ArticleFrontiers in oncology2024
Immunotherapy after progression to double immunotherapy: pembrolizumab and lenvatinib versus conventional chemotherapy for patients with metastatic melanoma after failure of PD-1/CTLA-4 inhibition.
Article in Frontiers in oncology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers, 1 of them a synthesis that pooled it.
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Who cites it
4 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Advancing immune checkpoint inhibitor rechallenge: key insights into efficacy, safety, and personalized strategies in advanced solid tumors.Frontiers in oncology · 2026Pooled it
- Overlapping Toxicities of Pembrolizumab and Lenvatinib: A Case of Capillary Leak Syndrome with Severe Erythroblastosis.Current oncology (Toronto, Ont.) · 2026Article
- Clinical Outcomes of Lenvatinib-Pembrolizumab in a High-Risk, Dual ICI-Refractory Melanoma Cohort.Clinical Medicine Insights. Oncology · 2026Article
- Overcoming resistance to PD-1 and CTLA-4 blockade mechanisms and therapeutic strategies.Frontiers in immunology · 2025Review
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8 authors.
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Abstract
Background: Programmed cell death 1 receptor (PD-1) inhibition as monotherapy followed by Cytotoxic T-lymphocyte associated protein 4 (CTLA-4) inhibition in case of progression or as upfront double co-inhibition has drastically improved the survival outcomes of metastatic melanoma. Still, many patients develop primary or acquired resistance to both agents, relapse soon, and survive less. For these patients, the therapeutic options are very limited, and for many years, conventional chemotherapy (CC) was the standard of care. Recently, the phase II LEAP-004 trial supported that pembrolizumab/lenvatinib could potentially overcome anti-PD-1/anti-CTLA-4 immunotherapy refractoriness. Materials and methods: In the absence of any prospective comparative study and to evaluate in a real-world context the clinical benefit of re-administering a PD-1 inhibitor (pembrolizumab 200 mg i.v. every 3 weeks, Q3W) with a multi-kinase inhibitor (lenvatinib, but at a reduced dose 10 mg p.o. daily due to its known toxicity) in this frail population of unmet need, we conducted here a retrospective comparison of LEAP-004-proposed combination with CC (carboplatin 4 AUC and dacarbazine 850 mg/m Results: A total of 84 patients were included in the effectiveness and safety analysis (pembrolizumab/lenvatinib, n=39 and CC, n=45). The median age was 67 (45-87) years and 64 (34-87) years, and men were 33.3% and 46.7%, respectively. The distribution of their metastatic sites was comparable, including 12.8% and 20% with brain involvement. Most patients had a good PS<2 (69.9% and 56.5%), increased lactate dehydrogenase (LDH) (71.8% and 84.4%), Conclusions: This is the first comparative study in patients with metastatic melanoma refractory to PD-1/CTLA-4 inhibition and showed significantly longer outcomes in cases treated with pembrolizumab/lenvatinib versus CC.
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