Melissa A. Wilson, MD, PhD
Exciting long-term findings on the BRAF/MEK inhibitor combination of dabrafenib (Tafinlar) plus trametinib (Mekinist) as treatment for patients with metastatic BRAFV600
-mutant melanoma were presented at the 2017 ASCO Annual Meeting, showcasing the impressive 4- and 5-year overall survival (OS) rates for patients.
In the open-label trial, patients with BRAFV600-mutant melanoma were randomized 1:1:1 to receive dabrafenib (150 mg twice daily) alone, with 1 mg daily of trametinib, or with 2 mg daily of trametinib (n = 54 each).
The data showed that OS with dabrafenib/trametinib continued to remain superior to dabrafenib monotherapy, with 4-year and 5-year OS rates of 30% and 28%, respectively. The progression-free survival (PFS) curve for dabrafenib/trametinib also remained stable, with 4-year and 5-year rates both at 13%. At the 5-year landmark, 1 additional patient who received dabrafenib/trametinib went from a partial response to a complete response.
“We know that targeted therapy can have results in 3 days. We physically see patients changing in 3 days after receiving targeted therapy and feeling better a couple days later. We definitely know that using combinations—a BRAF and MEK inhibitor—really provides improved PFS and OS for patients,” said Melissa A. Wilson, MD, PhD.
In an interview during the 2017 OncLive®
State of the Science SummitTM
on Melanoma and Immuno-Oncology, Wilson, an assistant professor of medicine at Perlmutter Cancer Center at NYU Langone Medical Center, discussed the promising results with BRAF/MEK inhibitor combinations and what ongoing studies have the potential to alter the landscape again.
OncLive®: You lectured on targeted therapies in melanoma. Can you provide some highlights?
: I talked about targeted therapy in melanoma and the origin of targeted therapy, particularly talking about BRAF
-mutant melanoma and BRAF targets, and the success that we have had with these targeted therapies. It has really changed the landscape since 2011 when ipilimumab (Yervoy) and vemurafenib (Zelboraf) were FDA approved, and since then we have identified combination therapy—so BRAF plus MEK inhibitors—and we have seen a number of successes with this combination, including increased PFS, as well as OS, and so we have updated data that demonstrates that there are patients who have longer-term responses, so increased OS at 2 and 3 years, as well.
At the 2017 ASCO Annual Meeting, we saw the 5-year follow-up data of dabrafenib/trametinib and the potential it has in patients with brain metastases. Can you comment?
The 5-year OS data really points to the fact that patients are staying on these treatments a lot longer than we initially anticipated. The thought was that the median PFS was 11.4 months in the trial, so to have 5-year data is really important to demonstrate that there are patients who are still on these targeted therapies. Our concern was that patients are going to develop resistance, so it is showing that a select population still has continued benefit using these.
In the incidence of brain metastases, it is an unmet need still in the field of melanoma. We are doing a great job at controlling systemic disease, but we are seeing a number of patients actually recur with brain metastases. Some of the data show that we are able to use targeted therapy to treat brain metastases. That is actually really promising as well—something to offer patients.
How do you decide which BRAF/MEK combination to use in BRAF-mutant patients?
It is really the side effect profile. While all of the BRAF/MEK inhibitors have very similar general side effect profiles, some of them have little differences and nuances. Dabrafenib/trametinib is associated with pyrexia and the fevers that go along with it. Those are the unique characteristics of that combination.
Whereas, vemurafenib combined with cobimetinib (Cotellic) has photosensitivity associated with it. You could choose 1 regimen over the other depending on patients’ lifestyle and depending on whether patients are outside often or not.