Monogram Presents Three Studies at The 45th ASCO Meeting Describing HERmark's Ability to Select Trastuzumab Responders and Non-Responders
Studies Highlight the Ability of VeraTag™ Assays to Identify Sub-Populations Within “HER2 Positive” Patient Groups
On Tuesday June 2, 2009, 7:30 am EDT
SOUTH SAN FRANCISCO, Calif.--(BUSINESS WIRE)--Monogram Biosciences, Inc. (Nasdaq:MGRM - News) today announced results from three separate studies at the American Society for Clinical Oncology (ASCO) meeting in Orlando on the use of HERmark® and the VeraTag™ technology to identify distinct sub-populations of patient with HER-positive disease. Monogram’s unique measures of HER family protein levels resulted in improved correlations with the response to trastuzumab and with the histopathologic characteristics of breast cancer, as compared to conventional tests.
“Even when tumors are defined as ‘HER2-positive’, clinical responses to HER2-target therapies are varied, but it hasn’t been clear what accounts for the observed differences in outcome,” said Michael Bates, M.D. Monogram Vice President of Clinical Research. “Taken together, our studies demonstrate the promise of the VeraTag technology to further differentiate those tumors likely to respond to HER2-targeted therapies and aid in the development of personalized treatment strategies for patients with breast cancer.”
The three studies presented at ASCO are:
Quantitative measure of HER3 total protein (H3T) and association with clinical outcomes in HER2 positive metastatic breast cancer patients treated with trastuzumab (abstract #1021):
Study results showed for the first time that adding a quantitative measure of HER3 protein level results in improved stratification of outcomes in patients treated with trastuzumab. Researchers analyzed 81 formalin-fixed tissue embedded tumor samples and sub-divided the patients into HER2 normal and HER2-overexpressing subgroups. The median time to progression (TTP) in the HER2 normal group was 4.1 months whereas the HER2 overexpression patient group has a TTP of 11.1 months (p=0.0002). In this HER2 overexpressing group, high HER3 expression predicted shorter median TTP (6.1 months) compared with low HER3 expression where the median TTP was 13.1 months (p=0.002). The presentation also described enhancements to the performance of the HER3 total protein measure by increasing the sensitivity of the test down to 1,000 receptors per cell and the dynamic range of the assay by 30 fold.
Identification of a sub-population of metastatic breast cancer patients with very high HER2 expression levels and possible resistance to trastuzumab (abstract #1059):
Recent findings demonstrate that a precise and quantitative measure of HER2 protein levels allows for the identification of multiple sub-populations of HER2 positive patients that exhibit different clinical outcomes on trastuzumab. Using the HERmark breast cancer assay, a quantitative measure of HER2 total protein expression was assessed in primary breast tumor specimens from 99 women treated with trastuzumab for their metastatic disease who were also tested for HER2 by FISH. Using sub-population treatment effect pattern plot (STEPP) analysis, a progression free survival (PFS) rate was generated at 12 months after treatment with trastuzumab. Kaplan Meier analyses demonstrated that patients testing HER2 positive with FISH but with very high HER2 protein levels had a PFS that was no better than patients who tested HER2 negative with FISH and had low HER2 protein levels (median PFS of 4.6 months vs. 4.5 months; Hazard ratio = 0.87; p=0.68). In contrast, patients who were FISH positive with intermediate levels of HER2 total protein expression by HERmark had a significantly longer PFS than patients who were FISH negative with low HER2 total protein levels (median PFS 12.6 months vs. 4.5 months; Hazard ratio = 0.34; p<0.0001). Using a novel assay developed by Monogram, it was shown that a proportion of these patients expressed high levels of the p95 C-terminal fragment of HER2, thought to mediate resistance to trastuzumab.
Correlation of quantitative total HER2 expression and HER2 homodimers with histopathologic characteristics of breast cancer in the FinHer Study (abstract # 11061):
Study results add to the evidence that HERmark is an accurate and precise measure of HER2 status. In this study, correlations between HER2 protein expression and histopathologic characteristics of breast cancer- estrogen and progesterone receptor status, tumor grade and stage, tumor size, lymph node metastasis were examined. Using the HERmark breast cancer assay, it was reported that poorly differentiated cancers and those with a negative ER/PR status had higher H2D/H2T ratios (p=0.013) suggesting a more aggressive phenotype. No significant association was found between H2T or H2D and tumor size, tumor stage or lymph node metastatsis.
“These studies represent the continuing development of our suite of VeraTag-based assays that are designed to provide the oncology community with the most comprehensive and accurate information on an individual patient’s tumor profile,” said William Young, Monogram chief executive officer. “Our HER2 protein-based assays consistently provide more accurate diagnostic information than FISH-based tests, and the addition of HER3 protein-based assays will further enhance the information we can offer physicians. We believe that improved understanding of who will or will not respond to HER2 targeted therapies will contribute to a more rational approach to treatment decisions.”
surf's up......crikey
