gp100 Peptide Vaccine and Interleukin-2 in Patients with Advanced Melanoma
06/2011
Journal Article
Authors:
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.;..
Secondary:
N Engl J Med
Volume:
364
Pagination:
2119-2127
URL:
http://www.ncbi.nlm.nih.gov/pubmed/21631324
Keywords:
Adult; Antineoplastic Agents; Cancer Vaccines; Disease-Free Survival; Female; 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%
