Intralesional therapy for advanced melanoma: promise and limitation

PURPOSE OF REVIEW: Patients with unresectable, multiple or advanced locally/regionally metastatic stage IIIB/C or stage IV M1a melanoma have a high risk for recurrence, progression and metastasis. The article reviews treatment advances for this population. RECENT FINDINGS: After promising phase 2 results with Allovectin-7 (velimogene aliplasmid), overall survival in a phase 3 study was shorter for Allovectin-7 than for dacarbazine/temozolomide (median 18.8 versus 24.1 months). In a phase 2 trial of intratumoral electroporation of plasmid interleukin-12 among 28 patients with advanced melanoma, the primary endpoint of best overall response rate within 24 weeks of first treatment was 32.2% for objective response and 10.7% for complete response. In the phase 3 OPTiM trial of talimogene laherparepvec, the intralesional agent that is furthest along in clinical testing, the primary endpoint of durable response rate was 16% for talimogene laherparepvec and 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. SUMMARY: Despite advances, many patients will need several lines of therapy. Some will not be eligible for systemic therapy. Their low toxicity, easy administration and likely systemic immune effects make intralesional therapies an attractive option.