Jeffrey S. Weber, MD, PhD
In recent years, advancements in the treatment of patients with metastatic melanoma have proceeded in 2 areas: targeted therapies and immunotherapies. There are now multiple choices in both modalities and, for targeted therapies, the options include dual inhibitor combinations.
Jeffery S. Weber, MD, PhD, recently sat down with OncLive
to discuss treatment considerations for 3 cases of patients with metastatic melanoma. Weber, deputy director of the Laura and Isaac Perlmutter Cancer Center, co-director of the Melanoma Program, and head of Experimental Therapeutics at NYU Langone Medical Center, discussed these cases during a live, case-based peer perspective event.
OncLive: What factors do you consider when determining the optimal frontline treatment for this patient with metastatic melanoma?
: The factors are what the disease burden is and what the pace of the disease is. I think those are the 2 most important factors. With a patient with a BRAF
mutation, the biggest factor would be how much disease do they have at the baseline—their disease burden and their LDH, which is really one and the same—and what is the pace of the disease, how fast is it growing.
How might this patient’s moderate disease burden impact his potential for a response to targeted therapy?
It’s well known from a number of studies, including studies recently presented at the European Society for Medical Oncology (ESMO) meeting, that the LDH burden and the number of sites of disease have a clear impact on your ability to have long-term survival with the use of BRAF/MEK inhibition.
If you look at the slides from the presentation of Carolyn Robert, MD, PhD, if you have a normal LDH and 3 or fewer sites of disease, the survival at 2 to 3 years is greater than 50%, implying that those patients will do very well long term. It may constitute the tail of the curve that we can see with targeted therapy, so those patients will have a prolonged duration of response, which is excellent.
How durable a response to the targeted therapy combination would you anticipate for this patient, based on his LDH level, age, and sites of disease?
A normal LDH patient with a relatively low disease burden—that is, modest disease burden plus a few sites of disease—is a patient who can do very well in the long term. You’re anticipating a response duration of years, with a potential plateau on that survival curve.
What impact have BRAF/MEK inhibitors had on the management of metastatic melanoma since their initial approval in January 2014, and how has this changed practitioner attitudes toward molecular testing of melanoma?
Clearly, it has had a significant impact in prolonging survival where, for all the BRAF
-mutated patient population, we’re talking a median survival of over 2 years. That would be compared with a decade ago when your chemotherapeutic survival was probably no more than 10 months, so that’s a significant increase. It’s also a significant increase over ipilimumab (Yervoy) alone, where you’re talking maybe 15 months, and it’s certainly caused us to routinely, in all patients with stage III and IV disease, test for BRAF
mutations. In most academic centers, there will be a genomic panel that is obtained.
When testing is indicated, which mutations should be assessed?
We always look for BRAF
V600E and BRAF
V600K, we usually look for NRAS
, and often we will look for KIT if it’s mucosal or acral lentiginous melanoma.
If required, what would your second-line therapy be in this patient who received frontline BRAF and MEK inhibitors?
If this is a patient who went on BRAF/MEK inhibitors, usually in a low-burden patient we would go to a PD-1 drug alone.