Archived Policies - Medicine
Melanoma Vaccines are considered experimental, investigational and unproven.
Tumor (or cancer) vaccines are a type of immunotherapy that attempts to stimulate the patient’s own immune system to respond to tumor antigens. Tumor vaccines have been principally investigated as a treatment of melanoma, due to the recognition that melanoma can induce an immune response, and the overall ineffectiveness of chemotherapy. Melanoma vaccines can be generally categorized or prepared in the following ways:
This policy is based on a 2001 TEC Special Report, “Vaccines for the Treatment of Malignant Melanoma.” The purpose of this report was to review the completed, active, or closed phase III trials of melanoma vaccine and to summarize and evaluate the evidence from phase I/II trials of those melanoma vaccines in phase III trials at that time. The report looked separately at evidence on patients with stage II disease (locally advanced), stage III disease (limited nodal metastases), and stage IV disease (advanced regional or distant metastases). The report offered the following observations and conclusions.
Stage II disease
Studies of vaccine in patients with stage II melanoma (localized disease) suggest a benefit for vaccine; however, there are insufficient data to permit conclusions regarding the outcomes of vaccine use in this disease stage. In addition, only historical controls from other studies are available for comparison, and patients' characteristics and non-vaccine treatments were not matched, making valid comparisons difficult. The results of phase III trials of vaccine therapy are necessary to determine whether or not vaccines will benefit stage II and in-transit melanoma patients compared to standard therapy.
Stage III disease
Studies of a variety of vaccines in resected stage III melanoma patients have reported generally favorable survival comparisons to historical outcomes. Resected stage III patients have a low tumor burden, but a poor long-term prognosis, and so might benefit from vaccine therapy. However, improvements in staging and treatment over time make unmatched, historical comparison unreliable for accurate assessment of efficacy. The results of randomized, controlled phase III trials of vaccine therapy are necessary to determine whether or not vaccines will benefit resected stage III melanoma patients compared to standard therapy. Although phase III trials may not show the same degree of benefit for vaccine as phase II trials, vaccines that result in outcomes that equal standard therapy and are significantly less toxic may be an attractive alternative for some patients.
Stage IV disease
Stage IV melanoma patients who can be rendered clinically disease-free by resection may have survival outcomes similar to resected stage III patients and make good candidates for vaccine therapy clinical trials. However, for stage IV patients, with tumors that cannot be completely resected, survival is poor, tumor burden is high, and regimens involving combination chemotherapy or chemoimmunotherapy have not significantly improved survival compared to dacarbazine therapy. Vaccines are unlikely to obtain a significant response, especially as evidence suggests that high tumor burden may induce immunosuppression, and may be more likely to escape immune detection due to tumor heterogeneity developing over time. The results of phase I/II trials in stage IV or stage III–IV patient groups in general appear to be as good as standard therapy but show little added benefit (although vaccine therapy has low toxicity). Response rates and disease-free survival results tend to overlap with those expected for dacarbazine therapy; in some trials, the range of results appears to extend beyond that of dacarbazine. However, it is not possible to know if this represents a true benefit of vaccine therapy or an artifact due to comparison to unmatched, historical controls. The results of phase III trials are needed to determine efficacy for melanoma patients compared to standard therapy.
A literature search was performed for the period of November 2004 through May 2006. At the present time, no melanoma vaccine has received approval from the U.S. Food and Drug Administration (FDA). A search of the clinical trials database reveals several phase III trials, and many phase I and II trials investigating a variety of vaccines, including peptide and dendritic cell vaccines.
The latest analysis of a phase III trial of high-dose interferon versus Melacine® plus low-dose interferon in resected stage III disease indicated similar relapse-free and overall survival with less toxicity in the combination arm. Median overall survivals have not yet been reached. The FDA has announced that it will require a new study for Melacine®, which will take eight to ten years to complete before they will approve Melacine® for commercial use in the United States.
Recently, Antigenics, the manufacturer of Oncophage® (formerly known as HSPPC-96) announced the preliminary results of a phase III trial. The study enrolled 322 patients with stage IV melanoma; patients in the treatment arm had a 50% improvement in the median survival compared to conventionally treated patients. However, this difference is not statistically significant. The result of this trial has not been published in a peer reviewed journal and Oncophage® is not yet FDA approved.
In October 2005 a phase III trial evaluating Canvaxin™ whole cell vaccine in stage IV melanoma was halted due to low likelihood of significant benefit. In light of the disappointing clinical trial data, the company (CancerVax & Serona) abandoned research on a treatment for malignant melanoma.
Each benefit plan, summary plan description or contract defines which services are covered, which services are excluded, and which services are subject to dollar caps or other limitations, conditions or exclusions. Members and their providers have the responsibility for consulting the member's benefit plan, summary plan description or contract to determine if there are any exclusions or other benefit limitations applicable to this service or supply. If there is a discrepancy between a Medical Policy and a member's benefit plan, summary plan description or contract, the benefit plan, summary plan description or contract will govern.
Medicare (CMS) does not have a national position on this service. It is subject to local carrier discretion. Please refer to the local carrier for more information.
The information contained in this section is for informational purposes only. HCSC makes no representation as to the accuracy of this information. It is not to be used for claims adjudication for HCSC plans.
Vaccines for the Treatment of Malignant Melanoma. Chicago, Illinois: Blue Cross Blue Shield Association – Technology Evaluation Center Assessment Program (2001 May) 16(4): 1-45.
Hsueh, E.C., Essner, R., et al. Prolonged survival after complete resection of disseminated melanoma and active immunotherapy with a therapeutic cancer vaccine. Journal of Clinical Oncology (2002) 20(23):4549-54.
Mitchell, M.S., Abrams, J., et al. Interim analysis of a phase III stratified randomized trial of melamine + low-dose intron-a versus high-dose intron-a for resected stage III melanoma. Chicago, Illinois. American Society of Clinical Oncology (ASCO) Annual Meeting (2003 May 31-June 3) Abstract 2851.
Suckow, M.A., Wolter, W.R., et al. Prevention of de novo prostate cancer by immunization with tumor-derived vaccines. Cancer Immunology, Immunotherapy (2005 January) 54(6): 571-6.
Melanoma Vaccines. Chicago, Illinois: Blue Cross Blue Shield Association Medical Policy Reference Manual (2005 February) Medicine 2.03.04.
Paczesny, S., Shi, H., et al. Measuring melanoma-specific cytotoxic T lymphocytes elicited by dendritic cell vaccines with a tumor inhibition assay in vitro. Journal of Immunotherapy (2005 March-April) 28(2): 148-57.
Spaner, D.E., Hammond, C., et al. A phase I/II trial of oxidized autologous tumor vaccines during the 51watch and wait51 phase of chronic lymphocytic leukemia. Cancer Immunology, Immunotherapy (2005 July) 54(7): 635-46.
Mocellin, S. Cancer vaccines: the challenge of developing an ideal tumor killing system. Frontiers of Bioscience (2005 September 1) 10: 2285-305.
Emens, L.A., and E.M. Jaffee. Leveraging the activity of tumor vaccines with cytotoxic chemotherapy. Cancer Research (2005 September 15) 65(18): 8059-64.
Baxevanis, C.N., Sotiriadou, N.M., et al. Immunogenic HER-2/neu peptides as tumor vaccines. Cancer Immunology, Immunotherapy (2006 January) 55(1): 85-95.
Chen, P.W. and R.R. Keander. Termination of systemic immunity in the presence of intraocular tumors: influence of ocular immune privilege on tumor vaccines. Current Eye Research (2006 January) 31(1): 43-55.
Zhou, G., Drake, C.G., et al. Amplification of tumor-specified regulatory T cells following therapeutic cancer vaccines. Blood (2006 January 15) 107(2): 628-36.
Dolan, B.P., Gibbs, K.D., et al. Tumor-specific CD4+ T cells are activated by 51cross-dressed51 dendritic cells presenting peptide-MHC class II complexes acquired from cell-based cancer vaccines. Journal of Immunology (2006 February 1) 176(3): 1447-55.
Garza, E., and C.Y. Okada. Adjuvant IL-15 does not enhance the efficacy of tumor cell lysate-pulsed dendritic cell vaccines for active immunotherapy of T-cell lymphoma. Cancer Immunology, Immunotherapy (2006 April) 55(4): 420-32.
Hahn, T., Alvares, I., et al. Short-term dietary administration of celecoxib enhances the efficacy of tumor lysate-pulsed dendritic cell vaccines in treating murine breast cancer. International Journal of Cancer (2006 May 1) 118(9): 2220-31.
eMedicine.com - Swetter, Susan M. Malignant Melanoma. November 24, 2005, eMedicine Continuing Education (2006 May) <http://www.emedicine.com>
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