A vaccine for breast cancer

A new vaccine (Neuvax, nelipepimut-S or E75), which can prevent recurrence of early-stage, HER2 medium or low expression breast cancer, is being tested. Currently, since 2011 the vaccine is in a third phase of clinical trials but the preliminary results will be known in 2015. Vaccine is directed against E75 peptide isolated from the protein receptor HER2/neu. The results of the first and second phase of trials indicate reduced recurrence of the cancer than in the control group, lower mortality rate and the absence of bone metastasis in case of recurrence. In the article the way of action, patients’ criteria selection, results of the first and second phase of clinical trials, toxicity as well as perspective of spreading the vaccine, will be presented.

In the United States annually the cancer of breast is detected in about 200 000 women. About 75% of them has a HER 2 receptor-Human Epidermal growth factor Receptor 2 (IHC 1+, 2+ or 3+). In patients with the 3+ receptor subtype we can apply herceptine (trastuzumab). Unfortunately, the majority of the patients has a middle or low expression of this receptor and cannot undergo this therapy. Neuvax was designed for this majority of patients, who had remission after treatment and there were no recurrences.

The vaccine consists of a synthetic peptide E75 isolated from protoonkegene HER2/neu. It is applied together with an adjuvant, which enhance immunogenicity-Leukine (sagramostime, GM-CSF), and water for injection. E75 stimulates cytotoxic T cells (CD8+) of the patient in a specific way and directs them against the cells showing even the slightest level of HER2 expression. The advantage of the vaccine based on a peptide is that it is simple, inexpensive, does not cause side-effects, is safe for the patient, can be easily monitored, and can be produced on a larger scale in the future.

E75 was administered after completion of standard therapy (surgery, radiotherapy and chemotherapy). The vaccine was injected intradermally (four divided doses in the upper part of the thigh), monthly for six months. Booster doses were applied every six months, for a total of 36 months.

Currently, large, randomized trials of the vaccine, which is in the third phase of clinical trials (the first two phases have been successfully completed), are conducted. In the experimental treatment there were involved women aged over 18 years who have been diagnosed (histopathologically) for invasive breast carcinoma. The cancer has already given lymph node metastasis, and the stage was assessed on T1-3. The tumor did not show the presence of the HER2 receptor (described as HER1+ or HER2 +), and the patients had haplotype HLA-A2 or HLA-A3. Before applying the vaccine the tumor mass was excised completely, chemo-and radiotherapy were completed, and the patient did not show any signs of a disease. Women with autoimmune disorders, advanced coronary heart disease, previously receiving Herceptin, with bilateral breast cancer, pre-identified ductal cancer, as well as those using immunosuppressive therapy, were excluded.

Interesting research results, after using the vaccine in the first and the second phase of clinical trials, are presented in an article of prof. Amin. A. et all [1]. The study was conducted on 186 female patients, of which 177 have completed the program. In the control group recurrences occurred in 14.3% , and in the vaccinated group only in 8.3% (p = 0.17). In the vaccinated group 8 recurrences occurred, but they were more advanced and faster spread to the lymph nodes. In the control group, the half of the recurrences gave bone metastasis. After immunization, there were no patients with bone metastasis (p = 0.005). Mortality in the vaccinated group was 12.5%, and 41.7% in the control group.

In the first and the second phase of clinical trials were experienced side effects such as: local erythema, redness, itching and discomfort at the injection site. The most common systemic side effects were: bone pain, flu-like symptoms, headache and muscle pain (but they were short-term and assigned to the administration of GM-CSF). Local and systemic complications were mostly not serious (grade 1 and 2).

Currently, patients for the third phase of clinical trials are being recruited in multiple centers in the United States. This study will evaluate the survival at 3, 5 and 10 years both in the test group and in the control one. Secondary objectives are to assess 3, 5 and 10-year recurrence-free survival, time to local and distant recurrence, as well as time to bone metastasis formation. It is also planned to assess side effects and safety of the vaccine. The results of this study which began in 2011 will be known only in 2022, but preliminary results will be released in May 2015. It is estimated that at the current stage of research about 700 women will participate.

Neuvax is a promising alternative for patients who suffer from breast cancer negative for HER2 receptor. There are strict criteria for classification of the patients for vaccination (the most important criteria are: tumor located only on the one side, at the time of vaccination-cancer in remission, after completing the traditional methods of treatment-surgery, chemotherapy and radiotherapy). The results obtained in 1 and 2 phase of clinical trials are extremely promising and indicate a smaller number of recurrences and lower mortality rate than in the control group. Significant is also the fact that after vaccination when the recurrence appears it does not cause any bone metastasis. However, if the disease after vaccination recurs, the cancer seems to be at the more advanced stage than in the control group. Currently the third phase of clinical trials is conducted and the preliminary results will be known in 2015. The E75 may be a promising method for the prevention of breast cancer recurrences but further investigation is needed. The promising results were also obtained with a combination of Neuvax and Herceptin applied in patients with HER2 positive prostate cancer.

Written by: Magdalena Mroczek

1. Peoples GE, Holmes JP, Hueman MT, Mittendorf EA, Amin A, Khoo S, Dehqanzada ZA, Gurney JM, Woll MM, Ryan GB, Storrer CE, Craig D, Ioannides CG, Ponniah S. Combined clinical trial results of a HER2/neu (E75) vaccine for the prevention of recurrence in high-risk breast cancer patients: United States Military Cancer Institute Clinical Trials Group Study I-01&I-02. Clin Cancer Res 2008;14:797-803.
2. Amin A. et al.(2008) Assessment of immunologic response and recurrence patterns among patients with clinical recurrence after vaccination with a preventive HER2/neu peptide vaccine: from US Military Cancer Institute Clinical Trials Group Study I-01 and I-02 Cancer Immunol Immunother, 57(12), 1817-25.
3. Mittendorf EA, Holmes JP, Ponniah S, Peoples GE. The E75 HER2/neu peptide vaccine. Cancer Immunol Immunoth 2008;57:1511-21.
4. Gates, JD, Carmichael MG, Benavides LC, Holmes JP, Hueman MT, Woll MM, Ioannides CG, Robson CH, McLeod DG, Ponniah S, Peoples GE. Long-term follow-up assessment of a HER2/neu peptide (E75) vaccine for the prevention of recurrence in high-risk prostate cancer patients. J Am Coll Surg 2009;208:193-201.

Would You like to know more? Watch on MEDtube.net: Breast cancer – Histology

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