Melanoma Immunotherapy: Neoadjuvant Pembrolizumab 71% pCR, Ipilimumab After Anti-PD-1 Limited
A phase 2 trial showed neoadjuvant pembrolizumab achieved a 71% pathological complete response rate in resectable desmoplastic melanoma. A real-world study found ipilimumab monotherapy after anti-PD-1 progression yielded an ORR of 10.8% and median OS of 7.6 months in advanced melanoma.
Two studies reported outcomes for immunotherapy in melanoma. The phase 2 SWOG S1512 trial found that neoadjuvant pembrolizumab achieved a 71% pathological complete response rate (95% CI: 51–87; P<0.001) in patients with surgically resectable desmoplastic melanoma, meeting the prespecified primary endpoint. A retrospective real-world study of ipilimumab monotherapy after progression on anti-PD-1 therapy in advanced melanoma showed an objective response rate of 10.8% and a median overall survival of 7.6 months.
In the SWOG S1512 trial, 28 eligible patients with resectable desmoplastic melanoma received intravenous pembrolizumab at a dose of 200 mg every 3 weeks for three cycles prior to surgical excision. The primary endpoint was the pathological complete response rate by local pathological review. Secondary endpoints included clinical response rate, overall survival, and treatment-related toxicities. At three years of follow up, four participants had died, none attributable to melanoma or treatment-related adverse events. Two patients (7%) experienced grade 3 treatment-related adverse events, with no additional high-grade toxicities reported.
The real-world study included 120 patients with advanced melanoma who had received prior anti-PD-1 monotherapy and subsequently developed disease progression, after which ipilimumab was administered as second-line immunotherapy. The objective response rate was 10.8%, with 1 (0.8%) complete response and 12 (10%) partial responses; 21 (17.5%) achieved stable disease, and 85 (70.8%) had progressive disease. Median progression-free survival was 3 months (95% CI 2.6–3.7), with 6- and 12-month PFS rates of 29.9% and 10.9%. Median overall survival was 7.6 months (95% CI 6.2–10.1), with 1- and 2-year OS rates of 32.39% and 14.01%. Male sex and increased lactate dehydrogenase activity were significantly associated with worse PFS and OS. The study concluded that the real-world efficacy of ipilimumab monotherapy is similar to that reported in clinical trials, with relatively low ORR, PFS, and OS, although a small group of patients benefited from sequential anti-PD-1/anti-CTLA-4 therapy. The study also noted that the nivolumab-ipilimumab combination should be offered as a first-line treatment option in eligible patients.