Velimogene aliplasmid inferior to chemotherapy in advanced melanoma

Patients with recurrent metastatic melanoma treated with velimogene aliplasmid demonstrated inferior response and shorter OS than patients treated with dacarbazine or temozolomide, according to results of an international phase 3 study presented at the Society for Melanoma Research 2013 Congress.

Sanjiv S. Agarwala, MD, chief of hematology/oncology at St. Luke’s Hospital in Bethlehem, Pa., and a HemOnc Today Editorial Board member, and colleagues randomly assigned 390 patients in a 2:1 ratio to treatment with velimogene aliplasmid (Allovectin, Vical Inc.) or chemotherapy.

Sanjiv S. Agarwala

Patients assigned velimogene aliplasmid — a plasmid DNA-based immunotherapy that encodes HLA-B7 and 2-microglobulin — received six weekly 2-mg/dose intralesional injections in a single lesion followed by a 2-week observation period in 8-week cycles.

Patients assigned chemotherapy received 1,000 mg/m2 dacarbazine every 28 days or 150 mg/m2 to 200 mg/m2 temozolomide (Temodar, Schering-Plough) daily for 5 days in cycles repeated every 28 days.

Overall response at 24 weeks served as the primary endpoint. Median OS served as the secondary endpoint.

Patients treated with velimogene aliplasmid achieved a lower overall response rate (4.6%; 95% CI, 2.4-7.9) than patients assigned to the chemotherapy arm (12.3%; 95% CI, 7.2-19.2).

Patients assigned velimogene aliplasmid achieved a median OS of 18.6 months (95% CI, 16.6-21.3), which was inferior to but not statistically different from the 24.1-month (95% CI, 17.1-27.9) median OS in the chemotherapy arm (P=.491).

The most common adverse events observed in patients treated with velimogene aliplasmid were fatigue (33.6%), injection site pain (32%), pyrexia (26.6%), chills (24.3%), nausea (18.5%), headache (18.1%) and extremity pain (15.1%).

Nausea (50%), fatigue (37.5%), vomiting (21.7%), diarrhea (16.7%) and decreased appetite (16.7%) were the most common adverse events in the chemotherapy arm.

Twenty-five of the adverse events observed in the velimogene aliplasmid arm were serious; however, none were deemed related to treatment. Nine of 15 serious adverse events in the chemotherapy arm were related to treatment.

Time to discontinuation due to an adverse events was shorter in the chemotherapy arm (HR=0.229; 95% CI, 0.069-0.764).

For more information:

Agarwala SS. Plasmid DNA-based immunotherapy for metastatic melanoma: A phase 3 trial of velimogene aliplasmid. Presented at: Society for Melanoma Research 2013 Congress; Nov. 17-20, 2013; Philadelphia.

Disclosure: See the study for a full list of the researchers’ relevant financial disclosures.