Intralesional Treatment for Metastatic Melanoma

Interest in emerging intralesional therapies is justified by their strong ablative effects, lack of toxicity, and their stimulation of local and systemic immunological responses in melanoma patients, according to a recent study published in Current Opinion in Oncology. It is uncertain currently which agents in development will be clinically significant and evoke systemic effects. However, studies suggest that there may be optimal combinations of intralesional therapy, and it is hoped in the coming months and years, intralesional therapies may benefit a significant number of patients with melanoma. 

The study notes that despite advances, many melanoma patients currently need several lines of therapy. Since some patients are not candidates for systemic therapy, intralesional therapies may be an attractive option due to their low toxicity and easy administration. Author Sanjiv Agarwala, MD, chief of medical oncology and hematology at St. Luke’s Cancer Center in Bethlehem, Pa, and professor of medicine at Temple University School of Medicine in Philadelphia, noted that for decades the standard of care has been dacarbazine chemotherapy and high-dose interleukin (IL-2). However, both drugs are limited in their efficacy and application.

With the advent of agents targeting the MAP-kinase pathway and the discovery of more effective immunologic agents, several new drugs have been approved in the past two years. Among the new approaches, Dr. Agarwala discusses intralesional therapies with agents that may not only shrink the tumor directly, but also stimulate a systemic immune response by modifying the tumor's antigenic milieu.

Intratumoral injection of therapeutic agents is appealing for a host of reasons. There is significant interest now in the first intralesional treatment Bacille Calmette-Guerin (BCG), along with Allovectin-7 (velimogene aliplasmid), plasmid IL-12, talimogene laherparepvec (T-VEC), and Provectus Biopharmaceutical's PV-10, according to the study.

Dr. Agarwala writes that after promising phase II results with Allovectin-7 (velimogene aliplasmid), the median overall survival (OS) in a phase III study was found to be shorter for Allovectin-7 compared to dacarbazine/temozolomide (18.8 vs 24.1 months, respectively). In a phase II trial of intratumoral electroporation of plasmid interleukin-12 among 28 patients with advanced melanoma, the primary endpoint of best overall response rate (ORR) within 24 weeks of first treatment was 32.2% for objective response and 10.7% for complete response. In the phase III OPTiM trial of talimogene laherparepvec, the primary endpoint of durable response rate was found to be 16% for talimogene laherparepvec compared to 2% for granulocyte macrophage colony-stimulating factor. In the PV-10 phase 2 trial among 80 patients with stage III/IV melanoma, the overall response rate was 51%, with a 26% complete response rate. Provectus Biopharmaceuticals, the developer of PV-10, now plans further testing.

Dr. Agarwala states that interest in emerging intralesional therapies is justified by their strong ablative effects, lack of toxicity, and their stimulation of local and systemic immunological responses.  He concludes, “What remains unclear at this early stage of experience with the agents in current development is how clinically significant the evoked systemic effects will be.”