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ASCO and the CAP Release Updated Guideline on HER2 Testing in Breast Cancer

The American Society of Clinical Oncology (ASCO) and the College of American Pathologists (CAP) recently issued a joint, updated guideline aimed at improving the accuracy and reporting of human epidermal growth factor receptor 2 (HER2) testing in patients with invasive breast cancer. The guideline update is based on a systematic review of medical research literature, providing oncologists and pathologists with detailed recommendations for how to test for HER2 overexpression, interpret the results, and recommend HER2-targeted therapies. The guideline, originally issued in 2007, is being published in ASCO’s Journal of Clinical Oncology (JCO) and the CAP’s Archives of Pathology & Laboratory Medicine. The joint guideline was prepared by an ASCO/CAP Update Committee consisting of experts in breast cancer and cancer biomarkers.

NanoString Technologies Receives FDA 510(k) Clearance for Prosigna Breast Cancer Prognostic Gene Signature Assay

NanoString Technologies, Inc., (NASDAQ: NSTG) a provider of life science tools for translational research and molecular diagnostic products, recently announced that it has received 510(k) clearance from the U.S. Food and Drug Administration (FDA) for its Prosigna™ Breast Cancer Prognostic Gene Signature Assay. Based on the PAM50 gene signature, Prosigna is the company’s first FDA-cleared in vitro diagnostic assay and uses the gene expression profile of cells found in breast cancer tissue to assess a patient’s risk of distant recurrence of disease. The Prosigna Assay is performed using the nCounter® Dx Analysis System, which can be placed in qualified laboratories throughout the United States, empowering oncologists and pathologists to quickly and easily meet the testing needs of their breast cancer patients.

“Receipt of FDA 510(k) clearance for Prosigna marks a key milestone for NanoString and is an important step forward in the treatment of breast cancer. This achievement is a testament to the ongoing dedication and professionalism of our team, and the commitment of our collaborators,” said Brad Gray, President and Chief Executive Officer of NanoString Technologies. “Prosigna illustrates our approach of using nCounter technology to translate genomic discoveries into powerful in vitro diagnostic products, and it represents a significant growth opportunity beyond our robust life sciences research business.”

The Prosigna Assay is intended for use as a prognostic indicator for distant recurrence-free survival at 10 years, and is indicated for postmenopausal women with Stage I/II lymph node-negative or Stage II lymph node-positive (one to three positive nodes) hormone receptor-positive breast cancer who have undergone surgery in conjunction with locoregional treatment consistent with standard of care. For each patient, the Prosigna Assay reports the Prosigna Score (referred to as Risk of Recurrence Score, or ROR Score, in the scientific literature, including the TransATAC study recently published in the Journal of Clinical Oncology ) and a risk category based on both the Prosigna Score and nodal status. Node-negative patients are classified as low, intermediate or high risk, while node-positive patients are classified as low or high risk.

Other key features of the Prosigna Breast Cancer Prognostic Gene Signature Assay include:

  • All-in-one assay consumables, including RNA extraction kits, allowing laboratories to test as little as a single section of formalin-fixed paraffin embedded (FFPE) tumor tissue
  • High-throughput workflow allowing each nCounter Dx Analysis System to process up to 30 patient samples per eight hour work day
  • Automated generation of personalized full-color patient reports that can be quickly and easily shared electronically with ordering oncologists

Bruce Seeley, Senior Vice President & General Manager of Diagnostics of NanoString Technologies commented: “We believe that the compelling clinical data, clear patient reporting, and unique delivery model position Prosigna for success in the U.S. market. By integrating the Prosigna Assay into existing laboratory workflows, we are offering physicians and patients seamless and timely access to clinical insights and a powerful tool that can aid in making more informed treatment decisions.”

Prosigna-enabled nCounter Dx Analysis Systems are expected to be available for placement in high-complexity Clinical Laboratory Improvement Amendments (CLIA) certified laboratories late in the fourth quarter of 2013. Prosigna testing services are expected to be available through qualified U.S. clinical laboratories beginning in the first quarter of 2014.

Source: NanoString Technologies

Promising Screening Tool for Early Detection of Ovarian Cancer

Evaluating its change over time, CA-125, the protein long-recognized for predicting ovarian cancer recurrence, now shows promise as a screening tool for early-stage disease, according to researchers at The University of Texas MD Anderson Cancer Center.

The updated findings are published in Cancer; preliminary data were first presented at the 2010 American Society of Clinical Oncology (ASCO) annual meeting. If a larger study shows survival benefit, the simple blood test could offer a much-needed screening tool to detect ovarian cancer in its early stages – even in the most aggressive forms – in post-menopausal women at average risk for the disease.

MD Anderson has a long history in the research of the important biomarker. In the 1980s, Robert Bast, M.D., vice president for translational research at MD Anderson and co-investigator on the ASCO study, discovered CA-125 and its predictive value of ovarian cancer recurrence. Since then, researchers at MD Anderson and beyond have been trying to determine its role in early disease detection. The marker, however, can become elevated for reasons other than ovarian cancer, leading to false positives in early screening.

“Over the last ten years, there’s been a lot of excitement over new markers and technologies in ovarian cancer,” said Karen Lu, M.D., professor and chair, Department of Gynecologic Oncology and the study’s corresponding author. “I and other scientists in the gynecologic oncology community thought we would ultimately find a better marker than CA-125 for the early detection of the disease. After looking at new markers and testing them head-to-head in strong, scientific studies, we found no marker better than CA-125.”

According to the American Cancer Society, 22,240 women will be diagnosed with ovarian cancer in 2013 and another 14,030 are expected to die from the disease. The challenge, explained Lu, is that more than 70 percent of women with ovarian cancer are diagnosed with advanced disease.

“Finding a screening mechanism would be the Holy Grail in the fight against ovarian cancer, because when caught early it is not just treatable, but curable,” said Lu, also the trial’s principal investigator.

For the prospective, single-arm, 11-year study, 4,051 women were enrolled from seven sites across the country, with MD Anderson serving as the lead site. All were healthy, post-menopausal women, ages 50-74, with no strong family history of breast or ovarian cancer. The study’s primary endpoint was specificity, or few false positives. In addition, the study looked at the positive predictive value, or the number of operations required to detect a case of ovarian cancer.

Each woman received a baseline CA-125 blood-test. Using the Risk of Ovarian Cancer Algorithm (ROCA), a mathematical model based on the patient’s age and CA-125 score, women were stratified to one of three risks groups, with the respective follow-up: “low,” came back in a year for a follow-up blood test; “intermediate,” further monitoring with repeat CA-125 blood test in three months; and “high,” referred to receive transvaginal sonography (TVS) and to see a gynecologic oncologist.

Based on the women’s CA-125 change over time, the average annual rate of referral to the intermediate and high groups were 5.8 percent and .9 percent, respectively. Cumulatively, 117 women (2.9 percent) were determined to be high risk, and thereby received the TVS and were referred to a gynecologic oncologist. Of those women, 10 underwent surgery: four had invasive ovarian cancer; two had borderline disease; one had endometrial cancer and three had benign ovarian tumors – a positive predictive value of 40 percent, which greatly surpasses the clinical benchmark of 10 percent, say the researchers. The specificity of the test was 99.9 percent, explained Lu. The screening failed to detect two borderline ovarian cancers.

Of great importance, said Lu, is that the four invasive ovarian cancers detected were high-grade epithelial tumors, the most aggressive form of the disease, and were caught early (stage IC or IIB), when the disease is not only treatable, but most often curable. Lu also noted that all four women found to have invasive disease were monitored at low risk for three years or more prior to a rising CA-125.

“CA-125 is shed by only 80 percent of ovarian cancers,” explained Bast, the study’s senior author. “At present, we are planning a second trial that will evaluate a panel with four blood tests including CA-125 to detect the cancers we may otherwise miss with CA-125 alone. The current strategy is not perfect, but it appears to be a promising first step.”

While encouraging, the findings are neither definitive, nor immediately practice-changing, stressed Lu; who also said a large, randomized prospective screening trial still needs to be conducted. Such research is ongoing in the United Kingdom; results from more than 200,000 women should be known by 2015.

“As a clinician treating women with this disease for more than ten years, I’ve become an admitted skeptic of ovarian cancer screening. Now, with these findings, I’m cautiously optimistic that in the not too distant future, we may be able to offer a screening method that can detect the disease in its earliest, curable stages and make a difference in the lives of women with this now-devastating disease.”

The study is continuing; and, as follow-up, Lu and her team plan to look at combining other markers with CA-125 to determine the screening impact of their combined change over time.

The study was supported by the National Cancer Institute, and was a research project of MD Anderson’s ovarian cancer Specialized Program of Research Excellence (SPORE), NCI P50 CA83639, the Bioinformatics Shared Resources of MD Anderson CCSG NCI P30 CA16672, the National Foundation for Cancer Research. It has also received philanthropic funds from Golfers Against Cancer, the Tracy Jo Wilson Ovarian Cancer Foundation, the Mossy Foundation, the Norton family and Stuart and Gaye Lynn Zarrow.

In addition to Lu, and Bast, other authors on the study include: Therese Bevers, M.D. Department of Clinical Cancer Prevention, Herbert Fritsche, Ph.D., Department of Laboratory Medicine, Deepak Bedi, M.D., Department of Diagnostic Radiology, Michael T. Deavers, M.D., Department of Pathology and Clinical Pathology; Charlotte Sun, Dr.PH, Department of Gynecologic Oncology, Mary A. Hernandez, Office of Translational Research, all with MD Anderson; Steven Skates, Ph.D., Massachusetts General Hospital and Harvard Medical School; Olasunkanmi Adeyinka, M.D., UT Physicians Family Physicians; William Newland, M.D., The Iowa Clinic; Richard Moore, M.D. and Cornelius Granai, M.D., both with Women & Infants Hospital, Brown University; Leroy Leeds, M.D., OGA Medical Center; Steven Harris, M.D., OB/GYN Associates of Dallas; Jeremy Geffen, M.D., Geffen Cancer Research Institute; and Nora Horick, Harvard Medical School and Massachusetts General Hospital.

As a co-inventor of the CA-125, Bast receives royalties from, and has served as an advisor to, Fujirebio Diagnostics, Inc.

Study: A 2-stage ovarian cancer screening strategy using the Risk of Ovarian Cancer Algorithm (ROCA) identifies early-stage incident cancers and demonstrates high positive predictive value [Cancer]

Source: MD Anderson Cancer Center

Precision Therapeutics Announces Unparalleled Results That Show Recurrent Ovarian Cancer Patients Live 65% Longer in Breakthrough Prospective Clinical Trial

Precision Therapeutics, Inc., a life science company dedicated to developing personalized medicine products for individualized cancer care, recently announced that compelling results have been accepted for publication in Gynecologic Oncology, a leading, peer-reviewed clinical oncology journal. The accepted study is currently located on the Gynecologic Oncology website.

The prospective study, conducted in conjunction with Yale University School of Medicine and over 30 additional cancer centers nationwide, showed that recurrent ovarian cancer patients treated with a chemotherapy identified as sensitive by the ChemoFx® drug response assay lived 14-months longer, a (65%) improvement in overall survival, as compared to patients treated by non-sensitive chemotherapies classified by ChemoFx.

Additionally, ChemoFx was able to identify at least one sensitive chemotherapy agent for more than half of the recurrent ovarian cancer patients studied, approximately doubling current statistics suggesting that only 20 to 30 percent of cancer patients with recurrent ovarian cancer benefit when treated with chemotherapy chosen empirically.

262 evaluable patients were treated with one of 15 study-designated standard chemotherapy treatments selected by the treating oncologist, who was not informed of the ChemoFx results. When blinded to the results of the assay, physicians treated 25% of patients with a sensitive chemotherapy, while more than half (52%) of the study participants showed at least one assay-sensitive chemotherapy from which they could have benefited had the physician been assay-informed. The data implies that if ChemoFx results were utilized by physicians prior to treatment, the number of patients receiving sensitive treatments, and thereby experiencing improved survival outcomes, could have more than doubled. The study clearly shows that patients treated with sensitive chemotherapies identified by ChemoFx outperformed patients treated with alternate chemotherapies.

Median progression free survival also improved by 50% for patients treated with sensitive chemotherapies as identified by ChemoFx vs. those treated with non-sensitive agents (hazard ratio [HR] = 0.67, p = 0.009). The association with assay response was consistent in both platinum-sensitive and platinum-resistant tumors (HR: 0.71 vs. 0.66) and was independent of other covariates in multivariate analysis (HR = 0.66, p = 0.020). A statistically significant 14-month improvement in median overall survival (37.5 months for patients treated with sensitive agents vs. 23.9 months for who were not, HR = 0.61, p = 0.010) was also reported.

“This clinical study is a landmark for the treatment of ovarian cancer because it is the first prospective data that definitively shows that a personalized diagnostic test can make a significant clinical impact by improving overall survival by 65% in women with this devastating cancer,” said Thomas J. Rutherford MD, PhD, Professor of ObGyn and Reproductive Sciences and Section Chief, Gynecologic Oncology at the Yale School of Medicine, and lead investigator in the study.

ChemoFx results show a dramatic difference when compared to recent recurrent ovarian cancer studies that produced limited improvements in progression free survival (2-3 months), and very few if any improvement in overall survival (2 months)2-14

This breakthrough study shows that through the use of the ChemoFx assay, treating physicians can treat with effective chemotherapy drugs which may help extend the life of patients afflicted with this disease. No recent test, therapy or innovation compares in terms of impact on patient’s lives and it is reason for new hope for the treatment of this disease.

“The clinical significance of this study is that ChemoFx may have predictive abilities, enabling a physician to choose the most effective pharmaceutical treatment from among the available options for ovarian cancer,” said Robert Holloway, MD, Medical Director of Florida Hospital Gynecologic Oncology.

Study: A prospective study evaluating the clinical relevance of a chemoresponse assay for treatment of patients with persistent or recurrent ovarian cancer [Gynecologic Oncology]

Source: Business Wire

Study Published in The Journal of Clinical Oncology Demonstrates Advantages of NanoString’s Prosigna Breast Cancer Assay

NanoString Technologies, Inc. (NASDAQ: NSTG), a provider of life science tools for translational research and molecular diagnostic products, recently announced that the TransATAC clinical validation study for its Prosigna Breast Cancer Prognostic Gene Signature Assay, which is based on the PAM50 gene signature, was published in the Journal of Clinical Oncology (JCO). This study, portions of which were initially presented at the 2011 CTRC-AACR San Antonio Breast Cancer Symposium, evaluated the ability of three breast cancer tests to predict risk of distant recurrence after endocrine therapy in postmenopausal women with hormone receptor-positive (HR+) early-stage breast cancer. The authors of the study concluded that the PAM50-based assay provides more prognostic information in endocrine treated patients with HR+ node negative disease than Oncotype DX®, with better differentiation of intermediate and high-risk groups.

The study included 1,017 samples from the landmark ATAC (Arimidex, Tamoxifen, Alone or in Combination) trial of postmenopausal women with HR+ early-stage breast cancer treated with five years of endocrine therapy. The study was performed on RNA extracted from tumor samples by Genomic Health, Inc. for validation of the Oncotype DX® Breast Cancer Assay. The goals of the TransATAC study were to determine if the PAM50 gene signature added prognostic information to clinical-pathological variables and to compare the performance of the PAM50 risk of recurrence (ROR) score, the Oncotype DX recurrence score (RS), and the IHC4 score, derived from immunohistochemical assessment of ER, PR, HER2 and Ki67 genes, in indicating risk of distant recurrence after endocrine therapy. All primary and secondary endpoints of the study were met.

Authors of the study reported that the PAM50 ROR score added prognostic information about the risk of 10-year distant recurrence in addition to that provided by standard clinical-pathological variables in the analysis of all patients studied (p < 0.001). Similar results were achieved in all three prospectively defined clinically important subsets of patients: node-negative (p < 0.001), node-positive (p = 0.002), and HER2-negative (p < 0.001). In addition, the study reported that patients with Luminal A subtype had a lower risk of recurrence than those with the Luminal B subtype further supporting the biological differences between these groups. The authors also concluded that the PAM50 ROR score provided more prognostic information than the widely used Oncotype DX RS. Compared to Oncotype DX RS, PAM50 ROR score categorized fewer patients as intermediate-risk and more as high-risk when using prospectively defined risk cutoffs for low, intermediate and high risk of <10%, 10% to 20% and >20% estimated risk of recurrence, respectively. Moreover, the authors concluded that the PAM50 ROR score provided at least as much information as the IHC4 and may provide more information than IHC4 in the node negative/HER2 negative patient group.

“The publication of the TransATAC study is an important milestone in our ongoing effort to enable genomic testing for breast cancer in local laboratories worldwide,” said Brad Gray, President and Chief Executive Officer of NanoString Technologies. “We look forward to discussing the results and conclusions of this study with oncologists, pathologists, and payers in the European Union and other countries that recognize the CE Mark, as we continue with our commercial launch in those regions.”

Study: Comparison of PAM50 Risk of Recurrence Score With Oncotype DX and IHC4 for Predicting Risk of Distant Recurrence After Endocrine Therapy

Source: Business Wire