Jeffrey Weber, MD, PhD
Immunotherapy continues to work its way through the treatment landscape of melanoma, with ipilimumab (Yervoy), nivolumab (Opdivo), and pembrolizumab (Keytruda) leading the way in combination regimens, as well as other novel agents that are currently in development.
in Melanoma, discussed the future of immunotherapy in the treatment of melanoma.
OncLive: What is the current state of immunotherapy in the melanoma paradigm?
: As we all know, immunotherapy for melanoma has revolutionized how we treat the disease. It started out with the best news, which was the long-term survival data that we had from the original randomized trial of ipilimumab plus nivolumab versus ipilimumab alone versus nivolumab alone. You can't argue with a 58% 3-year survival in the arm that got ipilimumab/nivolumab. If you do a quick calculation, you are looking at a median survival that is 4 years, and maybe even longer—and that is a phenomenal number, better than any trial that has been done. That is an amazing record, and you have to put that up as probably the best track record that we have in a melanoma trial.
What is next for this type of therapy in melanoma?
In the short term, the pembrolizumab/epacadostat versus pembrolizumab/placebo trial will read out its primary endpoint of progression-free survival (PFS) in early 2018, I believe. I have high hopes based on the phase Ib/II data that it will be a positive trial for PFS, because with 60 or 70 patients and a PFS of approximately 12-plus months, I can’t argue with that; that is very impressive. A 53% to 56% response rate would suggest that, at least on the surface, it is just as good as ipilimumab plus nivolumab. And, it has a lot less toxicity. Epacadostat, or the IDO inhibitor, adds virtually nothing to the toxicity of pembrolizumab, which itself is a well-tolerated drug.
In the mid- or long-term future, the LAG-3/nivolumab combination looks very promising, especially in the refractory population, and that is a tough population to treat. I assume that will be pursued in the frontline and the refractory settings. Then, there is that nivolumab trial both in renal cell carcinoma and melanoma, which was reported out at the 2017 Society for Immunotherapy of Cancer (SITC) Annual Meeting. It looks awfully promising. Finally, we get a reasonably tolerated interleukin-2 (IL-2)‒type drug—which is the pegylated IL-2 known as NKTR-214—and that looks pretty good. I would have high hopes in the middle-to-long-term future for that combination.
Will the field start moving toward triplets or even 4-drug regimens?
We are already in triplets. I just got approved for a trial of nivolumab plus ipilimumab at flip doses with an HDAC inhibitor, which looks very promising and interesting when combined with PD-1. It will be even better with ipilimumab plus nivolumab.
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