Novel vaccine benefitted high-risk patients with HER-2 overexpression

Issue: October 25, 2014

SAN FRANCISCO — A novel vaccine that consists of GP2 and granulocyte-macrophage colony–stimulating factor appeared safe and effective as adjuvant therapy for high-risk patients with breast cancer, according to results of a randomized phase 2 trial presented at the Breast Cancer Symposium.

The combination appeared particularly effective among patients with HER-2 overexpression, a finding that justifies a phase 3 trial designed to evaluate GP2 administered in the adjuvant setting in that patient population, researchers wrote.

“Although immunotherapy has shown initial promise in melanoma and renal cell carcinoma, there is now growing interest in using therapies that stimulate an immune response in other disease sites to include breast cancer,” Elizabeth Ann Mittendorf, MD, PhD, associate professor and deputy chair of research in the department of surgical oncology at The University of Texas MD Anderson Cancer Center, told HemOnc Today. “It is likely that immunotherapy could have a role in treating most cancer patients but, for those of us in the field, we have the responsibility for defining the best immunotherapeutic approach for each disease site and each stage of disease. For breast cancer patients who appear to have responded well to standard therapies but are at risk for recurrence, our group believes that these non-toxic, well-tolerated vaccines may be the right approach.”

GP2 — a HER-2–derived, human leukocyte antigen (HLA) A2 locus-positive–restricted immunogenic peptide — is designed to stimulate CD8-positive T cells to recognize tumor cells with any level of HER-2 expression, according to background information provided by researchers.

Mittendorf and colleagues designed the prospective, multicenter trial to assess whether the addition of GP2 to granulocyte-macrophage colony–stimulating factor (GM-CSF) extended DFS in patients with HLA-A2+ node-positive or high-risk node-negative breast cancer with HER-2 expression who were rendered disease free after standard-of-care therapy, which included trastuzumab (Herceptin, Genentech) when appropriate.

The analysis included 180 patients. Mittendorf and colleagues randomly assigned 89 patients to GP2 plus GM-CSF. The other 91 patients received GM-CSF alone. The cohorts were comparable with regard to age, tumor size and grade, node positivity, ER and PR status, and HER-2 expression (P<.05).

All patients received a primary vaccine series that consisted of six monthly inoculations. They then received four boosters, which were administered 6 months apart.

Researchers used the Kaplan-Meier method to perform statistical analysis for both the intention-to-treat population — which consisted all 180 patients — and the per-treatment group, which excluded patients who either developed a second malignancy or experienced recurrence during the primary vaccine series.

Mittendorf and colleagues also performed a pre-specified subgroup analysis based on HER-2 expression, defined as 3+ on immunohistochemistry or >2.2 on fluorescence in situ hybridization (FISH). Of the 101 participants with HER-2 overexpression, 51 received the combination vaccine and 50 received GM-CSF alone.

Median follow-up was 34 months (range, 1-60). Researchers reported comparable DFS rates between the combination treatment and GM-CSF alone in both the intention-to-treat population (85% vs. 81%, P=.05) and the per-treatment population (94% vs. 85%; P=.17).

Among patients with HER-2 overexpression, DFS rates were higher for the combination vaccine among both the intention-to-treat population (94% vs. 89%; P=.86) and the per-treatment population (100% vs. 89%; P=.08). The lack of recurrences among patients with HER-2 overexpression who received the combination vaccine may be due to its synergism with trastuzumab therapy, Mittendorf and colleagues wrote.

Toxicities were comparable between those who received the combination vaccine and those assigned to GM-CSF alone. Researchers reported one grade 3 local and systemic toxicity reaction in the combination group.

“Overall, we’re very pleased with this phase 2 study because it showed the vaccine to be safe and capable of stimulating an antigen-specific immune response, and it has identified the appropriate patient population and strategy to investigate in subsequent trials — specifically the HER-2 3+ patients who received trastuzumab as part of their standard-of-care therapy before vaccination,” Mittendorf said. “Based on the encouraging results from this study, we have designed a follow-on phase 2 trial looking at trastuzumab plus a CD8-positive, T-cell–eliciting vaccine in high-risk HER-2–positive patients. We have defined ‘high risk’ as those who do not achieve a pathologic complete response to neoadjuvant chemotherapy plus HER-2–targeted therapy, or those who undergo surgery as a first intervention and are found to be node positive.”

For more information:

Schneble EJ. Abstract #134. Presented at: Breast Cancer Symposium; Sept. 4-6, 2014; San Francisco.

Disclosure: The researchers report consultant or advisory roles with Norwell, research funding to their institutions from Antigen Express and Galena Biopharma, and honoraria from Galena Biopharma.