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A 3D Organotypic Melanoma Spheroid Skin Model
Published on: May 18, 2018
Algorithm for the management of metastatic cutaneous melanoma
Antonio C Buzaid1, Sanjiv S Agarwala2, Axel Hauschild3
1Centro Oncológico Antonio Ermírio de Moraes, São Paulo, Brazil. buzaidac@yahoo.com.br.
Abstract:
Over the last 4 years, various drugs have been approved for the treatment of metastatic cutaneous melanoma. Ipilimumab, an anti-CTLA-4 inhibitor that stimulates antitumor immunity, was the first agent to improve overall survival both in first line and in previously treated patients. Ipilimumab results in long term disease control in approximately 20% of the patients. Vemurafenib was the first BRAF inhibitor (BRAFi) approved and also resulted in improved overall survival compared with dacarbazine in patients with BRAF mutated metastatic melanoma. More recently, another BRAFi, dabrafenib, and a MEK inhibitor, trametinib, were approved either alone or in combination as they each showed significant antitumor activity relative to dacarbazine and the combination appeared superior to dabrafenib monotherapy. The major feature of such tumor targeted therapy is its high response rate (40-70%) and the rapidity of the responses, resulting in prompt clinical improvement. However, unlike immunotherapy, targeted therapy does not result in long-term treatment free survival. In this paper, we discuss how best to integrate the currently available treatment options including high-dose interleukin-2 (HD IL-2), systemic chemotherapy, ipilimumab and tumor targeted therapy in various clinical scenarios.
Insights
New melanoma treatments, including immunotherapy like ipilimumab and targeted therapies (BRAF/MEK inhibitors), offer improved survival and response rates. Integrating these options is key for managing metastatic cutaneous melanoma effectively.
Area of Science:
- Oncology
- Immunology
- Pharmacology
Background:
- Metastatic cutaneous melanoma treatment has advanced significantly with new drug approvals in the last four years.
- Ipilimumab, an anti-CTLA-4 immunotherapy, was the first to improve overall survival and offers long-term disease control in a subset of patients.
- BRAF inhibitors (BRAFi) and MEK inhibitors have demonstrated significant antitumor activity and improved survival in BRAF-mutated melanoma.
Purpose of the Study:
- To review and discuss the integration of newly approved treatments for metastatic cutaneous melanoma.
- To compare the efficacy and long-term outcomes of immunotherapy versus targeted therapy.
- To provide guidance on combining various treatment modalities in different clinical scenarios.
Main Methods:
- Review of recently approved drugs for metastatic cutaneous melanoma.
- Comparison of clinical trial data for ipilimumab, BRAF inhibitors, and MEK inhibitors.
- Discussion of treatment integration strategies based on drug class and patient characteristics.
Main Results:
- Ipilimumab provides long-term disease control in approximately 20% of patients.
- Targeted therapies (BRAFi, MEK inhibitors) show high response rates (40-70%) and rapid clinical improvement.
- Unlike immunotherapy, targeted therapies do not typically result in long-term, treatment-free survival.
Conclusions:
- Effective management of metastatic cutaneous melanoma requires integrating immunotherapy, targeted therapy, chemotherapy, and high-dose interleukin-2.
- The choice of treatment strategy should be tailored to individual patient clinical scenarios.
- Balancing response rates, duration of response, and long-term survival is crucial in treatment planning.
