SAN ANTONIO – A phase III trial of an adjuvant breast cancer vaccine will begin enrollment before the end of 2011 as a result of favorable 5-year efficacy and safety data in a phase II study.
In updated phase II results, disease-free survival at a median follow-up of 60 months was 95.9% in 53 patients who received the E75 vaccine with multiple booster inoculations, significantly better than the 79.7% figure in 79 controls (P = .016), Dr. Timothy J. Vreeland reported at the San Antonio Breast Cancer Symposium.
Dr. Timothy Vreeland
The vaccine, known as NeuVax, is composed of the E75 peptide, which is derived from human epidermal growth factor receptor 2 (HER2), mixed with granulocyte macrophage colony-stimulating factor (GM-CSF). The vaccine has previously been shown to stimulate cytotoxic T cells to specifically target cells expressing HER2.
As a result of lessons learned in the randomized phase II study, the phase III trial will be restricted to patients with lymph node–positive tumors who are clinically disease-free after completing standard therapy. Only patients with low levels of HER2 expression, meaning immunohistochemistry 1+ or 2+, will be eligible.
The E75 vaccine was initially given as an intradermal injection once a month for 6 months. Because of waning immunity noted during phase I and II testing, however, a booster immunization program was initiated. It consists of a booster injection once every 6 months. The booster program will be routine in the phase III trial.
The overall phase II study population consisted of 187 patients with node-positive or high-risk node-negative tumors expressing any level of HER2. The median 5-year disease-free survival in the 108 patients in the vaccine arm was 89.4%, compared with 79.7% in controls, a nonsignificant difference. But the vaccine arm included 55 women who didn’t receive booster immunizations. When they were excluded, the 5-year disease-free survival rate climbed to 95.9%, according to Dr. Vreeland, a U.S. Army captain at San Antonio Military Medical Center.
The E75 vaccine has been very well tolerated. A total of 70%-85% of local and systemic toxicities in both the primary vaccination series and the booster inoculations have been grade I, with the remainder grade II. Seven of 53 patients (13%) in the booster program developed grade II delayed urticarial reactions at a median of 9 days post inoculation.
The phase III trial is called PRESENT (Prevention of Recurrence in Early-Stage, Node-Positive Breast Cancer with Low to Intermediate HER2 Expression with NeuVax Treatment).
The NeuVax vaccine has been licensed by the U.S. military to Galena Biopharma. Dr. Vreeland declared having no relevant financial disclosures.