Reinhard Dummer, MD, of University Hospital Zurich, discusses the results of the phase III COMBI-AD study presented at the 2017 ESMO Congress in patients with stage III 

This is a prospective randomized placebo-controlled trial of 900 enrolled patients who had previously undergone complete resection of all metastatic disease. They were then randomized to receive the combination of dabrafenib (Tafinlar) and trametinib (Mekinist) or placebo. The treatment duration was 1 year and the primary endpoint was relapse-free survival (RFS).

There was a clear advantage for the combination over placebo, Dummer explains. The hazard ratio was below 0.5. Other endpoints, aside from RFS, were positive, including distant metastases-free survival and overall survival.  

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Reinhard Dummer, MD, of University Hospital Zurich, discusses the results of the phase III COMBI-AD study presented at the 2017 ESMO Congress in patients with stage III BRAF-mutant melanoma.

Dr. Dummer on COMBI-AD Trial Results in BRAF-Mutant Melanoma

Reinhard Dummer, MD, professor, Department of Dermatology, University of Zurich Hospital, discusses driver mutations and next steps in the treatment of patients with melanoma.

There are several melanoma subtypes based on driver mutations in the MAP kinase pathway. Most of them are mutated for BRAF, and while there are several medications for those types of mutations, there is a huge medical need for specific treatments of NRAS mutations, says Dummer.

The NEMO trial, which randomly assigned patients to receive the combination of the MEK inhibitor binimetinib and dacarbazine or dacarbazine alone, demonstrated binimetinib's potential as an alternative treatment option for patients with NRAS-mutant melanoma. This is a good first step in this setting, says Dummer, but there is certainly room for improved outcomes in future studies.

Dr. Dummer on Driver Mutations and Next Steps in Melanoma

Reinhard Dummer, MD, professor, Department of Dermatology, University of Zurich Hospital, discusses the toxicities of binimetinib in patients with NRAS-mutant metastatic melanoma.

Binimetinib results in many of the same toxicities as other MEK inhibitors, said Dummer. In the NEMO trial, which compared the efficacy of binimetinib with dacarbazine in patients with 

-mutant metastatic melanoma, most adverse were mild and manageable, he said.

However side effects do occur with binimetinib, including muscular toxicities that are reflected by an elevation by the muscle enzyme CPK.

There are also some skin toxicities that result in patients getting an acne-like rash, which is not dangerous, but can be very unpleasant for patients, said Dummer.

Other side effects include gastrointestinal symptoms, such as nausea and diarrhea, but with some additional medications and dose interruption, it can be managed, he said. However, in a number of patients, treatment had to be discontinued due to these adverse events in the NEMO trial.

Dr. Reinhard Dummer on Toxicities with Binimetinib in Metastatic Melanoma

Reinhard Dummer, MD, professor, Department of Dermatology, University of Zurich Hospital, discusses the results of the phase III NEMO trial, which compared the efficacy of binimetinib with dacarbazine in patients with 

In the study, patients were randomized to receive the combination of the MEK inhibitor binimetinib and dacarbazine or dacarbazine alone. The combination arm demonstrated a significant improvement in progression-free survival (PFS), with a hazard ratio of 0.62, Dummer explains.

In a separate analysis that examined the efficacy of the combination in patients who were previously treated with an immunotherapy agent, the benefit was higher than in the overall patient population. In these patients, the median progression-free survival was 5.5 months versus 1.6 months with the combination and dacarbazine alone, respectively.

These findings demonstrate binimetinib's potential as an alternative treatment options for patients with 

View more from the 2016 ASCO Annual Meeting

Reinhard Dummer, MD, professor, Department of Dermatology, University of Zurich Hospital, discusses the results of the phase III NEMO trial, which compared the efficacy of binimetinib with dacarbazine in patients with NRAS-mutant metastatic melanoma.

Reinhard Dummer, MD

Articles

Dr. Dummer on COMBI-AD Trial Results in BRAF-Mutant Melanoma

Dr. Dummer on Driver Mutations and Next Steps in Melanoma

Dr. Reinhard Dummer on Toxicities with Binimetinib in Metastatic Melanoma

Dr. Dummer on NEMO Trial for NRAS-Mutant Melanoma