Metastatic Melanoma Treatment Options
Treatment for metastatic melanoma often depends on the stage of the cancer. Chemotherapy, for example, which is medication designed to kill cancer cells, is typically not the first line of treatment for melanoma. According to the American Cancer Society, immunotherapy and targeted drugs are generally more effective forms of treatment.
Chemotherapy may be used in advanced cases when other approaches have not worked.
Immunotherapy
Immunotherapy uses the body’s own powerful immune system to treat metastatic melanoma.
One especially promising form of immunotherapy is called immune checkpoint blockade therapy, or immune checkpoint inhibitor therapy. These drugs gained U.S. Food and Drug Administration (FDA) approval in 2011,
and research backs that they are extending the lives of people with stage 3 and stage 4 melanomas. Two forms of immunotherapy drugs, pembrolizumab (Keytruda) and nivolumab (Opdivo), both approved by the FDA in 2014, have become frontline medications for metastatic melanoma. Both work by blocking the action of a molecule called PD-1 (programmed death-1), which normally keeps the immune system’s T cells in check. No longer held back by PD-1, the T cells are let loose to attack cancer.
In 2015, former President Jimmy Carter credited a combination of surgery, radiation, and Keytruda with sending his cancer into full remission after metastatic melanoma had spread to his brain.
In 2021, the FDA approved Keytruda to treat high-risk, stage 2 melanoma.
In 2024, the Annals of Oncology published a 10-year follow-up study to landmark research evaluating pembrolizumab as a treatment for advanced melanoma. It found that the drug was more effective at improving survival rates than another form of immunotherapy, ipilimumab (Yervoy). The results support pembrolizumab’s status as the standard of care for advanced melanoma.
Another viable approach for using immunotherapy to treat metastatic melanoma is to combine checkpoint blockade therapies. Doing so may increase the chance of serious side effects, yet researchers are finding that this strategy can improve survival rates to such an extent that it’s a valuable option for some patients, despite the risks involved.
A study of patients with advanced melanoma who were treated with both nivolumab and ipilimumab (Yervoy) found that after 10 years, the median overall survival for patients on the combined treatment was about six years, while the median overall survival for taking nivolumab alone was about three years and ipilimumab alone was about 1.5 years. Another combination immunotherapy, of nivolumab and relatlimab, has shown promising survival rates for patients with metastatic cancer compared with nivolumab alone.
The FDA recently approved the combination of vusolimogene oderparepvec-wtpg (Tudriqev) and nivolumab to treat unresectable advanced cutaneous melanoma with disease progression that includes a programmed death receptor-1 (PD-1)-blocking antibody-based regimen. Anti-PD-1 refractory melanoma is an advanced form that doesn’t respond to immunotherapy. Rather than a form of immunotherapy, Tudriqev is a genetically modified oncolytic viral therapy. In a clinical trial, 1 in 4 patients responded to the combination.
Targeted Therapies
A new generation of melanoma therapies works by targeting mutations (DNA defects) in melanoma cells, shrinking tumors or slowing their growth.
About one-half of all melanomas have mutations (DNA defects) in the BRAF gene that are responsible for out-of-control cellular growth.
Several medicines targeting this mutation, called BRAF inhibitors, are FDA-approved, with research supporting them as a second line of treatment after immunotherapy.
A combination of these drugs with other drugs aimed at the related MEK mutation to treat metastatic melanoma with the BRAF mutation.
These three combination therapies are now approved:
- dabrafenib (Tafinlar) and trametinib (Mekinist)
- vemurafenib (Zelboraf) and cobimetinib (Cotellic)
- encorafenib (Braftovi) and binimetinib (Mektovi)
