Personalized Medicine
Two Genetic Tests Can Prevent Overtreatment of Early Prostate Cancer Oncotype DX prostate cancer test and Prolaris will compete for market share By Phoebe Starr Chicago, IL—The management of patients with prostate cancer will be advanced by 2 new genetic tests—Oncotype DX prostate cancer test and Prolaris. Both tests generate a score that can be used to analyze biopsy specimens of men with low-risk prostate cancer (ie, Gleason score ≤6) to determine if they are truly “low risk” and appropriate for watchful waiting, or if they harbor higher-risk genes and need immediate treatment. These tests, although expensive, have the potential to prevent overtreatment and the associated costs, and to improve decision-making and risk assessment. Studies presented at the 2013 Ameri can Society of Clinical Oncology meeting focused on the 2 tests, which experts believe will compete with each other for market share. Oncotype DX for Prostate Cancer Expecting FDA Approval Launched by Genomic Health on May 18, 2013, the Oncotype DX prostate cancer test is similar to the Oncotype DX breast cancer and colon cancer tests widely used in the United States. The Oncotype DX prostate cancer test measures the expression of 17 genes in a prostate tissue specimen that
can predict the aggressive level of prostate cancer by generating a genomic prostate score ranging from 0 to 100. H. Jeffrey Lawrence, MD, Senior Director of Medical Affairs, Genomic Health, Redwood City, CA, presented data showing that the expression patterns that predict prostate cancer aggressiveness are similar in tumor tissue and in normal prostate tissue.
These genetic tests, although expensive, have the potential to prevent overtreatment of prostate cancer and reduce the associated costs. The genomic prostate score derived from tumor-based gene-expression patterns in the tumor was also associated with clinical recurrence when assessed in adjacent normal prostate tissue, but the strength of the association was less robust than in the tumor. The genes associated with the strong est predictive value of the genomic prostate score in normal tissue were those representing stromal response and androgen signaling.
A validation study of the Oncotype DX prostate cancer test was presented at the 2013 meeting of the American Urological Association by Peter Carroll, MD, Professor and Chair, Department of Urology, University of California, San Francisco. The test significantly predicted disease aggressiveness (P = .002) beyond clinical factors that included prostate-specific antigen level and Gleason score. The test is estimated to cost approximately $3800. Genomic Health is in the process of building a dossier of evidence for insurers. Based on Genomic Health’s strong track record with the breast and colon cancer Oncotype DX assays, the company expects the US Food and Drug Administration (FDA) to grant approval to the prostate test. Prolaris Approved by FDA Prolaris, manufactured by Myriad Genetics, is approved by the FDA for use in low-risk men with a Gleason score of 6, and for patients postprostatectomy who are at high risk for prostate cancer recurrence. Prolaris, which has been available for several months, costs approximately $3400. The assay generates a cell cycle progression (CCP) score based on the av-
erage RNA expression of 31 CCP genes that are normalized by the average expression of 15 housekeeping genes as quantitated by reverse transcriptase polymerase chain reaction. Jack M. Cuzick, PhD, Director, Wolfson Institute of Preventive Medicine, University of London, United Kingdom, presented a retrospective review of 5 studies of the Prolaris test showing that the test-generated CCP score was able to predict prostate cancer outcomes in multiple patient cohorts and in diverse clinical settings. In a statement issued before the meeting, Dr Cuzick said, “Clinical data show that PROLARIS predicts prostate cancer outcome in multiple patient cohorts and in diverse clinical settings. PROLARIS provides independent information beyond clinicopathologic variables and accurately differentiates aggressive prostate cancer from indolent cancer based on real oncologic outcomes.” A similar distribution of CCP scores was found in all 5 studies, showing its utility in different settings. The CCP score was a significant predictor of disease outcome. However, the 5 studies were not randomized; therefore, the results should be interpreted with caution, Dr Cuzick said. n
Strategies to Overcome the Challenges of Personalized Medicine Chicago, IL—The use of molecular profiling to guide treatment decisions is envisioned as a critical new strategy in cancer therapy, but for patients to reap the benefits of personalized medicine, sweeping reforms are needed in how genetic information is analyzed and acted upon, said Richard L. Schilsky, MD, Chief Medical Officer, American Society of Clinical Oncology (ASCO), and Chief of Hematology/ Oncology, Department of Medicine, University of Chicago Comprehensive Cancer Center, IL. Dr Schilsky’s talk at ASCO 2013 was titled, “Breaking Down Barriers in the Implementation of Personalized Medicine.” “We have learned that each person’s tumor has a unique molecular profile. This has generated excitement, but dif-
Photo by © ASCO/Todd Buchanan 2013
By Caroline Helwick
“We have learned that each person’s tumor has a unique molecular profile. This has generated excitement, but difficulty as well, with respect to how we understand the unique biology of each tumor and how we act on this to individualize treatment.”
ficulty as well, with respect to how we understand the unique biology of each tumor and how we act on this to individualize treatment,” he noted. Challenges in Personalizing Treatment Implementing a personalized cancer
—Richard L. Schilsky, MD medicine program requires (1) adequate tumor tissue available for molecular profiling; (2) a standardized, high-quality laboratory for molecular profiling to ensure the accuracy, reliability, and timeliness of test results; (3) identification of tumor “targetable” molecular aberrations; and (4) the availabil-
ity of a targeted agent known to inhibit the activity of the molecular aberration. There are problems inherent in all of these steps. Established guidelines for tissue collection and testing are lacking, while testing facilities are proliferating. “Clinicians are having a hard time figuring out which lab to use, which gives the most reliable results. And there are few established standards for the molecular workup of tumors,” Dr Schilsky said. Dr Schilsky proposed that ASCO and the College of American Pathologists collaborate on developing guidelines for tissue handling and molecular workup. Guidelines established by professional societies will ensure that laboratories across the country meet uniform proficiency standards and produce high-quality results. Continued on page 28
VOL. 6
I
NO. 6
I
Special Issue
august 2013
I
www.AHDBonline.com
27