gp100 Peptide Vaccine and Interleukin-2 in Patients with Advanced Melanoma

Publication Type
Journal Article
Year of Publication
Schwartzentruber, D; Lawson, D; Richards, J; Conry, R; Miller, D; Treisman, J; Gailani, F; Riley, L; Conlon, K; Pockaj, B; Kendra, K; White, R; Gonzalez, R; Kuzel, T; Curti, B; Leming, P; Whitman, E; Balkissoon, J; Reintgen, D; Kaufman, H; Marincola, F;..
N Engl J Med
Start Page
Date Published
Adult; Antineoplastic Agents; Cancer Vaccines; Disease-Free Survival; Female; Interleukin-2; Male; Melanoma; Middle Aged; Skin Neoplasms; Survival Analysis
{BACKGROUND: Stimulating an immune response against cancer with the use of vaccines remains a challenge. We hypothesized that combining a melanoma vaccine with interleukin-2, an immune activating agent, could improve outcomes. In a previous phase 2 study, patients with metastatic melanoma receiving high-dose interleukin-2 plus the gp100:209-217(210M) peptide vaccine had a higher rate of response than the rate that is expected among patients who are treated with interleukin-2 alone. METHODS: We conducted a randomized, phase 3 trial involving 185 patients at 21 centers. Eligibility criteria included stage IV or locally advanced stage III cutaneous melanoma, expression of HLA*A0201, an absence of brain metastases, and suitability for high-dose interleukin-2 therapy. Patients were randomly assigned to receive interleukin-2 alone (720,000 IU per kilogram of body weight per dose) or gp100:209-217(210M) plus incomplete Freund's adjuvant (Montanide ISA-51) once per cycle, followed by interleukin-2. The primary end point was clinical response. Secondary end points included toxic effects and progression-free survival. RESULTS: The treatment groups were well balanced with respect to baseline characteristics and received a similar amount of interleukin-2 per cycle. The toxic effects were consistent with those expected with interleukin-2 therapy. The vaccine-interleukin-2 group, as compared with the interleukin-2-only group, had a significant improvement in centrally verified overall clinical response (16% vs. 6%