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Archives for January 2013

Researchers Discover Promising Prognostic Marker for Aggressive Breast Cancer

A team of researchers led by Goutham Narla, MD, PhD, at Case Western Reserve University School of Medicine and University Hospitals Case Medical Center, and collaborators at the Mount Sinai School of Medicine and Erasmus Medical Center, have discovered a gene variant that drives the spread of breast cancer. Published in Science Translational Medicine, the study lays the early foundation for predicting which breast cancer patients may develop more aggressive disease and for designing more effective treatments.

“Breast cancer is a genetically complex disease and it remains a challenge to predict disease outcomes and which patients may benefit from more aggressive treatment,” says Dr. Narla, assistant professor at Case Western Reserve University School of Medicine and medical geneticist at UH Case Medical Center Seidman Cancer Center. “Our research has uncovered a promising gene marker that will not only help us better identify tumors that behave badly but provide a basis for developing and ‘personalizing’ therapies to better treat our patients.”

The research team discovered that a mutant gene, KLF6-SV1, was linked to the recurrence and metastasis in women with breast cancer. The incorrect splicing of the KLF6 gene essentially creates a protein that causes cancer cells to spread or metastasize. The researchers examined the tumors of 671 breast cancer patients in a tumor bank at Erasmus University Medical Center (Rotterdam, The Netherlands) and found that those whose tumors expressed high levels of the gene variant were 50 percent more likely to die. Since recurrence and metastasis are the major causes of death in breast cancer, this finding will provide a new direction of research to both identify women at risk and to develop targeted drugs that block the process of metastasis.

“This study presents biological proof that this splice variant can potentially be a marker for determining which early stage breast cancer patients will have disease progression,” adds Dr. Narla. “More studies need to be done, but this could provide an important prognostic marker to determine which patients need to be treated more aggressively or watched more closely.”

Dr. Narla came to UH Case Medical Center and Case Western Reserve in spring, 2012, from Mt. Sinai and is the first Harrington Distinguished Scholar (Early Career Award). This inaugural award provides physician-scientists with the ability to tap into grant funding and a peer network of innovators and mentors within the infrastructure of the Harrington Discovery Institute at UH Case Medical Center. The Institute is part of the $250 million Harrington Project for Discovery & Development, which was launched in February, 2012, with a $50 million gift to UH from the Harrington family of Hudson, OH.

Dr. Narla’s laboratory focuses on the identification and characterization of the genes and pathways involved in cancer metastasis. By studying the functional role of the KLF6 tumor suppressor gene, Dr. Narla and his team have identified new signaling pathways regulated by this gene family thus providing new insight into cancer diagnosis and treatment. The team’s research found that KLF6 and FOXO1, both tumor suppressor genes, are turned off as cancer spreads through the body. Since first discovering the KLF6 gene 13 years ago as a medical student at Mount Sinai School of Medicine in the laboratory of Dr. Scott Friedman, Dr. Narla has been involved in the identification and characterization of the gene and its role in cancer development.

“In this new research as well as previous studies, Goutham and his team have uncovered important and previously unrecognized genetic markers in cancer,” said Stanton Gerson, MD, Director of the Case Comprehensive Cancer Center and the UH Case Medical Center Seidman Cancer Center. “This work highlights how understanding the basic mechanisms regulating cancer development and progression can lead to significant advances in the treatment of cancer. We are so pleased to have a physician-scientist of his caliber at our cancer center and are excited about the impact of this important work.”

Dr. Narla will work with the breast cancer team, led by Lyndsay Harris, MD, to study further KLF6-SV1’s potential as a prognostic marker for patients with poor outcomes. The group also will work to develop novel therapeutics that can turn the protein off and cause the cells to become less aggressive.

“We look forward to continuing this work to further define the role of KLF6-SV1 on the molecular basis of tumor progression and metastasis in breast cancer,” says Dr. Harris, Director of the Breast Cancer Program at UH Case Medical Center and Professor, Medicine-Hematology/Oncology at the School of Medicine. “These findings provide us with a biomarker of more aggressive disease and a target for new therapies. This will potentially enable us to develop more “personalized” treatments for patients and thereby reduce breast cancer mortality.”

This work was supported by the Howard Hughes Medical Institute (HHMI). Additional support for Dr. Narla’s research comes from the Case Comprehensive Cancer Center, Case Western Reserve University School of Medicine, Case Western Reserve University Institute for Transformative Molecular Medicine, and the Mount Sinai School of Medicine. Dr. Narla is also supported by an early physician scientist career award from the HHMI.

Study: KLF6-SV1 Drives Breast Cancer Metastasis and Is Associated with Poor Survival

Source: University Hospitals Case Medical Center

Genomic Health Announces New Evidence Further Demonstrating Clinical Utility and Cost-Effectiveness of Oncotype DX in Colon Cancer

Genomic Health, Inc. (Nasdaq: GHDX) today announced results from three studies of the Oncotype DX® Colon Cancer test at the 2013 Gastrointestinal (GI) Cancers Symposium, including new data demonstrating that Recurrence Score® (RS) results changed treatment recommendations in 45 percent of the enrolled stage II colon cancer patients. Presentations also include positive findings from a second health economics analysis suggesting that use of the test may result in a significant reduction in direct medical costs and improve patient well-being.

Additionally, the company announced that the Journal of Clinical Oncology (JCO) has accepted for publication results from its second large clinical validation study of stage II colon cancer patients enrolled in CALGB 9581 confirming that the Oncotype DX test improves the ability to differentiate higher from lower recurrence risk beyond conventional factors.

“These new data reinforce the value of an individualized recurrence risk assessment score that enables physicians to identify those at high risk of recurrence who can experience a greater potential benefit from chemotherapy, as well as patients with a low risk of recurrence who can be spared unnecessary treatment,” said Steven Shak, M.D., chief medical officer and executive vice president for research and development at Genomic Health. “Oncotype DX represents an important advance in bringing personalized medicine into the modern paradigm for cancer care. With a growing body of evidence, and a second publication in JCO, we now have expanded support for broader reimbursement and increased patient access to our colon cancer test.”

Oncotype DX Colon Cancer Test Changes 45 Percent of Treatment Decisions

“Current clinical practice reveals a high level of variability and subjectivity in the treatment of stage II colon cancer patients,” said Steven Alberts, M.D., medical director for the Clinical Research Office in the Mayo Clinic Cancer Center, Rochester, Minn. “The Oncotype DX Colon Cancer test changes the paradigm for predicting individual recurrence risk for stage II colon cancer patients by providing quantitative information which has not been available with conventional measures.”

  • Conducted in collaboration with the Mayo Clinic Cancer Research Consortium, a prospectively designed study analyzed treatment decisions for 141 stage II, T3 MMR-proficient colon cancer patients across 17 sites demonstrating that the use of the Oncotype DX Colon Cancer test changed treatment decisions 45 percent of the time and led to an overall reduction in chemotherapy use.

For patients whose treatment recommendations changed, treatment intensity decreased for more than 33 percent of patients (from chemotherapy to observation or from oxaliplatin-containing to non-oxaliplatin containing regimens) and increased for more than 11 percent of patients (from observation to any chemotherapy or from non-oxaliplatin containing to oxaliplatin-containing treatment).

Abstract #453: “Prospective evaluation of a 12-gene assay on treatment recommendations in stage II colon cancer patients” will be presented on Saturday, January 26, from 7:00—7:55 a.m. Pacific Time at Moscone West, San Francisco, Calif.

Second Health Economics Study Reconfirms Test’s Cost Effectiveness

  • An analysis of 141 patients from 17 sites in the Mayo Clinic Cancer Research Consortium demonstrated the value of using the Oncotype DX test to identify stage II colon cancer patients with low risk of recurrence. After receiving the Recurrence Score results, physician recommendations for adjuvant chemotherapy in patients with low risk of recurrence decreased by 22 percent, which resulted in direct medical care costs savings of $4,200 per patient.

This is the first health economic study of the Oncotype DX Colon Cancer test conducted in clinical practice. A separate modeling study showing that the use of the Oncotype DX test in stage II colon cancer patients may lead to health care cost savings while improving clinical outcomes was recently published in the December 2012 issue of Value of Health.

Abstract #391: “Real-world comparative economics of a 12-gene assay for prognosis in stage II colon cancer” will be presented on Saturday, January 26, from 7:00—7:55 a.m. Pacific Time at Moscone West, San Francisco, Calif.

Additionally, a poster titled: “Impact of the Recurrence Score (RS) result and mismatch repair status (MMR) on agreement between oncologists (MDs) for stage II colon cancer (CC) recurrence risk (RR) assessment: A novel clinical utility endpoint for prognostic markers” (Abstract #349) will be presented on Saturday, January 26, from 7:00 – 7:55 a.m. Pacific Time at Moscone West, San Francisco, Calif.

Four leading medical specialty societies co-sponsor the three-day, multidisciplinary symposium, including the American Gastroenterological Association Institute, the American Society of Clinical Oncology, the American Society for Radiation Oncology and the Society of Surgical Oncology (SSO).

Source: Genomic Health

Tumors Evolve Rapidly in a Childhood Cancer, Leaving Fewer Obvious Treatment Targets

An extensive genomic study of the childhood cancer neuroblastoma reinforces the challenges in treating the most aggressive forms of this disease. Contrary to expectations, the scientists found relatively few recurrent gene mutations—mutations that would suggest new targets for neuroblastoma treatment. Instead, say the researchers, they have now refocused on how neuroblastoma tumors evolve in response to medicine and other factors.

Selventa Developing Powerful New Class of Multi-omic Based Diagnostic Test for Autoimmune Disease and Cancer

Last week Selventa announced that it is developing a powerful new class of diagnostic test that will accelerate the implementation of personalized healthcare. Systems Diagnostics, or SysDx™, will be a novel diagnostic tests that can consist of “multi-omic” biomarkers selected through a rigorous Big Data analysis of a patient’s biological profile including genomic, epigenomic, transcriptomic, proteomic, metabolomic and electronic medial record information. From this analysis, Selventa will generate a differentiated and clinically-relevant report that physicians and patients can use to improve therapy selection.

FDA Accepts Supplemental New Drug Application for Tarceva (Erlotinib) Tablets for Genetically Distinct Form of Advanced Lung Cancer

Astellas Pharma US, Inc. (“Astellas”), a U.S. subsidiary of Tokyo-based Astellas Pharma Inc. (Tokyo: 4503), recently announced that the U.S. Food and Drug Administration (FDA) has accepted for filing a supplemental New Drug Application (sNDA) for Tarceva® (erlotinib) for first-line use in people with locally advanced or metastatic non-small cell lung cancer (NSCLC) whose tumors have epidermal growth factor receptor (EGFR) activating mutations. The application has been granted Priority Review status, and an FDA decision is expected in the second quarter of 2013. A pre-market approval (PMA)
application for a companion diagnostic, the cobas® EGFR Mutation Test developed by Roche Molecular Diagnostics, has also been submitted to the FDA.