Jason J. Luke, MD
Experts in the melanoma field are aware of the rapid progress made over the last 5 years, but the explosion of ongoing research—especially with combination regimens—signals that the work is far from done.
For example, in the adjuvant space, the phase III CheckMate-915 trial that is expected to begin recruitment in the future is exploring the PD-1 inhibitor nivolumab (Opdivo) with the CTLA-4 inhibitor ipilimumab (Yervoy) versus nivolumab or ipilimumab alone after complete surgical resection in patients with stage IIIB/C/D to IV melanoma (NCT03068455). This is exploring the potential and safety of the regimen in patients who are at high risk for relapse.
Additionally, there are methods under investigation to bridge the gap between targeted therapies and immunotherapy in melanoma. This year, the community could see data from longer follow-up on patients with melanoma who were given a triplet regimen of a PD-1 antibody plus a BRAF/MEK inhibitor combination, explains Jason J. Luke, MD.
Luke, an assistant professor of Medicine at The University of Chicago Medicine, who also chaired the 2017 OncLive®
State of the Science Summit on Melanoma and Immuno-Oncology, lectured on adjuvant therapy for patients with melanoma, as well as the future of targeted agents and immunotherapy. In an interview during the meeting, he explained these topics a few steps further, sharing what’s next for the ever-evolving field.
OncLive: What is important to highlight regarding adjuvant therapy in melanoma?
Adjuvant therapy for melanoma is becoming more exciting with the approval of ipilimumab a few years ago and, now, the readout of an improvement in OS for patients. We now, for the first time, truly have a drug that improves the overall survival (OS) and outcomes for patients.
That being said, the use of it in standard medical practice is a little complicated. The NCCN still supports observation as opposed to any therapy as a reasonable alternative. Consideration can be given to some patients for observation, while some physicians still advocate the use of interferon, biochemotherapy, and then ipilimumab.
In the study of ipilimumab, it was clear that most of the benefit was derived by the patients who had ulcerated primary lesions or more than 4 lymph nodes that were bad regional melanoma; those are really the patients for whom I prioritize ipilimumab.
It certainly is not the case that all patients should get ipilimumab for stage III melanoma, but rather a discussion should be given about risks and benefits. This is because there is about a one-third chance that a patient will get severe toxicity from ipilimumab, all which is reversible. However, that’s under consideration—especially for patients at a more advanced stage.
Are there other agents being studied in the adjuvant setting?
There is an explosion of clinical trials that are ongoing now. We haven’t had the readouts yet, but clinical trials are going to be coming soon with results. These include comparisons of CTLA-4 blockade with ipilimumab as compared with PD-1 blockade, either with nivolumab or pembrolizumab (Keytruda). The gut feeling is that most oncologists think that those will be positive trials and, given the preferred safety profile of PD-1 antibodies, we’re excited about that to eventually move into the adjuvant setting.
Beyond that, there’s even some discussion around combination immunotherapy with CTLA-4 and PD-1 immunotherapy in the adjuvant setting. That will be a rather toxic adjuvant therapy, so I’m sure there will be much debate about that.