The combination of neoadjuvant and adjuvant pembrolizumab appears more effective than adjuvant pembrolizumab alone for patients with resectable melanoma, according to a phase 2 study presented at ESMO Congress 2022.
“Compared to the same treatment given entirely in the adjuvant setting, neoadjuvant pembrolizumab followed by adjuvant pembrolizumab improves event-free survival in resectable melanoma,” said study presenter Sapna Patel, MD, of the University of Texas MD Anderson Cancer Center in Houston.
“The use of neoadjuvant pembrolizumab did not increase adverse events in the perioperative period,” she added.
Dr Patel and colleagues compared the 2 treatments in the phase 2 SWOG S1801 trial (ClinicalTrials.gov Identifier: NCT03698019). A total of 313 patients with resectable, stage IIIB-IV melanoma were randomly assigned to receive neoadjuvant and adjuvant pembrolizumab (n=154) or adjuvant pembrolizumab alone (n=159).
In the neoadjuvant arm, patients received 3 cycles of pembrolizumab (200 mg IV every 3 weeks) prior to surgery and 15 cycles of pembrolizumab at the same dose after surgery. In the adjuvant arm, patients received 18 cycles of pembrolizumab (200 mg IV every 3 weeks) after surgery. Baseline characteristics were well balanced between the arms.
The primary endpoint was event-free survival (EFS). Events included progression or toxicity that prevented surgery, failure to begin adjuvant therapy within 84 days of surgery, melanoma recurrence after surgery, and death from any cause.
Patient refusal of surgery in the neoadjuvant arm after complete radiographic response was not considered an event, and cancellation of surgery or adjuvant therapy due to site-specific COVID-19-related trial limitations was not considered an event.
Patients in either arm who did not register to adjuvant therapy were assigned an EFS of 84 days, Dr Patel said. She explained that this was done to avoid biasing in favor of the neoadjuvant arm, where the first on-study scan occurred at a later time than in the adjuvant arm and where toxicity from neoadjuvant pembrolizumab could delay a scan.
At a median follow-up of 14.7 months, the median EFS was significantly longer in the neoadjuvant arm than in the adjuvant arm (hazard ratio [HR], 0.58; 95% CI, 0.39-0.87; P =.004). The 24-months EFS rate was 72% in the neoadjuvant arm and 49% in the adjuvant arm.
The EFS benefit with neoadjuvant treatment was consistent across all prespecified subgroups, including by ulceration and BRAF status.
Overall survival data were not mature due to a low number of events (HR, 0.63; 95% CI, 0.32-1.24; P =.18).
Rates of grade 3-4 treatment-related adverse events (TRAEs) were similar between the arms. In the neoadjuvant period, the most common grade 3-4 TRAES were ALT increase (n=3), AST increase (n=2), and hyperglycemia (n=2).
In the adjuvant period, the most common grade 3-4 TRAEs were ALT increase (n=2 in each arm), AST increase (n=2 in each arm), fatigue (n=2 in the adjuvant arm), hyperglycemia (n=2 in the adjuvant arm), lymphocyte count decrease (n=2 in the adjuvant arm, 1 in the neoadjuvant arm), nausea (n=2 in the neoadjuvant arm), pruritus (n=2 in the adjuvant arm, 1 in the neoadjuvant arm), and maculopapular rash (n=4 in the adjuvant arm, 1 in the neoadjuvant arm).
Disclosures: This study was supported by Merck & Co. Some of the study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
Patel S, Othus M, Prieto V, et al. Neoadjvuant versus adjuvant pembrolizumab for resected stage III-IV melanoma (SWOG S1801). Presented at ESMO 2022; September 9-13, 2022. Abstract LBA6.