gp100 peptide vaccine and interleukin-2 in patients with advanced melanoma.
2011 Jun 02
Journal Article
Authors:
Schwartzentruber, D.J.;
Lawson, D.H.;
Richards, J.M.;
Conry, R.M.;
Miller, D.M.;
Treisman, J.;
Gailani, F.;
Riley, L.;
Conlon, K.;
Pockaj, B.;
Kendra, K.L.;
White, R.L.;
Gonzalez, R.;
Kuzel, T.M.;
Curti, B.;
Leming, P.D.;
Whitman, E.D.;
Balkissoon, J.;
Reintgen, D.S.;
Kaufman, H.;
Marincola, F.M.;
Merino, M.J.;
Rosenberg, S.A.;
Choyke, P.;
Vena, D.;
Hwu, P.
Secondary:
N Engl J Med
Volume:
364
Pagination:
2119-27
Issue:
22
PMID:
21631324
Keywords:
Adult; Antineoplastic Agents; Cancer Vaccines; Disease-Free Survival; Female; Humans; Interleukin-2; Male; Melanoma; Middle Aged; Skin Neoplasms; Survival Analysis
Abstract:
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.).
