Perioperative Pembrolizumab Demonstrates Long-Term Safety, Efficacy Among Patients With Late-Stage, Resectable Cutaneous Melanoma

According to 5-year follow-up results from a phase 1b study, pembrolizumab in both the neoadjuvant and adjuvant setting is safe and effective among patients with resectable, stage III to IV cutaneous melanoma who have achieved a pathological complete response (pCR). 

“While neoadjuvant immunotherapy for melanoma has shown promising results, the data have been limited by a relatively short follow-up time, with most studies reporting 2-year outcomes,” stated Cimarron E. Sharon, MD, University of Pennsylvania, Philadelphia, Pennsylvania, and coauthors. “The goal of this study was to determine long-term outcomes for stage III [to] IV melanoma patients treated with neoadjuvant and adjuvant programmed cell death receptor 1 (PD-1) inhibition.”

In this trial, 30 patients with stage III to IV cutaneous melanoma were enrolled and received 1 dose of 200 mg neoadjuvant pembrolizumab 3 weeks prior to surgery followed by 1 year of adjuvant pembrolizumab following surgical resection. Primary outcomes of this long-term follow-up analysis included 5-year overall survival (OS), 5-year recurrence free survival (RFS), and patterns of recurrence. 

At a median follow-up of 61.9 months, 8 patients had experienced a major pathological response (MPR) with <10% viable tumor remaining or a pCR with no viable tumor remaining. No deaths occurred among those patients. The rest of the cohort experienced a 5-year OS of 72.8% (P = 0.12). Among patients who experienced a MPR or pCR, 2 out of 8 patients experienced recurrence. Of patients with >10% viable tumor remaining, 8 out of 22 (36%) experienced recurrence. The median time to recurrence was 3.9 years among patients with ≤10% viable tumor remaining, and 0.6 years for patients with >10% viable tumor remaining (P = 0.044).

“The 5-year results from this trial represent the longest follow-up of a single-agent neoadjuvant PD-1 trial to date…These results demonstrate the long-term efficacy of single-agent neoadjuvant/adjuvant PD-1 blockade in patients with a pCR and the importance of long-term follow-up for these patients,” concluded Dr Shannon and coauthors. 

Source:

Sharon CE, Tortorello GN, Ma KL, et al. Long-term outcomes to neoadjuvant pembrolizumab based on pathological response for patients with resectable stage III/IV cutaneous melanoma. Ann Oncol. Published online July 4, 2023. doi: 10.1016/j.annonc.2023.06.006