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gp100 Peptide Vaccine and Interleukin-2 in Patients with Advanced Melanoma.
Schwartzentruber, Douglas J. M.D.; Lawson, David H. M.D.; Richards, Jon M. M.D., Ph.D.; Conry, Robert M. M.D.; Miller, Donald M. M.D., Ph.D.; Treisman, Jonathan M.D.; Gailani, Fawaz M.D.; Riley, Lee M.D., Ph.D.; Conlon, Kevin M.D.; Pockaj, Barbara M.D.; Kendra, Kari L. M.D., Ph.D.; White, Richard L. M.D.; Gonzalez, Rene M.D.; Kuzel, Timothy M. M.D.; Curti, Brendan M.D.; Leming, Phillip D. M.D.; Whitman, Eric D. M.D.; Balkissoon, Jai M.D.; Reintgen, Douglas S. M.D.; Kaufman, Howard M.D.; Marincola, Francesco M. M.D.; Merino, Maria J. M.D.; Rosenberg, Steven A. M.D., Ph.D.; Choyke, Peter M.D.; Vena, Don B.S.; Hwu, Patrick M.D.
[Article] New England Journal of Medicine. 364(22):2119-2127, June 2, 2011.

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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%, P=0.03), as well as longer progression-free survival (2.2 months; 95% confidence interval [CI], 1.7 to 3.9 vs. 1.6 months; 95% CI, 1.5 to 1.8; P=0.008). The median overall survival was also longer in the vaccine-interleukin-2 group than in the interleukin-2-only group (17.8 months; 95% CI, 11.9 to 25.8 vs. 11.1 months; 95% CI, 8.7 to 16.3; P=0.06).

CONCLUSIONS: In patients with advanced melanoma, the response rate was higher and progression-free survival longer with vaccine and interleukin-2 than with interleukin-2 alone. (Funded by the National Cancer Institute and others; ClinicalTrials.gov number, NCT00019682.)