Treatment with neoadjuvant pembrolizumab in patients with resectable desmoplastic melanoma associated with a high pathologic complete response (pCR) rate with excellent tolerability, according to findings of a phase 2 trial presented at the 2022 ASCO Annual Meeting.
Investigators sought to determine the efficacy of neoadjuvant monotherapy targeting programmed death 1 (PD-1) for inducing pathologically confirmed disease regression in desmoplastic melanoma, which could allow for less extensive local treatment (ClinicalTrials.gov Identifier: NCT02775851).
The study population included patients aged 18 years and older who had histologically confirmed desmoplastic melanoma that was resectable (primary, recurrent, or metastatic to regional lymph nodes) with clinical evidence of residual disease. All patients received intravenous pembrolizumab 200 mg every 3 weeks for 3 cycles, followed by excision.
The primary endpoint was pCR rate, with a predefined rate of 25% needed for the study result to be considered positive and worthy of future research.
Secondary endpoints included overall response rate to preoperative therapy, median overall survival, and safety and tolerability of neoadjuvant pembrolizumab.
A total of 29 patients (median age, 75 years; 76% male; 97% White) were included, 1 of whom declined surgery. The primary disease sites were the head and neck (69%), extremities (17%), torso (10%), and unknown (3%); 79% of patients had primary disease, 17% had recurrent disease, and 3% had unknown disease status. None had previously received systemic therapy.
The mean time from start of pembrolizumab therapy to surgery was 81 days (range, 52-135), and the mean number of cycles was 3 (range, 1-4). Overall, 27 patients (93%) had wide excision of resectable disease, 18 with sentinel lymph node biopsy and 3 with lymph node dissection. Also, 1 patient had resection of a nodal recurrence and did not require wide excision.
A pCR was observed in 16 patients (55%; 95% CI, 36%-74%; P <.001), meeting the study’s primary endpoint of a pCR rate of at least 25%. When compared with rates in other cutaneous melanomas, this pCR rate suggests desmoplastic melanoma may be uniquely sensitive to neoadjuvant immunotherapy, according to the investigators.
Of the 13 patients (45%) who did not have a pCR, 1 had residual disease measuring 0.2 mm and 1 chose not to have resection after a clinical CR.
The overall response rate at 9 weeks was 46% (95% CI, 27-67). With follow-up of up to 42 months, the median overall survival duration had not been reached.
Overall, 72% of the cohort had a treatment-related adverse event of any grade, with fatigue (38%) and maculopapular rash (21%) predominating. Two patients (7%) had grade 3 events (1 case of mucositis and 1 case of colitis).
Disclosure: This research was supported in part by Merck Sharp & Dohme LLC. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
Kendra KL, Moon J, Eroglu Z, et al. Neoadjuvant PD-1 blockade in patients with resectable desmoplastic melanoma (SWOG 1512). Presented at ASCO 2022; June 3-7, 2022. Abstract 9502.