Table 1.
Approved targeted, antibody and other immunotherapies and combination treatments for malignant melanoma.
| Drug | Target | Mechanism | Indication | Approval |
|---|---|---|---|---|
| MONOCLONAL ANTIBODY MONOTHERAPIES | ||||
| Ipilimumab | CTLA-4 | Human IgG1 monoclonal antibody blockade | Advanced unresectable metastatic melanoma | 2011 |
| Nivolumab | PD-1 | Human IgG4 monoclonal antibody blockade | Advanced metastatic melanoma ± refractory to ipilimumab | 2014* |
| *2017: Approved as adjuvant treatment for melanoma with involvement of lymph nodes or for patients with metastatic disease who have undergone complete resection | ||||
| Pembrolizumab | PD-1 | Humanized IgG4 monoclonal antibody blockade | Unresectable melanoma—stage III/IV | 2014 |
| COMBINED MONOCLONAL ANTIBODY THERAPIES | ||||
| Ipilimumab + nivolumab | CTLA-4 + PD-1 | Monoclonal antibody blockade | Unresectable melanoma—stage III/IV PD-L1 negative | 2015 |
| TYROSINE KINASE INHIBITOR MONOTHERAPIES | ||||
| Vemurafenib | BRAF | BRAF inhibitor causing programmed cell death via interruption of MAPK pathway | Unresectable BRAFV600 mutant melanoma | 2011 |
| Dabrafenib | BRAF inhibitor | BRAF inhibitor causing programmed cell death via interruption of MAPK pathway | Unresectable BRAFV600 mutant melanoma (not wild-type) | 2013 |
| Trametinib | MEK inhibitor | MEK1 and 2 inhibitor causing cell death via interruption of MAPK pathway | Unresectable BRAFV600E/K mutant melanoma (not to be used post BRAF inhibitor) | 2013 |
| COMBINED TYROSINE KINASE INHIBITOR THERAPIES | ||||
| Dabrafenib + trametinib | BRAF + MEK | BRAF+MEK inhibition | Unresectable BRAFV600E/K mutant melanoma | 2013 |
| Vemurafenib + cobimetinib | BRAF + MEK | BRAF+MEK inhibition | BRAFV600 mutant melanoma | 2015** |
| **2018: Approved as adjuvant treatment for patients with nodal involvement and following complete resection | ||||
| OTHER TARGETED AND IMMUNE THERAPIES | ||||
| Interferon | IFNα2b | Systemic IFNα2b administration results in immunostimulatory effects including an increase in tumor-infiltration, decrease in circulating T-regs and modulation of STAT1/STAT3 balance | Adjuvant therapy for stage III melanoma (cancer free but at high risk of recurrence) Adjuvant therapy for stage IIB or IIC melanoma with primary lesions >4mm thickness | 1995 |
| Aldesleukin | IL-2 | Systemic IL-2 administration promotes T cell proliferation and stimulates CD8 and NK cell cytotoxicity | Metastatic melanoma | 1998 |
| T-VEC | Oncolytic herpes simplex virus | Local and direct infection and killing of tumor cells | Unresectable stage IIIB, IIIC or IV melanoma | 2015 |