Single-agent neoadjuvant/adjuvant PD-1 blockade demonstrate long-term efficacy in patients with a complete pathological response

July 11, 2023

Abstract

Background: 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 two-year outcomes. The goal of this study was to determine long-term outcomes for stage III/IV melanoma patients treated with neoadjuvant and adjuvant PD-1 (programmed cell death receptor 1) inhibition.

Patients and Methods: This is a follow-up study of a previously published phase Ib clinical trial of thirty patients with resectable stage III/IV cutaneous melanoma who received one dose of 200mg IV neoadjuvant pembrolizumab three weeks prior to surgical resection, followed by one year of adjuvant pembrolizumab. The primary outcomes were 5-year overall survival (OS), 5-year recurrence-free survival (RFS), and recurrence patterns.

Results: We report updated results at 5 years of follow-up with a median follow-up of 61.9 months. No deaths occurred in patients with a major (MPR, <10% viable tumor) or complete pathological response (pCR, no viable tumor) (n = 8), compared to a 5-year OS of 72.8% for the remainder of the cohort (p = 0.12). Two of eight patients with a pCR or MPR recurred. Of the patients with >10% viable tumor remaining, eight of 22 patients (36%) recurred. Additionally, median time to recurrence was 3.9 years for patients with ≤10% viable tumor and 0.6 years for patients with >10% viable tumor (p = 0.044).

Conclusions: The five-year results from this trial represent the longest follow-up of a single-agent neoadjuvant PD-1 trial to date. Response to neoadjuvant therapy continues to be an important prognosticator with regards to OS and RFS. Additionally, recurrences in patients with pCR occur later and are salvageable, with a 5-year OS of 100%. 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.

Reference:

C.E. Sharon, G.N. Tortorello, K.L. Ma, A.C. Huang, X. Xu, L.R. Giles, S. McGettigan, K. Kreider, L.M. Schuchter, A.J. Mathew, R.K. Amaravadi, P.A. Gimotty, J.T. Miura, G.C. Karakousis, T.C. Mitchell, Long-term outcomes to neoadjuvant pembrolizumab based on pathological response for patients with resectable stage III/IV cutaneous melanoma, Annals of Oncology,
2023, ISSN 0923-7534, https://doi.org/10.1016/j.annonc.2023.06.006.