Jeffrey Weber, MD, PhD
If mature data from the ongoing phase III trial of pembrolizumab (Keytruda) combined with epacadostat are positive, the combination could become the preferred frontline treatment regimen for patients with melanoma, says Jeffrey Weber, MD, PhD.
The ongoing KEYNOTE-252/ECHO-301 study is exploring the efficacy, safety, and tolerability of the PD-1 inhibitor pembrolizumab with the first-in-class IDO1 inhibitor epacadostat in patients with stage III/IV unresectable or metastatic melanoma (NCT02752074).
Findings of the multi-arm, open-label phase I/II ECHO-204 trial of pembrolizumab/epacadostat in patients with advanced solid tumors presented at the 2017 ASCO Annual Meeting showed the combination demonstrated an objective response rate (ORR) of 63% and a complete response (CR) rate of 5% for patients with treatment-naïve melanoma. Based on the projected 2-year survival data, the combination could represent a new, less toxic frontline standard of care for patients with melanoma, said Weber, a medical oncologist and deputy director of the Laura and Isaac Perlmutter Cancer Center at NYU Langone Medical Center.
“The 1- and 2-year survivals are projected to be as good as ipilimumab (Yervoy)/nivolumab (Opdivo), which means a 64% 2-year survival rate,” Weber said. “Let's say it's around a 62% 2-year survival rate. Given the very favorable toxicity profile, a lot of doctors will want to use pembrolizumab/epacadostat in the frontline setting.”
Weber gave a lecture on the past, present, and future landscape of immunotherapy in the field of melanoma at the 2017 OncLive®
State of the Science SummitTM
on Melanoma and Immuno-Oncology. In an interview during the meeting, Weber discussed the combination of nivolumab and ipilimumab for the treatment of brain metastases, the tolerability of the combination of ipilimumab and talimogene laherparepvec (Imlygic; T-VEC), and what is next on the horizon for pembrolizumab.
OncLive®: Can you give an overview of your talk on immunotherapy in melanoma?
: I went over the history of melanoma immunotherapy, not from the very beginnings, but from the beginning of the modern era, where we understood what a checkpoint was and how you inhibit a checkpoint with an antibody, and then I went over some of the initial data. I won’t spend a lot of time on the old data, because there is so much interesting stuff, especially at the recent ASCO meeting. I decided I would put in some of the classic stuff showing the results from trials that led to the approval of pembrolizumab and nivolumab, and not harp much on the really old stuff with ipilimumab from back in 2010 and 2011.
I spent time talking about the updated data from ASCO, which are very interesting—looking at new combinations, activity in brain metastases, long-term outcomes, and new adjuvant data—a whole host of different presentations that I thought would be of interest to the practicing doctor, because that is our audience. My talk had a compendium of data, virtually all of which will have important implications for how they practice, in my view.
Can you discuss the combination of nivolumab and ipilimumab for patients with brain metastases?
That was a very interesting study. That was the initial results from the Bristol-Myers Squibb CA209-204 study. It was essentially a phase II study that was in 2 parts. The data that were presented at ASCO described 75 patients from what they called part A, which were the patients who previously had not received treatment for their brain metastases and were not on steroids.
The results were pretty impressive in that, in the brain, you could get as high of a response rate as you could extracranially, meaning outside the brain. The complete response rate in the brain, and in some cases with some pretty big tumors, was 20%, and that is not bad. It's at least as good as you would see with systemic disease and there was no real disparity between the systemic response, that is the extracranial response, and the response on the brain.
The very impressive data suggest that, in some selected patients with small volume or individual brain metastases, you could start treatment with just ipilimumab plus nivolumab, and you may not need to radiate the metastases. However, relatively few patients will present with isolated single metastases. My personal feeling is that given that stereotactic radiosurgery for subcentimeter lesions is very successful at causing total eradication of those lesions.
I would generally treat first with stereotactic radiosurgery for oligometastatic disease in the brain, and then I would treat with ipilimumab plus nivolumab. It also supports the idea in the relatively unusual patient with central nervous system-only disease, where a patient might have 3 brain metastases, you radiate them, and then what do you do?