Response Genetics Inc. (Nasdaq:RGDX), a company focused on the development and sale of molecular diagnostic tests for cancer, announced the results of two separate analyses at national medical conferences.
“Based upon strong scientific and medical evidence, the use of predictive biomarkers in the clinical setting is gaining acceptance”
- The first study investigated the association of EGF receptor (EGFR) activating mutations and expression of the DNA repair gene ERCCI in non-small cell lung cancer (NSCLC). Results indicate that tumors with mutations that increase the activity of EGFR inhibitors are also more likely to express low levels of the ERCC1 gene. Low levels of ERCCI are a molecular marker associated with platinum-based chemotherapy sensitivity.
These findings were presented orally by Dr. David R. Gandara, University of California, Davis Cancer Center, at the Late Breaking Abstract session of the 2010 Chicago Multidisciplinary Symposium in Thoracic Oncology, which was held December 9-11 in Chicago, IL.
- In the second study, investigators assessed the utility of limited gene profiling as a predictor of response to neoadjuvant chemotherapy in locally advanced and inflammatory breast cancer. Patients were treated with docetaxel, doxorubicin, cyclophosamide (TAC) or AC and Nab-paclitaxel and carboplatin +/- trastuzumab. Expression levels of HER2, EGFR, p27, IGFR1 and BRCA2 were associated significantly with complete pathological response (pCR) to the neoadjuvant chemotherapies in these patients. Findings from this analysis suggest that specific gene products may indeed play a role in therapeutic response to chemotherapy agents.
The results were presented by Dr. George Somlo, City of Hope Cancer Center, at the 33rd Annual San Antonio Breast Cancer Symposium, which was held December 8-12 in San Antonio, TX.
By attempting to understand the underlying regulatory mechanisms that control tumor growth and activity of anti-cancer therapies, both studies support the importance of identifying those factors that drive therapeutic benefit in individuals. With such knowledge, physicians will be better able to personalize their patients' care.
"Platinum-based drugs are the most commonly used chemotherapy agents today, yet they fail in the majority of patients," said David R. Gandara, M.D., professor of medicine, associate director of clinical research and director of the Thoracic Oncology Program, University of California Davis Cancer Center. "Here we have shown that cancers that are more sensitive to EGFR blockade may also be more sensitive to platinum chemotherapy. Understanding which genes correlate with a drug's beneficial effects will help doctors identify those patients most likely to benefit. Moving these findings into clinical practice is the next step."
"Based upon strong scientific and medical evidence, the use of predictive biomarkers in the clinical setting is gaining acceptance," said Kathleen Danenberg, president and CEO of Response Genetics. "Results such as ours are paving the way to getting the right drug to each patient the first time."
All studies presented used technology developed by Response Genetics to isolate RNA from formalin-fixed, paraffin-embedded (FFPE) archived tissue for quantitative RT-PCR analysis of gene expression. Following is a summary of presentations:
Abstract P2-09-17: Presented Friday, December 10, 7:00 to 9:00 a.m.
Limited gene expression profiling as predictor of response to neoadjuvant chemotherapy with docetaxel, doxorubicin, cyclophosphamide (TAC), or AC and Nab-paclitaxel and carboplatin +/- trastuzumab in patients with locally advanced Stage II-III and inflammatory breast cancer.
Pathologic complete response (pCR) following neoadjuvant chemotherapy may be a predictor of improved survival. To more effectively individualize regimens in patients with inflammatory breast cancer, researchers sought to identify molecular markers that correlate therapeutic response and/or resistance with pCR. Results show that overexpression of HER2, EGFR and BRCA2, and low expression of p27 and IGFR1 were observed in patients that achieved pCR. And when the analysis was restricted to HER2 negative cases, BRCA2 and JAK2 overexpression and low expression of IGFR1 were associated with pCR. Based on the feasibility of obtaining tissue samples before neoadjuvant chemotherapy, testing for specific genes may help determine therapeutic response in HER2+ and HER2-, locally advanced and inflammatory breast cancer.
Abstract 119: Presented Friday, December 10, 2:15 to 3:15 p.m.
Association of EGFR-activating mutations with low ERCC1 gene expression in non-small cell lung cancer: Assessment of 1,207 patients.
Published studies show that patients with NSCLC whose tumors harbor activating EGFR mutations show improved response to tyrosine kinase inhibitor-based therapy. Other studies suggest enhanced efficacy of platinum-based chemotherapy or radiotherapy in patients with EGFR mutant cancers. In this study, investigators examined the relationship between EGFR mutation status and DNA repair capacity, as exemplified by ERCC1 gene expression, as a potential explanation for this observation. Results show that NSCLC patients with EGFR activating mutations are more likely to express low ERCC1 mRNA levels. Based on these findings, a prospective trial (CASTLE) is underway to determine whether these results translate into enhanced clinical efficacy of EGFR-mutant cancers to platinum-based chemotherapy.
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