We designed the SWOG S1801 study which was for resectable stage 3 or stage 4 melanoma patients. They were randomised 1:1 to receive either three doses of neoadjuvant or preoperative pembrolizumab followed by surgery and then 15 doses of adjuvant pembrolizumab, or surgery up front followed by 18 doses of pembrolizumab. Participants in both study arms received the same surgery and the same number of doses of pembrolizumab.
At ESMO 2023 I presented updated results on the pathologic response. This was performed by central pathologic review. What we found was we were able to obtain samples in 78% of the patients who underwent surgery on the neoadjuvant arm. This was reviewed by a central pathologist who was blinded to clinical results. We had a 38% pathologic complete response rate and 15% pathologic near complete response rate for a collective major pathologic response rate of 53%. The two year recurrence free survival, which is measured from the time of surgery, is 88% in those with the major pathologic response.
We also looked by RECIST response, recognising that most oncologists have radiographic scans more readily available than detailed pathologic response of their melanoma specimen. So, using RECIST response rates we had a 50% objective response rate with 11% of patients having a complete RECIST response and 39% of patients having a partial RECIST response. The two-year progression free survival of those groups are 93% in RECIST complete responders and 92% in RECIST partial responders.
We have now established with the S1801 trial the efficacy of neoadjuvant/adjuvant pembrolizumab and the benefit of giving that treatment over adjuvant pembrolizumab alone. What we discovered this year is that there might be a biomarker to suggest those patients who will have better outcomes. That means either pathologic response or radiographic response. These patients have a better two-year recurrence free survival.