Expert Perspectives on the Treatment of Melanoma - Episode 1

Melanoma: BRAF Status and a Neoadjuvant Therapy Approach


Sanjiv S. Agarwala, MD: Hello, and thank you for joining this OncLive Peer Exchange® titled “Expert Perspectives on the Treatment of Melanoma.” We have made enormous strides in developing novel therapies for advanced melanoma, particularly in the field of immuno-oncology, where melanoma has been at the forefront of paradigm-defining progress. We continue to see new advances at an accelerated pace as we learn more about the disease itself and how to treat it.

Today I’m joined by a group of international experts in the field of melanoma research. Together we will discuss the studies presented at the 2019 ASCO [American Society of Clinical Oncology] Annual Meeting and will provide you with perspective on how the data relate to clinical practice.

I am Dr Sanjiv Agarwala, a professor of medicine at Lewis Katz School of Medicine at Temple University in Philadelphia, Pennsylvania, and the chief of oncology and hematology at St. Luke’s University Health Network in Bethlehem, Pennsylvania.

Participating today on our distinguished panel are:

Dr Alexander Eggermont, the director general and a professor of oncology at Gustave Roussy in Paris, France.

Dr Caroline Robert, a professor of dermatology and the chairman of the dermatology unit, also at Gustave Roussy.

And Dr Dirk Schadendorf, director of the Department of Dermatology and the West German Cancer Center at the University Hospital Essen, in Essen, Germany.

Thank you so much for joining us. Let us begin.

A lot of data have come out at ASCO recently, so let’s start with the perioperative approaches to melanoma. And let’s start with something different: neoadjuvant therapy. And Dr Eggermont, I’m going to start with you. Is there currently a regulatory path forward for neoadjuvant therapy? Nothing yet approved in that setting. Is there a path forward, thinking about both neoadjuvant immunotherapy and for BRAF-positive patients, targeted therapies?

Alexander Eggermont, MD, PhD: Well, I think there will be a regulatory pathway that needs to be developed because we’re dealing now with no endpoints, which are kind of testy in the sense that whatever regulatory agency you’re discussing, is not used to transforming nonresectable—which is always relatively loosely defined tumors or a lymph node, regional lymph node packages—into resectable tumors and considering whether that is really a reliable endpoint. Then what is going to be your primary endpoint in that setting? Is it going to be the outcome of surgeries? The outcome of pathology? Is it going to be simply relapse rate after all this?

Sanjiv S. Agarwala, MD: For survival?

Alexander Eggermont, MD, PhD: In the end you will need to show that they have benefit on both sides of the equation. It will be a pathway that will be developed because it’s going to be perhaps the revolution in the next 3 to 5 years, not just in melanoma but in multiple tumors.

Sanjiv S. Agarwala, MD: Having said that, in terms of some of the data that have come out, I’d like you to comment perhaps on the ASCO abstract of the pooled analysis of the neoadjuvant melanoma consortium. And then of course there are some data of other meetings of neoadjuvant pembrolizumab, nivolumab-ipilimumab combo, and neoadjuvant BRAF/MEK.

Alexander Eggermont, MD, PhD: For the neoadjuvant situation, when you look at bulky or palpable nodal disease, you can look at BRAF/MEK combos, and you’ll get the immediate response, and you’ll get a good response rate, which is up and above the 70%, 75% in that setting. But it’s limited to BRAF-mutant melanomas. And the trial experience thus far published shows that the impact on relapse-free survival is actually much less than anticipated when you initially look at the response rates and the fact that it may facilitate surgery.

What I think is the untouchable data set right now is the combination of anti—PD-1 [programmed cell death protein 1] plus low-dose ipilimumab. There are no data in advanced disease that can almost not even stand in the shadow of that data when you look at 3-year, 4-year, 5-year survival rates. But it gives very rapid and very impressive responses, and up to 7% pathological complete response [CR] rates in melanoma patients with palpable nodal disease. You can also then see in the Amsterdam trial that there hasn’t been a single patient who has relapsed so far after just 2 cycles of the combination of anti–PD-1 plus low-dose CTLA4. Whether the anti–PD-1 is nivolumab or pembrolizumab doesn’t matter. And when you give low-dose ipilimumab, all patients go to surgery. Nobody fails surgery, and a 70% pathological complete response rate means…

Sanjiv S. Agarwala, MD: Pathological CR rate...

Alexander Eggermont, MD, PhD: This is the new pathway for an approval that will harvest also on the relapse-free-survival equation. I think that’s going to be extremely important.

Transcript Edited for Clarity