Emerging Therapies for Malignant Melanoma

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There is a lot of excitement over oncolytic viruses, such as talimogene laherparepvec (T-VEC), which can be injected intralesionally to activate a local immune response to the tumor, but also to distant lesions, says Robert Andtbacka, MD. T-VEC is engineered from inactivated herpes simplex 1 and works locally by secreting granulocyte-macrophage colony-stimulating factor (GM-CSF) into the cancer cell. GM-CSF induces an immune response, which in turn generates a more widespread immune response that affects distant disease sites.

In the phase III OPTiM study, T-VEC significantly extended the primary endpoint of durable response rate (DRR) compared with GM-CSF. The DRR was 16.3% with T-VEC and 2.1% with GM-CSF (odds ratio = 8.9; P <.001). The immunotherapy also improved overall survival by 4.4 months; however, the difference was not statistically significant (P = .051).

Another interesting oncolytic agent now in phase I and II trials is CAVATAK, which uses Coxsackievirus Type A21 to target cancer cells, and HF10, notes Andtbacka. Overall, oncolytic viruses are well tolerated, and can be used as monotherapy or in combination with other agents. There may be a role for T-VEC in stage IIIb/c or IV M1a tumors or in resectable melanomas.

For patients with advanced melanoma, combining ipilimumab or PD-1 antibody with an oncolytic virus will likely be more effective, Howard Kaufman, MD, adds. In addition to the idea of combining local and systemic therapies, another very exciting area is the multitude of immune checkpoint inhibitors, adds Richard Joseph, MD. It will be interesting to see how they work as single agents and in combination with other drugs, says Joseph.

In addition to the immunotherapies, antibody-drug conjugates are demonstrating promise in melanoma, and can deliver a toxic agent to the cancer cell itself while minimizing the systemic effects, says Anna Pavlick, DO. This may be a solution for patients with BRAF wild-type tumors who don’t respond to the immunotherapies, she continues. Additionally, Omid Hamid, MD, is excited about the potential for using adoptive T-cell therapies in melanoma. These approaches use autologous cells with an immunostimulant, such as interleukin-2.

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