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Updated: Feb 22, 2026
Experimental Melanoma Immunotherapy Model Using Tumor Vaccination with a Hematopoietic Cytokine
Published on: February 24, 2023
Systemic therapy in advanced melanoma: integrating targeted therapy and immunotherapy into clinical practice
Inês P Silva1, Georgina V Long
1aMelanoma Institute Australia, Sydney, Australia bRoyal North Shore, Sydney, Australia cMater Hospital, Sydney, Australia dUniversity of Sydney, Sydney, Australia.
Purpose Of Review:
Here we review the results from relevant phase III trials and discuss treatment strategies for challenging subgroups of melanoma patients.
Recent Findings:
Targeted therapies induce rapid responses in the majority of BRAF-mutant patients, however, 50% of these responders will develop resistance within approximately 13 months. In contrast, inhibitors of checkpoints on T cells, particularly inhibitors of PD-1, induce responses in 40-55% of patients (monotherapy or whenever combined with anti-CTLA-4), and these responses tend to be durable. Data from subgroup analyses of large clinical trials, as well as patient-centred factors, help guide clinicians in their choice of first-line therapy.
Summary:
Immune checkpoint inhibitors and MAP kinase pathway-targeted therapies have revolutionized the management of advanced melanoma, and significantly prolong the overall survival of patients with this disease. The median overall survival is over 2 years for both anti-PD-1-based therapy and combined BRAF and MEK inhibition. Without head-to-head comparison data for either therapy, choice of first-line drug treatment is difficult.
Insights
Advanced melanoma treatment has been revolutionized by immune checkpoint inhibitors and targeted therapies. While both prolong survival, choosing the best first-line treatment remains challenging due to a lack of direct comparison data.
Area of Science:
- Oncology
- Immunology
- Dermatology
Background:
- Advanced melanoma management has been transformed by novel therapeutic agents.
- Understanding treatment resistance and durability is crucial for patient outcomes.
Purpose of the Study:
- To review phase III trial results for advanced melanoma.
- To discuss treatment strategies for challenging patient subgroups.
- To guide first-line therapy selection.
Main Methods:
- Review of relevant phase III clinical trials.
- Analysis of subgroup data from large clinical trials.
- Consideration of patient-centered factors.
Main Results:
- Targeted therapies (e.g., BRAF inhibitors) yield rapid responses but resistance develops in ~50% within 13 months.
- Immune checkpoint inhibitors (e.g., PD-1 inhibitors) show durable responses in 40-55% of patients.
- Both anti-PD-1 therapy and BRAF/MEK inhibition offer median overall survival exceeding 2 years.
Conclusions:
- Immune checkpoint inhibitors and MAP kinase pathway-targeted therapies have significantly improved advanced melanoma survival.
- Durable responses are characteristic of immune checkpoint inhibitors.
- The absence of head-to-head trial data complicates first-line treatment selection.
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