Real-world data on anti-PD-1 plus lenvatinib as a treatment option in pretreated advanced melanoma patients - a retrospective DeCOG study
Menée en Allemagne et en Suisse dans un contexte de vie réelle à partir de données portant sur 120 patients atteints d'un mélanome de stade avancé et réfractaire aux anti-PD-1 (durée médiane de suivi : 13,4 mois), cette étude rétrospective évalue l'efficacité, du point de vue du taux de réponse objective, de la survie sans progression et de la survie globale, et la toxicité d'un traitement combinant lenvatinib et anti-PD-1
Background: Patients with advanced melanoma progressing after immune checkpoint inhibition (ICI) and BRAF/MEK inhibition have limited therapeutic options. In the LEAP-004 trial, pembrolizumab plus lenvatinib demonstrated activity in PD-1-refractory melanoma. The combination has emerged as a potential option when approved therapies have been exhausted; however, real-world evidence regarding its efficacy remains limited.
Methods: This retrospective, multicenter DeCOG study included patients with advanced melanoma treated with anti-PD-1 plus lenvatinib after failure of anti-PD-1-based therapy at 11 major skin-cancer centers in Germany and Switzerland between October 2020 and March 2025.
Results: Overall, 120 patients were analyzed (median age 59 years); 70% were male and 38% had an ECOG performance status >1. Most patients had ≥3 metastatic sites (69%), brain metastases (42%), and elevated LDH (58%). Median follow-up was 13.4 months. Patients received a median of two prior systemic therapy lines; 98% had been pretreated with ipilimumab/nivolumab, and 66% exhibited primary resistance to prior ICI. The objective response rate was 23%, with a median duration of response of 10 months; disease control rate was 47%. Median progression-free survival (mPFS) was 4 months and median overall survival (mOS) was 10 months, with 12-month PFS and OS rates of 17% and 42%, respectively. Durable disease control beyond six months was observed in 23% of patients, with mPFS of 21 months. Grade ≥3 treatment-related adverse events occurred in 21% of patients.
Conclusions: In this real-world cohort, anti-PD-1 plus lenvatinib demonstrated meaningful efficacy in a subset of heavily pretreated patients, predominantly in those with BRAF wild-type melanoma.
European Journal of Cancer , résumé, 2026