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PD-1 and PD-L1 inhibitors in melanoma treatment: past success, present application and future challenges
Jenny Lee1,2,3, Richard Kefford1,2,3,4, Matteo Carlino1,2,3,4
1Crown Princess Mary Cancer Centre, Westmead hospital, Westmead, NSW 2145, Australia.
Abstract:
Anti-programmed death (PD)-1 antibodies have now become the standard of care for advanced melanoma, with two drugs gaining US FDA approval in recent years: nivolumab and pembrolizumab. Both have demonstrated significant activity and durable response with a manageable toxicity profile. Despite initial success, ongoing challenges include patient selection and predictors of response, innate resistance and optimizing combination strategies. In this overview, we take a closer look at the history and development of therapeutic targets to the PD-1/PD-ligand (L)1 pathway, clinical evidence, availability of biomarkers and their limitations in clinical practice and future strategies to improve treatment outcomes.
Insights
Anti-programmed death (PD)-1 antibodies like nivolumab and pembrolizumab are standard melanoma treatments. Challenges remain in patient selection, resistance, and combination strategies for improved outcomes.
Area of Science:
- Immunology
- Oncology
- Pharmacology
Background:
- Anti-programmed death (PD)-1 antibodies represent a significant advancement in treating advanced melanoma.
- Nivolumab and pembrolizumab are FDA-approved PD-1 inhibitors demonstrating efficacy and manageable toxicity.
Purpose of the Study:
- To review the history and development of PD-1/PD-ligand (L)1 pathway therapeutics.
- To examine clinical evidence, biomarker utility, and limitations in melanoma treatment.
- To explore future strategies for optimizing PD-1-based therapies.
Main Methods:
- Literature review of PD-1/PD-L1 pathway inhibitors in melanoma.
- Analysis of clinical trial data for nivolumab and pembrolizumab.
- Evaluation of current biomarkers and their clinical applicability.
Main Results:
- PD-1 antibodies have established a new standard of care with durable responses.
- Significant challenges persist, including patient stratification and innate resistance.
- Biomarker limitations hinder precise patient selection in clinical practice.
Conclusions:
- Further research is needed to overcome resistance and refine combination therapies.
- Developing robust biomarkers is crucial for personalized treatment selection.
- Optimizing PD-1-based strategies holds promise for improving advanced melanoma outcomes.
