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

Indiana University Health Goshen Center for Cancer Care, Goshen, IN 46526, USA.
New England Journal of Medicine (Impact Factor: 55.87). 06/2011; 364(22):2119-27. DOI: 10.1056/NEJMoa1012863
Source: PubMed


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.
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.
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).
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.).

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    • "Table 2.2 Spectrum of current vaccine platforms in Phase II/III clinical studies—cont'd Vaccine platform Example Cancer type References Saccharomyces cerevisiae (yeast) Yeast ras Pancreatic Remondo et al. (2009), Wansley et al. (2008) Listeria Listeria mesothelin Pancreatic Singh and Paterson (2006) Alpha-and adenoviruses Adeno-CEA, alpha-CEA Carcinoma MacDonald and Johnston (2000) Peptides/proteins Peptide gp100 (modified), MUC-1 (Stimuvax), HER2/neu Melanoma, lung Disis (2009), Butts et al. (2005), Pejawar-Gaddy et al. (2010), Finn et al. (2011), Schwartzentruber et al. (2011), Sosman et al. (2008), Salazar et al. (2009), Brichard and Lejeune (2008), Disis (2011) "
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