E75 vaccine reduced recurrence, mortality in HER2/neu breast cancer

SAN DIEGO — A HER2 peptide vaccine reduced mortality by 50% in patients with HER2/neu-positive breast cancer, according to the results of a study presented yesterday at the 2008 Annual Meeting of the American Association for Cancer Research.

“E75, if validated in phase-3 testing, may represent a new form of HER2/neu-directed immunotherapy, which could be utilized in the HER2/neu low-expressing group of breast cancer patients — a group of patients for whom immunotherapy has not been available in the past,” Linda C. Benavides, MD, a resident in general surgery at Brooke Army Medical Center, said at an April 13 press briefing.

Benavides presented results from a phase-2 trial of about 200 women with node-positive and node-negative breast cancer. The trial was conducted in the adjuvant setting. Women were clinically disease free and treated with standard multimodality therapy. Ninety-two women underwent vaccination and researchers have now followed them for a median of 30 months.

The mortality rate in women with over-expressing HER2 tumors was 9.1% for the control group vs. 3.4% for the vaccine group. In the low-expressers, mortality was 6.8% for the control group vs. 0% for the vaccine group.

Recurrence rates also decreased with the vaccine. In the over- and low-expresser control groups, recurrence was 18.2%. In the vaccine group, recurrence was 13.8% for over-expressers and 10.7% for low-expressers.

The vaccine also had an effect among patients who had recurrence. In the over-expressers with recurrence, the risk of mortality for the control group was 50% compared with 25% for the vaccine group. For low-expressers who recurred, the risk of mortality was 38% for the control group compared with 0% for the vaccine group.

The vaccine was intradermal, given every three to four weeks for a total of six inoculations. The trial showed that the vaccine is safe with only minimal flu-like symptoms in <20% of women.

Plans for phase-3 trials are in preparation with the FDA. The phase-3 trial for HER2/neu low-expressing patients is proposed to start this fall, Benavides told HemOnc Today. The vaccine has been renamed NeuVax and researchers hope to enroll over 700 women nationally and internationally in about 80 sites. – by Leah Lawrence

The numbers here are very small, but the concept is good. If you can vaccinate against a protein, especially a mutant protein or an over-expressed protein, and you can demonstrate that the body has responded by making T lymphocytes that are now targeting HER2 expressing cells, that is a very important first step. I am being cautiously optimistic.

– William N. Hait, MD, PhD

Immediate Past President, AACR

For more information:

Benavides LC. #2545. Presented at: the 2008 Annual Meeting of the American Association for Cancer Research; April 12-16, 2008; San Diego.