A new clinical trial from the ECOG-ACRIN Cancer Research Group (ECOG-ACRIN) presented at the European Society for Medical Oncology (ESMO) 2025 Congress found that adjuvant therapy with the PD-1 inhibitor pembrolizumab appeared to reduce the risk of distant metastases for an aggressive form of skin cancer when given immediately after surgery, but did not significantly reduce the overall risk of recurrence, which was a co-primary endpoint of the trial (Abstract LBA56). The randomized phase III STAMP trial (EA6174) is the largest clinical study to date evaluating the immunotherapy vs observation as adjuvant therapy for Merkel cell carcinoma following surgical removal of the tumor.
The STAMP trial found that after 2 years, 73% of patients receiving pembrolizumab showed no cancer recurrence, compared with 66% who were assigned to the observation arm. Although this difference did not reach statistical significance, patients receiving pembrolizumab had a 42% lower risk of developing distant metastases, which was a secondary objective of the study.
“The STAMP trial provides the first evidence that immunotherapy with pembrolizumab after surgery may help people with Merkel cell carcinoma by preventing their cancer from returning in organs considered distant from the site of the original disease,” said lead investigator Janice M. Mehnert, MD, Co-Chair of the ECOG-ACRIN Melanoma Committee and Director of Melanoma and Cutaneous Medical Oncology at NYU Langone Health’s Perlmutter Cancer Center. “This is much-needed good news for people who are living with the highly aggressive cancer that is Merkel cell carcinoma,” Dr. Mehnert added.
Merkel cell carcinoma is a fast-growing cancer that begins in the skin’s sensory cells, often appearing as a single, painless bump on sun-exposed areas. Although skin cancer is by far the most common type of cancer in the United States, Merkel cell carcinoma, also called neuroendocrine carcinoma of the skin, is highly uncommon, occurring in no more than 3 out of 1 million people annually. It is extremely aggressive, with fewer than half of patients surviving 5 years after diagnosis.
More Key Results From STAMP
The phase III multicenter study (ClinicalTrials.gov identifier NCT03712605) was conducted from 2018 to 2023 and involved 293 patients whose tumors had been surgically removed. Of these, 147 were randomly assigned to receive pembrolizumab infusions after surgery, while 146 were observed without additional drug therapy. Some participants also received radiation as advised by their physicians. The median age was 69 years, and about 68% were male. About 85% of patients had stage III disease.
Because Merkel cell carcinoma is a rare tumor, Dr. Mehnert emphasized that national collaboration is essential for recruiting patients for a trial of this scale. Supported by the National Cancer Institute (NCI), ECOG-ACRIN opened the study at over 500 hospitals and cancer centers nationwide, through the NCI’s National Clinical Trials Network.
At final analysis (90 relapse-free survival events), relapse-free survival was numerically higher in the pembrolizumab arm than in the observation arm (42 vs 48 recurrence events, respectively) but not statistically significant (P = .105; hazard ratio [HR] = 0.80, 95% confidence interval [CI] = 0.53–1.22). With a median follow up of 40 months, 1- and 2-year relapse-free survival rates were 83% (90% CI = 78%–89%) and 73% (90% CI = 67%–79%) in the pembrolizumab arm and 71% (90% CI = 65%–78%) and 66% (90% CI = 59%–73%) in the observation arm. Distant metastasis–free survival was significantly higher in the pembrolizumab arm (HR = 0.58, 90% CI = 0.35–0.94, P = .032). Among patients who did not receive adjuvant radiotherapy, relapse-free survival was numerically higher in those who received pembrolizumab (HR = 0.62, 90% CI = 0.37–1.02, P = .056).
Safety events were consistent with the established profile of pembrolizumab. Grade 3 or higher treatment-related events occurred in 31% of patients receiving pembrolizumab and 4% those assigned to observation; one patient in the pembrolizumab group had treatment-related grade 5 pneumonitis.
Overall survival, the other co-primary endpoint of the trial, continues to be followed and will be reported at a later date.
The authors concluded, “In EA6174, the first phase III report of adjuvant immunotherapy in Merkel cell carcinoma, pembrolizumab resulted in a trend toward improved relapse-free survival and significantly prolonged distant metastasis–free survival. Final overall survival data will further inform clinical practice.”
Disclosure: For full disclosures of the study authors, visit cslide.ctimeetingtech.com.
