Guidelines for treatment of patients with metastatic melanoma

This study reviewed the updated NCCN guidelines for the treatment of metastatic (spread to other parts of the body) melanoma.

New treatments have been developed in recent years for metastatic melanoma, particularly targeted and immunotherapies. These treatments are leading to improved response and survival in these patients. Recently, the National Comprehensive Cancer Network (NCCN) gathered a panel of experts to update the treatment guidelines to include the use of these new treatment options.

This article reviews these guidelines and updated recommendations for the treatment of to treat metastatic and/or inoperable melanoma.

Checkpoint immunotherapy is a novel treatment that helps the immune system to attack and kill cancer cells. Pembrolizumab (Keytruda) is an immunotherapy. It improves tumor response and progression-free survival (PFS; time from treatment to cancer progression) compared to chemotherapy or ipilimumab (Yervoy) alone. It also leads to fewer side effects.

Nivolumab (Opdivo) blocks the PD1 receptor, which is involved in cancer cell growth. Nivolumab improved response rate, PFS and overall survival (OS, time from treatment until death from any cause) compared to chemotherapy alone. Nivolumab was associated with long-term survival in 50% of patients in one study, with fewer side effects than chemotherapy. It was also more effective than ipilimumab alone.

The combination of nivolumab and ipilimumab improved response and PFS when compared to ipilimumab alone in patients with inoperable stage 3 or 4 melanoma. This combination also improved outcomes in patients with BRAF mutated (a permanent genetic change) tumors. These melanomas tend to be more aggressive. Vemurafenib (Zelboraf) and dabrafenib (Tanfilar) are treatments that target the BRAF mutation. These have been shown to improve response rates, PFS and OS compared with chemotherapy alone in patients with BRAF mutations.

Some patients may become resistant to BRAF inhibitors. This is due to the reactivation of the MAPK pathway (allows the growth of the tumor). Adding an MAPK inhibitor to the treatment can help to overcome BRAF resistance. Examples of MAPK inhibitors are trametinib (Mekinist) or cobimetinib (Cotellic). Combined treatment with dabrafenib and trametinib was shown to improve response rate, PFS, and OS. Treatment with vemurafenib and cobimetinib improved response and PFS compared to vemurafenib alone.

For first-line treatment of advanced melanoma, the recommended treatment options are immunotherapy, BRAF inhibitors or participation in clinical trials. The immunotherapy options are pembrolizumab, nivolumab, or the nivolumab/ipilimumab combination. Treatment decisions should be based on the overall health of the patient and their ability to tolerate side effects.

For patients with BRAF tumors the recommended treatment options are the combination of dabrafenib and trametinib or the combination vemurafenib/cobimetinib. Dabrafenib or vemurafenib alone are also safe treatment options.

For patients whose tumor progress on first-line treatment, options for second-line treatment depend on prognosis. For patients with a poor prognosis, best supportive care should be offered. Patients with better prognosis have several options depending on their BRAF status and treatment history. In addition to the recommended first-line treatment agents, ipilimumab is also an option for these patients. It is recommended that patients receive different therapies for second-line treatment than they did initially.

These NCCN guidelines are updated recommendations for the treatment of patients with inoperable or metastatic melanoma.