Novel Immunotherapy Vaccine Decreases Recurrence in HER2-Positive Breast Cancer Patients


Key Points

  • Patients treated with the GP2 vaccine plus granulocyte-macrophage colony-stimulating factor (GM-CSF) had a disease-free survival rate of 88% vs 81% for those receiving GM-CSF alone, a 37% reduction in recurrence.
  • After excluding patients who did not complete the vaccine series, treatment with GP2 resulted in a 57% risk reduction.
  • Women with the highest overexpression of HER2 had no cancer recurrences when they were administered the vaccine after completing trastuzumab treatment.

A new breast cancer vaccine candidate, GP2, provides further evidence of the potential of immunotherapy in preventing disease recurrence. This is especially the case for high-risk patients when it is combined with a powerful immunotherapy drug. These findings were presented at the 2014 Breast Cancer Symposium in San Francisco (Abstract 134)

One of only a few vaccines of its kind in development, GP2 has been shown to be safe and effective for breast cancer patients, reducing recurrence rates by 57%. Further, women with the highest overexpression of HER2 (known as HER2 +3) had no cancer recurrences when they were administered the vaccine after completing trastuzumab (Herceptin), a type of immunotherapy drug known as a monoclonal antibody. HER2 is an oncoprotein that promotes tumor growth and is expressed to some extent in 75% to 80% of breast cancers.

“This is an important and different avenue in immunotherapy research, in that we are investigating ways to prevent cancer recurrence by stimulating the immune system to treat cancer,” said principal investigator Elizabeth Mittendorf, MD, PhD, Associate Professor of Surgical Oncology at The University of Texas MD Anderson Cancer Center in Houston. “The ultimate goal is to develop a preventative tool that will minimize the risk of recurrence in women who have already had breast cancer and for whom standard therapies have failed.”

Phase II Study

The findings are the result of a phase II randomized trial that paired the GP2 vaccine, designed to stimulate the CD8-positive cells, with an immune stimulant known as granulocyte-macrophage colony-stimulating factor (GM-CSF, Leukine). The trial included 190 patients with varying levels of HER2; 89 women received the GP2 vaccine with a GM-CSF adjuvant and a control group of 91 patients received GM-CSF alone. Eight patients experienced early recurrence or developed a second malignancy and did not complete the vaccine trial.

The vaccine is injected subcutaneously and the initial series consisted of monthly inoculations for 6 months, followed by four cycles of booster shots administered every 6 months thereafter. The patients were monitored for nearly 3 years.

For all 190 patients, including those who did not complete the trial, the disease-free survival rate was 88% among those who received the vaccine and 81% in the control group, a 37% reduction in recurrence. After excluding the patients who did not complete the vaccine series, the disease-free survival rates were higher: 94% vs 85% who did not receive GP2, a 57% risk reduction.

Women with HER2 +3 who were administered trastuzumab 1as part of the standard of care prior to receiving the vaccine experienced no cases of cancer recurrence. According to Dr. Mittendorf, trastuzumab may act like a primer for the vaccine. Trastuzumab stimulates CD4-positive T cells to release substances that fight cancer cells and initiates an antibody response. Thus, it may prepare the immune system, making the vaccine even more effective. Researchers at MD Anderson are now testing this combination of immunotherapies in other clinical trials.

Personalized Immunotherapy

The GP2 study supports previous MD Anderson research on similar breast cancer vaccines, such as AE37, which showed a significant immune response and improved recurrence rates in triple-negative breast cancer patients. Another candidate, E75, known as NeuVax or nelipepimut-S, showed a 50% recurrence decrease in high-risk patients. Currently, NeuVax is being tested internationally in a phase III clinical trial.

“We believe many more patients will benefit in some way from immunotherapy,” said Dr. Mittendorf. “The challenge will be identifying the right immunotherapeutic approach for each individual patient. When doctors are able to do that, cancer therapy, and immunotherapy specifically, will follow a more personalized approach.”

Dr. Mittendorf reported honoraria from Galena Biopharma and institutional research funding from Antigen Express and Galena Biopharma. George Earl Peoples, MD, reported a consultant or advisory role with Norwell.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.