Dr. Chmielowski on the Current Treatment Landscape of Metastatic Melanoma

Bartosz Chmielowski, MD, health sciences clinical professor of medicine, the Division of Hematology-Oncology, Sarcoma and Connective Tissue Medical Oncology, the University of California, Los Angeles (UCLA) Health, discusses the current treatment landscape of metastatic melanoma.

The treatment landscape for patients with melanoma has shifted within recent years, according to Chmielowski, particularly in regard to anti–PD-1–based therapies that have emerged as optimal first-line treatment for the majority of patients diagnosed with melanoma. However, patients can still experience disease progression or never respond to this treatment, Chmielowski says.

The up-front treatment landscape in melanoma became complicated with the emergence of different therapies and combinations. Clinicians must decide if they will treat patients with a single-agent PD-1 checkpoint blockade or with combination therapy, Chmielowski continues. These combination therapies include the use of a anti–PD-1 agent and an anti–CTLA-4 agent with nivolumab (Opdivo) plus ipilimumab (Yervoy), or nivolumab with LAG-3–blocking antibody relatlimab-rmbw (Opdualag). These treatment decisions can already be difficult, and they can become increasingly complicated for patients with BRAF mutations, who can also receive treatment with targeted therapy combinations, Chmielowski adds.

If a patient begins treatment with single-agent nivolumab, subsequent therapies can involve the combination of nivolumab plus ipilimumab or relatlimab, or combination therapy with the BRAF inhibitor dabrafenib (Tafinlar) and the MEK inhibitor trametinib (Mekinist) for patients harboring BRAF mutations. If a patient begins treatment with a combination, they could also switch to another of the aforementioned combinations that have not been used yet, Chmielowski notes.

Although there are several treatment options for patients with metastatic melanoma, there remains an unmet need in the space due to the number of patients who will experience progressive disease, emphasizing the need for new drug development, Chmielowski concludes.