gp100 peptide vaccine and interleukin-2 in patients with advanced melanoma.

Publication Type
Journal Article
Year of Publication
Schwartzentruber, Douglas J; Lawson, David H; Richards, Jon M; Conry, Robert M; Miller, Donald M; Treisman, Jonathan; Gailani, Fawaz; Riley, Lee; Conlon, Kevin; Pockaj, Barbara; Kendra, Kari L; White, Richard L; Gonzalez, Rene; Kuzel, Timothy M; Curti, Brendan; Leming, Phillip D; Whitman, Eric D; Balkissoon, Jai; Reintgen, Douglas S; Kaufman, Howard; Marincola, Francesco M; Merino, Maria J; Rosenberg, Steven A; Choyke, Peter; Vena, Don; Hwu, Patrick
N Engl J Med
Date Published
2011 Jun 02
Adult; Antineoplastic Agents; Cancer Vaccines; Disease-Free Survival; Female; Humans; 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%, 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; number, NCT00019682.).