Dr. Michael Ming discusses current and future treatment possibilities for prolonging survival in patients with early stage malignant melanoma.
Michael Ming, MD, FAAD, is Associate Professor of Dermatology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania
“…for a long period of time, we really didn’t have [melanoma] treatment options that prolonged survival for people with metastatic disease. It’s fairly recent that we have treatment options that impact survival for patients who have melanoma that has spread beyond the skin to other organs,” said Michael Ming, MD, FAAD, who directed the session “The Changing Landscape of Early-Stage Melanoma Management” at the 2022 American Academy of Dermatology (AAD) Annual Meeting.
“In 2011, which was only 11 years ago, we had the first FDA-approved treatment for metastatic melanoma, ipilimumab (Yervoy, Bristol Myers Squibb), that was shown to be effective in prolonging survival as opposed to just shrinking a tumor or making a patient temporarily feel better. Since then, there has been an explosion of options, which is really wonderful.”
According to Dr. Ming, there are a dozen different options available today that can effectively help to prolong survival in the metastatic melanoma population.
“But up until extremely recently, those [treatment options] were only available for patients who already had metastatic disease. In order to receive these treatments, patients had to have a melanoma that had already gone beyond the skin into the lymph nodes or to the visceral organs.”
But, said Dr. Ming, what if we could intervene sooner in patients with melanoma who are at high risk for metastatic disease, before it spreads? Great minds—and a few trials—are currently at work on this, he said.
“One of the first trials that examined the effectiveness of medical intervention for patients who, as far as we know, still have melanoma confined only to the skin, just came out in the fall of 2021.”
The study looked at pembrolizumab (Keytruda, Merck), an immunotherapy FDA-approved since 2014 for patients with metastatic melanoma, in 976 patients. Preliminary, 1-year trial results were presented at the European Society for Medical Oncology (ESMO) Congress in 2021.
“The question is this: [For] patients who are very high risk—patients who are AJCC Stage IIB or IIC (patients who either have melanomas that are more than 2 mm with ulceration or more than 4 mm regardless of whether they have ulceration), if you intervene earlier, will [they] actually do better?”
It’s an important question because those patients with a negative sentinel node procedure and an initial workup that shows no evidence of metastatic disease have about a 10-year survival rate of 80%, which means about 20% of such patients will die over that time span, said Dr. Ming.
“Rather than waiting until we have evidence of a problem, why don’t we see if we can intervene earlier?”
From that 1-year data, researchers found a 7% difference in recurrence-free survival, which was statistically significant, said Dr. Ming.
“So 90% of the people who received pembrolizumab had no recurrence for a year. And 83% of the patients who did not get the medication… had a recurrence.”
Based on these data, the FDA approved pembrolizumab for stage IIB/IIC patients in December 2021, said Dr. Ming.
“That’s a big change because now those patients—who, again, as far as we know after the initial workup don’t have an issue—are eligible for treatment.”
Because there are side effects to consider, prescribing pembrolizumab warrants careful consideration and a discussion with the patient about whether it is the right option for them, said Dr. Ming.
“They should either see an oncologist or a pigmented lesion specialist or somebody who [will] discuss that with them.”
According to Dr. Ming, there are other ongoing trials as well, though he isn’t aware of the release of any preliminary results. One is investigating nivolumab (Opdivo, Bristol Myers Squibb), a similar drug to pembrolizumab, for early intervention of melanoma in high-risk patients. Another explores whether targeted therapy with encorafenib (Braftovi, Pfizer) and binimetinib (Mektovi, Pfizer) would be helpful for patients with disease confined only to the skin.
“There’s also a trial going on at Penn, where I work, which is looking at even an earlier step.”
That step is treating melanoma patients with pembrolizumab prior to a sentinel lymph node procedure, said Dr. Ming.
“The idea is that if they have tumor in the sentinel node at the time they are receiving immunotherapy, then maybe it will prime the immune system in some way. So having the antigen present might actually be helpful in terms of response.”
This trial is also ongoing without preliminary results available yet.
“These three additional trials plus the additional information from that first trial (because again, there’s no actual full manuscript from that trial—it’s still ongoing as well)… will provide us a lot of information. It’s really an exciting time because there are a lot of avenues that are being investigated, and I think the way we think about patients in the Stage IIB/IIC group now compared to the way we’ll think about them five years from now may be very, very different.”