologist, Memorial Sloan-Kettering Cancer Center, discusses combination therapy with dabrafenib and trametinib, two investigational agents for patients with advanced melanoma that have a V600 

An expanded Phase IB trial to be presented as ASCO shows that combination therapy with the BRAF inhibitor dabrafenib and the MEK inhibitor trametinib stalls cancer progression with fewer side effects than a single-agent BRAF-targeted therapy.

Based on the rational behind this trial, Chapman is optimistic that this combination will result in a prolonged response. With a single BRAF inhibitor, approximately half of patients develop resistant within five to six months. With the addition of the MEK inhibitor, ideally the time to resistance would be increased, but this data has not yet matured.

As more data becomes available, Chapman hopes that this combination results in a higher response rate or a higher incidence of complete responses. A larger trial is likely to follow, but the the phase IB trial has set the stage for the efficacy of this combination.

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Dr. Paul Chapman, from Memorial Sloan-Kettering Cancer Center, on Combining BRAF and MEK Inhibitors for Advanced Melanoma

Dr. Chapman on BRAF/MEK Combination for Melanoma

Paul Chapman, MD, from Memorial Sloan-Kettering Cancer Center, discusses clinical trials with vemurafenib and the future combination therapies that will be available with the drug.

Vemurafenib is a BRAF enzyme inhibitor for the treatment of late-stage melanoma, specifically recommended for patients whose tumors have 

 gene. It is estimated that this type of 

 mutation is present in 50% of patients with melanoma.

Currently, there are already trials with other targeted agents and there are BRAF plus MEK inhibitor trials. In the future, there will be MEK inhibitor trials with drugs that block other pathways, like the PI3-Kinase Pathway.

An unprecedented aspect of the vemurafenib drug is that researchers believe they understand the mechanism of its action, which will allow them to develop combinations of therapy in a more rational way rather than the older practice of combining drugs in a way that might be thought helpful. With vemurafenib, doctors can make intelligent and more informed choices by knowing which pathways they have to block.

Dr. Chapman from Memorial Sloan-Kettering Cancer Center on Vemurafenib Combination Therapies

Dr. Chapman on Vemurafenib Combination Therapies

Paul Chapman, MD, From Memorial Sloan-Kettering Cancer Center describes recent melanoma advances.

Dr. Chapman says there are now two drugs that improve survival in patients with metastatic melanoma. He adds that this has never happened before in melanoma because only two years ago there was no drug that was shown to improve survival in patients. He says physicians now have choices. While the drugs still need to be improved, they are a start and something that can be built upon in terms of combination therapies.

Dr. Chapman From Memorial Sloan-Kettering Cancer Center Describes Recent Melanoma Advances

Dr. Chapman Describes Recent Melanoma Advances

Paul Chapman, MD from the Memorial Sloan-Kettering Cancer Center describes the vemurafenib clinical trial.

Dr. Chapman says the vemurafenib trial was a phase III randomized trial for patients with melanoma who had never had prior therapy whose tumors had a mutation in the BRAF gene. These patients were randomized to either receive the experimental drug, vemurafenib, or a standard chemotherapy. Patients were randomized 1:1 and initially no crossover was allowed. The results were that the patients on the vemurafenib arm showed a decreased risk of death of 63%, and as a result the early analysis that showed that decrease led to allowing the patients on the standard chemotherapy drug to crossover to the experimental arm.

Dr. Chapman From Memorial Sloan-Kettering Describes the Vemurafenib Clinical Trial

Dr. Chapman Describes the Vemurafenib Clinical Trial

Paul B. Chapman, MD, from Memorial Sloan-Kettering Cancer Center, describes the most common side effects of the drug vemurafenib (Zelboraf), which includes rashes, joint pain, and inflammation of the liver. He describes that it is very important to be followed closely by a dermatologist while taking the drug because of the possible formation of non-melanoma skin tumors, squamous cell cancer of the skin, and other benign tumors that are easily excised if caught early.

Dr. Paul Chapman from Memorial Sloan-Kettering Cancer Center Describes the Side Effects of Vemurafenib

Paul Chapman, MD

Articles

Dr. Chapman on BRAF/MEK Combination for Melanoma

Dr. Chapman on Vemurafenib Combination Therapies

Dr. Chapman Describes Recent Melanoma Advances

Dr. Chapman Describes the Vemurafenib Clinical Trial

Dr. Chapman Describes the Side Effects of Vemurafenib