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

作者：Douglas J. Schwartzentruber, David H. Lawson, Jon M. Richards, Robert Martin Conry, Donald Max Miller, Jonathan S. Treisman, Fawaz Gailani, Lee B. Riley, Kevin Christopher Conlon, Barbara A. Pockaj, Kari Lynn Kendra, Richard L. White, Rene C. Gonzalez, Timothy Michael Kuzel, Brendan D. Curti, Phillip D. Leming, Eric D. Whitman, Jai Balkissoon, Douglas S. Reintgen, Howard L. Kaufman, Francesco Maria Marincola, Maria J. Merino, Steven A. Rosenberg, Peter L. Choyke, Don Vena, Patrick Hwu · 发表于：New England Journal of Medicine · 年份：2011 · DOI：10.1056/nejmoa1012863 · 被引用次数：906 · 研究领域：Immunotherapy and Immune Responses、vaccines and immunoinformatics approaches、Cancer Immunotherapy and Biomarkers

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 clini...