The Evolution and Impact of Combination Therapies in Treating Stage III and IV Melanoma

By Danélia Botes

October 2, 2023

A New Era in Melanoma Treatment

The landscape of treating stage III and IV malignant melanoma (MM), one of the most aggressive skin cancers, has drastically transformed over the past decade. The introduction of immune checkpoint inhibitors (ICIs) such as ipilimumab (IPI) and nivolumab (NIVO) has revolutionized melanoma treatment, offering increased overall survival rates compared to traditional chemotherapy.

The Rise of Combination Therapies

The development and approval of combination therapies have further enhanced treatment effectiveness. These therapies, which combine two active ingredients in one drug, aim to simplify administration, increase patient adherence, and consequently lower costs. Using a combination of NIVO and IPI as a treatment option, showed improved effectiveness compared to using IPI as monotherapy.

The long-term potential of using combination therapy remains a big topic of debate in the industry. When using fixed combinations there is a limit to adjust individual dose regimens which could potentially reduce efficacy. The safety of combination drugs is also not yet fully understood, and their long-term effects remain to be controversial.

Evaluating Cost-effectiveness

Combination therapies have been proven to be more effective, but they also come with higher costs. Studies have found that NIVO plus IPI is cost-effective in Japan, Canada, and the United States when compared to NIVO, IPI, and pembrolizumab. In Switzerland, however, the combination therapy does not prove to be cost-effective compared to vemurafenib.

The effectiveness of BRAF and MEK inhibitors combination therapy varies. Generally this combination is associated with superiority in terms of progression-free survival, overall survival, and objective response rate compared to monotherapy. This however, will need to be confirmed in terms of the long-term effectiveness and cost-effectiveness of these therapies.

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