Dr Jeffrey Weber discusses adjuvant and neoadjuvant therapy in melanoma.
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TRANSCRIPT
Hello. I'm Dr Jeffrey Weber. I'm a medical oncologist at the Laura and Isaac Perlmutter Cancer Center at NYU Langone Health in New York City. Today, I'll be reporting on a couple of abstracts related to adjuvant and neoadjuvant therapy in melanoma. Also, I'm going to cite, very briefly, a recent publication that also talks about neoadjuvant therapy, which is a coming thing in the treatment of melanoma and many other cancers like lung, head and neck, and renal cancer.

Sapna Patel presented the first abstract, and it was a followup on some very nice work from the SWOG 1801 trial, which was a clinical trial in which patients in a phase 2 style were randomly allocated to receive either neoadjuvant pembrolizumab times three cycles, then surgery, then adjuvant pembrolizumab, or just go straight to surgery and then have adjuvant pembrolizumab.

Adjuvant pembrolizumab, of course, is standardofcare, FDAapproved therapy in resected stage III melanoma. All patients in that original trial, SWOG 1801, had clinically detected disease either radiologically or palpably. At 2 years, the eventfree survival was 72% vs 49%, which is a very impressive difference, with a P value of .004 and a hazard ratio of 0.58.

The presentation made at the 2023 European Society for Medical Oncology (ESMO) meeting showed that the concordance in the pathologic assessment was pretty close to 90%. In the real world you're going to have individual institutions doing pathologic assessment of neoadjuvant specimens — which I think, as has become evident over the past couple of years, is clearly prognostic for outcome.

The recurrencefree survival by pathologic response was also assessed in this trial. You had a very nice 87%89% 2year recurrencefree survival if you had a pathologic complete response (CR), a 90% CR, or 50% pathologic CR. If it was a past nonresponse, meaning 50%, those patients did not do as well, and their recurrencefree survival was about 70% at 2 years.

Again, if you look at major pathologic response — meaning ≥ 90% necrosis up to 100% vs not having a major pathologic response — there was a clear difference, at 88% to 2 years vs 80% in terms of eventfree survival.

Interestingly, if you look at the actual Response Evaluation Criteria in Solid Tumors (RECIST) response on CT scans before and at the time of surgery, that's actually about 50%, whereas the actual pathologic response rates are somewhat higher. If you look at the recurrencefree survival by RECIST response, there is a clear association. The patients who have a CR do the best. The patients who have progressive disease or no change are the ones who do the worst at 24 months.

What do we know? A significant portion of the specimens from this large, randomized phase 2 cooperative group trial — I think it was 73% of the specimens — were looked at, and the concordance was very good with central pathology and individual institutions. The major pathologic response rate was 53%, which I think is quite respectable. There's no question that at 2 years, both eventfree and recurrencefree survival are segregated by RECIST response and by pathologic response.

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