Neoadjuvant Pembrolizumab Is Safe and Effective in Resectable Stage III/IV Melanoma

March 30, 2025

Single-dose neoadjuvant pembrolizumab was safe with no surgical delays and boosted MPR rates in resectable melanoma.

Single-dose neoadjuvant pembrolizumab (Keytruda) proved to be tolerable and practical for the treatment of patients with resectable stage III or IV melanoma, according to data from a study presented during a press briefing ahead of the 2025 Society of Surgical Oncology Annual Meeting.

Data from the study demonstrated that patients who received neoadjuvant pembrolizumab prior to surgery (n = 52) did not experience surgical morbidity at a rate of 71.2%. Patients experienced outpatient or inpatient management at rates of 26.9% and 1.9%, respectively. The median time to the first dose of pembrolizumab was 23 days and most patients were able to initiate adjuvant therapy (98%).

Patients experienced a major pathologic response (MPR) at a cutoff of less than 10% of viable tumor cells at a rate of 21.1%. At a median follow-up of 67 months, the 60-month recurrence free survival (RFS) rate was 50.5%. Patients who experienced a MPR (n = 11) achieved a 60-month RFS rate of 77.8%; those without a MPR (>10% viable tumor cells; n = 41; 78.9%) experienced a 60-month RFS rate of 43.4%. These data corresponded to a 34.4% improvement in the 60-month RFS rate in favor of patients with a MPR. The 60-month overall survival (OS) rates were 100% in the MPR group vs 72.6% in the non-MPR group.

“A single dose of neoadjuvant pembrolizumab is a safe and feasible approach with no delays in surgery and appreciable rates of MPR,” the study authors stated in the press briefing.

The study included patients with resectable stage III or IV melanoma. Eligible patients did not receive prior PD-1 therapy and were treated with 1 dose of pembrolizumab before resection and planned to receive 1 year of adjuvant treatment with the agent.

The perioperative outcomes consisted of time to surgery, time to adjuvant therapy, and 30-day complications. Oncologic outcomes included pathologic response, patterns and treatment of recurrence, RFS, and OS.

At baseline, the median age in the overall study cohort was 65 years (IQR, 56-71). All patients were White and non-Hispanic. Most patients had stage III disease (98.1%) and were male (67.3%). BRAF mutational status was comprised of patients with mutated (40.4%), wild-type (32.7%), or unknown (26.9%) disease. Surgery types consisted of cervical (15.4%), axillary (38.5%), or groin (26.9%) lymph node dissection, as well as parotidectomy (1.9%) and wide local excision of in-transit, satellite, or subcutaneous metastases (17.3%).

Additional data from the study showed that 44.2% of patients experienced disease recurrence. Disease recurrence subtypes consisted of locoregional (47.8%), synchronous (13%), and distant (39.1%). Recurrence was addressed with surgery (39.1%), a change in agent (43.5%), or both (17.4%).

Patients who did not experience a MPR were a median age of 65 years (IQR, 56-71). Most of these patients were male (65.9%) and underwent lymph node dissection (80.5%) for their surgery. BRAF status was wild-type (43.9%), mutant (36.6%), or unknown (19.5%).

Similarly, patients who did achieve a MPR were a median age of 63 years (IQR, 50-67). Most patients were male (72.7%) and received lymph node dissection (90.9%). Patients had BRAF unknown (54.5%), wild-type (27.3%), or mutant (18.2%) disease.

All patients were able to undergo surgery and the median time to surgery was 21 days. Most patients experienced no immune-related adverse effects (irAEs; 96.1%). One patient experienced grade 1 rash and another experienced grade 2 fatigue and transaminitis. There were no grade 3 or 4 irAEs reported.

“Late recurrences [were] observed uncommonly in the MPR group, suggesting the need for long-term follow-up,” the study authors stated in conclusion. “Further work [is] needed to delineate [which patients] benefit from anti–PD-1 monotherapy compared [with] combination approaches.”

Reference

Shafique N, Farooq MS, Mattfield V, et al. Single-dose neoadjuvant pembrolizumab in resectable metastatic melanoma. Presented at: Society of Surgical Oncology Annual Meeting; March 27-29, 2025; Tampa, Florida.