October 2014, Vol 3, No 7

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HER2-Derived Vaccine Cuts Recurrences in High-Risk Breast Cancer

Uncategorized

A vaccine derived from the GP2 peptide was safe and reduced the rate of breast cancer recurrence in women with high-risk breast cancer in a phase 2 clinical trial. The vaccine was particularly effective in reducing recurrence in women with HER2 overexpression, reported Elizabeth Mittendorf, MD, PhD, at the 2014 ASCO Breast Cancer Symposium.

The vaccine is delivered in the adjuvant setting after completion of standard of care therapy, including trastuzumab where appropriate, along with the immunoadjuvant granulocyte-macrophage colony-stimulating factor (GM-CSF) to help stimulate an immune response.

“Peptide vaccines have the benefit of being easy to construct and manufacture on a large scale, they’re inexpensive, and very importantly, they are ‘off the shelf’ therapy,” said Mittendorf, associate professor of surgical oncology at the University of Texas MD Anderson Cancer Center, Houston.

GP2 is a HER2-derived HLA-A2+ restricted immunogenetic peptide designed to stimulate CD8+ cytotoxic T lymphocytes to recognize breast cancer cells with HER2 expression (IHC 1+, 2+, or 3+), said Erika Schneble, DO, coinvestigator and a general surgery resident, San Antonio Military Medical Center.

In the multicenter phase 2 trial, 180 women with HLA-A2+, node-positive or high-risk node-negative breast cancer with any level of HER2 expression rendered disease-free with standard of care therapy were randomized to receive GP2 plus GM-CSF or GM-CSF alone. The vaccine series consisted of 6 monthly intradermal inoculations (primary series) followed by 4 boosters administered every 6 months. HER2 overexpression was present in 57% of vaccinated recipients and 55% of controls.

Only 1 grade 3 local and systemic toxicity was reported in the vaccine group. “The toxicities are mostly grade 1 local and systemic toxicities that match the control arm, suggesting that these toxicities are due to just the immunoadjuvant GM-CSF,” said Schneble. About 70% of patients in each arm had grade 1 local toxicities. Seventy percent in the GM-CSF–alone arm and 60% in the vaccine plus GM-CSF arm had grade 1 systemic toxicity.

Disease-free survival (DFS) was analyzed on an intention-to-treat (ITT) basis and in a population that excluded those who had a recurrence before their primary vaccination series was completed and those who developed a second nonbreast malignancy. Two patients experienced early recurrence and 6 developed a second malignancy.

After a median follow-up of 34 months, the ITT analysis showed a DFS rate of 88% among GP2 vaccine recipients and 81% in the control group, for a nonsignificant 37% relative risk reduction in the vaccine group (P=.428). Excluding the patients who had a recurrence during their primary vaccination series or developed a second malignancy, the DFS rate was 94% in the vaccine recipients versus 85% in the controls, a nonsignificant 57% reduction in risk of recurrence (P=.168).

“After completion of the primary vaccine series, there have been no recurrences in the HER2 3+ population,” said Schneble. “This suggests a possible synergy with trastuzumab. All 3+ patients received trastuzumab as their standard of care therapy.”

Concurrent use of trastuzumab and the GP2 vaccine may address the early recurrences, Mittendorf said. A phase 1 trial of concurrent use showed the combination to be safe, with no increase in local or systemic toxicity. A phase 2 trial looking at combination immunotherapy with trastuzumab and a CD8+ T-cell–eliciting vaccine in high-risk HER2-positive breast cancer will begin enrolling patients.

Uncategorized - October 17, 2014

Novel Treatment-Specific Genetic Marker on the Horizon

One of the areas of personalized medicine that has signaled a new era is the development of genetic signatures that can be used to select therapy that is likely to be effective in separate disease sites: for example, Oncotype DX for breast and colon cancer and MammaPrint for breast cancer. [ Read More ]

Uncategorized - October 17, 2014

Combo of BRAF and MEK Inhibitors Improves Survival in Advanced Melanoma

Combination therapy with a BRAF and a MEK inhibitor improves outcomes in advanced BRAF-positive melanoma, according to 2 phase 3 studies presented at the 2014 ESMO Congress. These studies support the hypothesis that inhibition of both BRAF and MEK will improve survival in melanoma by overcoming the mechanism of acquired [ Read More ]