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Although dermatologists do not typically treat melanoma, we are typically the first step in a patient's care that often involves rigorous interventions. Thus, it is important for us to keep abreast of the latest developments in melanoma therapy and follow any promising leads. Given the deadly nature of the disease, with survival rates estimated at 15 percent over five years,1 treatment success often depends on the stage of disease. While the current output of therapies has not made a significant impact on the overall treatment spectrum, some therapies have been shown to extend survival. These include recently approved agents, such as the targeted therapies vemurafenib, dabrafenib, and trametinib, as well as the immunotherapy ipilimumab.

While newer therapies have been shown to offer some benefit, the future of melanoma treatment could very well hinge on therapies and innovations that have not reached the market yet. Ahead I will assess the potential of some of the agents currently under investigation.


PV-10. One agent that has consistently appeared on news wires is PV-10 from Provectus Pharmaceuticals, a 10% solution of Rose Bengal under investigation for the treatment of locally advanced metastatic melanoma. PV-10 is designed to selectively target and destroy cancer cells without harming surrounding healthy tissue, significantly reducing systemic side effects. In terms of mechanism of action, initial findings suggest that PV-10 is taken up by tumor cells and not normal cells.2 It appears to localize in plasma membranes, nuclear membranes, and lysosomes,2 however the exact mechanism of action is not fully understood.

Preliminary research has shown significant reduction in melanoma lesions in mice. More recently, results from Phase II trials were presented at the recent American Association for Cancer Research (AACR) Annual Meeting in San Diego. The findings showed that best overall response (BORR, judged by modified RECIST) was achieved in 51 percent of patients (26 percent complete response, 25 percent partial response), with the amount of tumor burden accessible to PV-10 injection prognostic for outcome. In patients where all disease was treated (35 percent of patients) BORR further increased to 71 percent, with 50 percent achieving complete response.

Provectus recently submitted an application to the FDA to receive Breakthrough Therapy Designation (BTD). FDA guidelines state that the Agency will make a decision on the application within 60 days of receipt, so a decision is expected soon. Despite promising early findings, it is important to note that mouse data do not always translate to human findings. Forthcoming data will hopefully clarify the relevance of this agent in human patients.

T-vec. Another agent showing promise is T-vec, also known as talimogene laherparepvec, a vaccine that may shrink advanced melanoma tumors. A form of gene therapy, T-vec is an engineered virus that replicates the tumor when injected, destroying cancer cells and priming the immune system to attack cancer cells elsewhere. In a recent Phase 3 trial, T-vec displayed efficacy when compared to standard GM-CSF treatment alone.3,4

In previous Phase I and II clinical trials, the biweekly intratumoral administration of talimogene laherparepvec (formerly known as OncoVEXGM-CSF) to patients with various solid tumors, including unresectable melanoma, was well tolerated.4-6 According to one review, if T-vec is approved, it would become just the second FDA-approved gene therapy product used in standard patient care.3


We still have much to learn about melanoma, from its underlying etiology and pathology, to ideal pathways to treatment. While we cannot foresee the specific benefits that these and other investigational agents may confer, the promise of improved therapies will hopefully continue to grow stronger as we better understand the nuances of this disease.

Jonathan Wolfe, MD is a Clinical Associate Professor of Dermatology at the University of Pennsylvania in Philadelphia, PA. He is also Division Head of Dermatology at Einstein Montgomery Hospital in East Norriton, PA and maintains a private practice in Plymouth Meeting, PA.

  1. Saraceni MM1, Khushalani NI, Jarkowski A. J Pharm Pract. 2014 Mar 27.
  2. Mousavi SH, Zhang XD, Wachter E, Hersey.
  3. Goins WF1, Huang S, Cohen JB, Glorioso JC. Engineering HSV-1 Vectors for Gene Therapy. Methods Mol Biol. 2014
  4. Galluzzi, L, Lugli E. Cancer Immunotherapy turns viral. Oncoimmunology. Apr 1, 2013; 2(4): e24802.
  5. Hu JC, Coffin RS, Davis CJ, Graham NJ, Groves N, Guest PJ, et al. Clin Cancer Res. 2006;12:6737–47.
  6. Senzer NN, et al. J Clin Oncol. 2009; 27: 5763–71.
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