In exploratory analyses of results from the SWOG S1801 trial in patients with stage III to IV resectable melanoma, researchers saw a major pathologic response in more than half of surgical specimens taken from patients who had been treated with neoadjuvant pembrolizumab.
These and other results of the analyses were presented as a proffered paper at the European Society of Medical Oncology (ESMO) Congress 2023 by Sapna P. Patel, MD, Chair of the SWOG Melanoma Committee and Associate Professor of Melanoma Medical Oncology at The University of Texas MD Anderson Cancer Center (Abstract LBA48). Dr. Patel is also the principal investigator of the S1801 trial.
“The pathologic responses seen in S1801 highlight the potential for single-drug immunotherapy to achieve results that we know are important for individual patient outcomes, namely the demonstration of a favorable pathologic response after a few doses of treatment,” Dr. Patel said.
Sapna P. Patel, MD
She continued, “But it is important not to overinterpret the results. The absence of a pathologic response means there is room for improvement, but those patients still likely benefitted from a neoadjuvant approach with immunotherapy where their immune system began priming with tumor in situ than if they had gone to upfront surgery. The goal of a short duration of neoadjuvant immunotherapy is to initiate tumor priming, not necessarily to shrink the tumor(s) or demonstrate pathologic response. Even in the absence of a radiographic or pathologic response, a patient’s immune system may have a more amplified and diversified response after a few doses of preoperative immunotherapy, and then the tumor can be resected. Soon, we hope to find regimens that are safe and powerful enough where the extent of surgery may even be reduced or avoided.”
Earlier Results From S1801
Primary results for S1801 were reported the ESMO Congress 2022 and were published in The New England Journal of Medicine in March 2023. They showed that patients with operable stage IIIB through stage IV melanoma who started immunotherapy before surgery had significantly longer event-free survival times than patients who started immunotherapy after their surgery.
Data Presented at the ESMO Congress 2023
The abstract presented at the ESMO Congress 2023 reports results of exploratory analyses of response to neoadjuvant treatment, which was evaluated using specimens removed from these patients during surgery. Specimens were submitted for central review from 78% of patients who underwent surgery in the neoadjuvant arm. “This is considered a huge success for clinical trial tissue submission in the cooperative group setting,” Dr. Patel highlighted. “We are grateful to sites and investigators for their cooperation.”
“Major pathologic response” here is defined as no more than 10% of residual viable tumor in the examined tissue. It encompasses both the complete response and the near-complete response categories.
A total of 135 patients in S1801 who received neoadjuvant pembrolizumab subsequently underwent surgery. From these patients, 105 specimens were submitted for central review for pathologic response; the vast majority of these were lymph node specimens. All reviews were performed by Victor G. Prieto, MD, PhD, the Ferenc and Phyllis Gyorkey Chair for Research and Education in Pathology at The University of Texas MD Anderson Cancer Center. At the time of review, Dr. Prieto had no information on the clinical outcomes associated with each specimen.
“Particularly interesting was the observation that there was different distribution of response to the treatment (amount of necrosis) among different lesions and even different areas in the same patient,” Dr. Prieto said. “This suggests the existence of different tumor phenotypes in the same patient.”
The research team also correlated pathologic response with recurrence-free survival. They found the rate of recurrence-free survival at 24 months appeared to segregate by pathologic response, and was 89% for patients whose tumor(s) achieved a pathologic complete response.
Disclosure: SWOG S1801 is supported by the National Cancer Institute (NCI), part of the National Institutes of Health (NIH), led by the SWOG Cancer Research Network, and conducted by the NIH-funded NCI National Clinical Trials Network (NCTN). It was also supported in part by Merck & Co, Inc, through a Cooperative Research and Development Agreement with the NCI. For full disclosures of the study authors, visit cslide.ctimeetingtech.com/esmo2023.
