What biological therapies are recommended for patients with different types of melanoma?

This article reviewed biological therapies for patients with melanoma based on which type of disease they have.

Patients with melanoma are often treated with surgery to remove tumors first. In some cases, this is not enough. In other cases, patients have inoperable tumors. These patients are offered biological therapies. Biological therapies include BRAF inhibitors, anti-PD-1, and anti-CTLA-4 antibodies. BRAF inhibitors stop the growth of cancer in patients that have BRAF mutations. Commonly used BRAF inhibitors include dabrafenib (Tafinlar), trametinib (Mekinist), encorafenib (Braftovi), binimetinib (Mektovi), vemurafenib (Zelboraf) and cobimetinib (Cotellic).

Cancer often switches the immune system off using molecules PD-1 and CTLA-4. Anti-PD-1 and anti-CTLA-4 are biological therapies that prevent this process and allow the immune system to kill cancer cells. Nivolumab (Opdivo) and pembrolizumab (Keytruda) are commonly used anti-PD-1 drugs. Ipilimumab (Yervoy) is a commonly used anti-CTLA-4 drug. Different patients require different therapies depending on the type, stage or mutation status of melanoma.

Some patients receive biological therapies before getting the main treatment such as surgery. There is no evidence that this improves treatment results for patients with different types of melanoma.

For patients with stage II melanoma that underwent surgery, biological therapies are not required or useful.

For patients with stage III melanoma that underwent surgery, nivolumab or pembrolizumab treatment for 52 weeks can improve results. Ipilimumab and interferon-alpha are not recommended.

Patients with stage III melanoma with V600E/K BRAF mutations (abnormal genes) that underwent surgery are recommended to receive either nivolumab or pembrolizumab or dabrafenib plus trametinib treatment for 52 weeks. For patients with stage III melanoma with non-V600E/K BRAF mutations, it is unclear if dabrafenib plus trametinib treatment is useful.

For patients with stage IV melanoma that underwent surgery, nivolumab treatment is advised.  Pembrolizumab or, for patients with BRAF mutations, dabrafenib plus trametinib treatment may also be useful.

Patients with inoperable or metastatic (cancer that has spread to other organs) melanoma are recommended to receive ipilimumab plus nivolumab followed by nivolumab or nivolumab alone or pembrolizumab alone. This treatment may continue for up to two years. Patients who also have BRAF mutations may additionally be offered dabrafenib plus trametinib or encorafenib plus binimetinib or vemurafenib plus cobimetinib. If patients receiving BRAF inhibitors experience side effects, treatments can be switched. 

For patients who experience cancer worsening while receiving anti-PD-1 drugs, it is advised to switch to ipilimumab or talimogene laherparepvec (T–VEC; Imlygic) which is a virus that kills melanoma cells.  Patients who have BRAF mutations with cancer worsening should switch from BRAF inhibitors to anti-PD-1 or anti-CTLA-4 antibodies. 

Patients with uveal melanoma (of the eye) are recommended to participate in clinical trials where possible. Patients with mucosal melanoma (in the gut, mouth, nose, lungs, bladder or genitals) should follow the above guidelines or participate in clinical trials where possible.

The authors recommended different biological treatments, alone or in combination, based on the type, stage or mutation status of melanoma.