Advances in the Treatment of Malignant Melanoma - Episode 4

pCR and Neoadjuvant Therapy for Melanoma

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Jeffrey S. Weber, MD, PhD: Speaking of practice changing, let’s get back to the neoadjuvant sphere, where there could be some things that will change practice. Do you utilize an assessment, like a pathologic complete response, to determine how you will subsequently treat an adjuvant patient? Let’s say they get neoadjuvant off-protocol or on-protocol ipilimumab-nivolumab, then they have a pCR [pathologic complete response]. What does that tell you? How does that impact your treatment?

Sunandana Chandra, MD: That’s an excellent question. One of the things we’re trying to answer in our field of melanoma is if pathologic complete responses or near-complete responses will actually translate to survival benefit, just like in our breast cancer population? There’s been some unique retrospective and prospective studies that are certainly intriguing and I think require further study in this patient population. For example, Dr Alex Menzies last year discussed a retrospective pooled analysis. I believe it was 6 neoadjuvant trials—well, it was a combination of neoadjuvant and adjuvant. It was a very heterogeneous patient population. The patients were treated with targeted therapy as well as immunotherapy. Even in the immunotherapy cohort, some were treated with anti–PD-1 alone, some with anti–PD-1 and CTLA4 alone. Looking at these in a pooled analysis is challenging to draw conclusions from; however, I think we learned some important things from the retrospective data. I believe the pathologic response rate was about 41%, in terms of complete responses. We learned that with targeted therapies, you can get rapid responses; however, with the combination of ipilimumab-nivolumab, the response rates in terms of pathologic complete responses seem to be higher. The data were retrospective, so we need to keep that in mind.

More recently, this year, Dr [Christian] Blank discussed the OpACIN-neo trial. In that trial, it was around 114 patients. They were studied with 3 dosing schemas of anti-CTLA4 and anti–PD-1, settling on ipilimumab 1 mg/kg plus nivolumab 3 mg/kg for 2 cycles, and that showed a pretty favorable pathologic response rate of about 77%. Interestingly, the grade 3/4 AEs [adverse events] were pretty tolerable, at only about 20%.

Some big questions are about the number of cycles needed. We don’t know, but it certainly is quite intriguing. What I found the most interesting about the trial is that the investigators looked at whether therapeutic lymph node dissections could be omitted for some patients. Patients with a complete pathologic response or a near-pathologic response actually were omitted from a further therapeutic lymph node dissection. I believe 70 of 99 patients achieved a pathologic response in what was noted as their indexed lymph node. Once there was a pathologic response in the indexed lymph node that was significant, those patients did not have to go further—

Jeffrey S. Weber, MD, PhD: Right. That was the PRADO trial. That was Christian’s oral presentation. I thought that was pretty interesting.

Sunandana Chandra, MD: Correct. I think the surgery-related adverse effects were lower in that group. There’s a lot to be further understood about which patients benefit from neoadjuvant trials and which patients actually could potentially skip surgery.

Transcript Edited for Clarity