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Real-world data on anti-PD-1 plus lenvatinib as a treatment option in pretreated advanced melanoma patients - a
Lea Jessica Albrecht1, Jana Garnier1, Anne Zaremba1
1Department of Dermatology, University Hospital Essen, Essen and German Cancer Consortium, partner site Essen and National Center for Tumor Diseases (NCT), NCT-West, Campus Essen and University Alliance Ruhr, Research Center One Health, University Duisburg-Essen, Essen, Germany.
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.
Insights
In advanced melanoma patients refractory to prior therapies, the combination of anti-PD-1 and lenvatinib showed meaningful efficacy, particularly in those with BRAF wild-type tumors. This real-world data supports its use when standard treatments are exhausted.
Area of Science:
- Oncology
- Immunotherapy
- Melanoma Research
Background:
- Advanced melanoma patients progressing after immune checkpoint inhibition (ICI) and BRAF/MEK inhibitors face limited treatment options.
- Pembrolizumab plus lenvatinib showed promise in the LEAP-004 trial for PD-1-refractory melanoma.
- Real-world evidence on this combination's efficacy is limited.
Purpose of the Study:
- To evaluate the real-world efficacy and safety of anti-PD-1 plus lenvatinib in heavily pretreated advanced melanoma patients.
- To assess outcomes in patients progressing after standard therapies, including ICI and BRAF/MEK inhibition.
Main Methods:
- Retrospective, multicenter DeCOG study.
- Inclusion of advanced melanoma patients treated with anti-PD-1 plus lenvatinib post-anti-PD-1 failure.
- Data collected from 11 major skin-cancer centers in Germany and Switzerland (Oct 2020 - Mar 2025).
Main Results:
- 120 patients analyzed; median age 59, 70% male, 38% ECOG >1.
- High rates of metastatic sites (69%), brain metastases (42%), and elevated LDH (58%).
- Objective response rate (ORR) 23%, median duration of response 10 months; median PFS 4 months, median OS 10 months. Durable response seen in 23% with mPFS of 21 months. Grade ≥3 AEs in 21%.
Conclusions:
- Anti-PD-1 plus lenvatinib demonstrated meaningful efficacy in a subset of heavily pretreated melanoma patients.
- Efficacy was more pronounced in patients with BRAF wild-type melanoma.
- This combination represents a viable option for patients who have exhausted approved therapies.
