Posts Tagged ‘Oncotype DX’

Prostate Cancer Molecular Diagnostic Market – the Players are: SRI Int’l, Genomic Health w/Cleveland Clinic, Myriad Genetics w/UCSF, GenomeDx and BioTheranostics

Curator: Aviva Lev-Ari, PhD, RN


Genomically Guided Treatment after CLIA Approval: to be offered by Weill Cornell Precision Medicine Institute

On May 16, 2013 we reported a major breakthrough in the Prostate Cancer Screening

A Blood Test to Identify Aggressive Prostate Cancer: a Discovery @ SRI International, Menlo Park, CA

After nearly a decade, my collaborators and I have found the first marker that specifically identifies the approximately six to eight percent of prostate cancers that are considered “aggressive,” meaning they will migrate to other parts of the body, at which point they are very difficult to treat. Although we have confirmed this marker, there is much to be done before a clinical application can be developed.


Prostate Cancer MDx Competition Heating Up; New Data from Genomic Health, Myriad

May 15, 2013

Life sciences companies are gearing up for battle to capture the profitable prostate cancer molecular diagnostic market.

Genomic Health and Myriad Genetics both made presentations to the investment community last week about their genomic tests that gauge a man’s risk of prostate cancer aggressiveness. As part of its annual investor day, Myriad discussed new data on its Prolaris test, which analyzes the expression level of 46 cell cycle progression genes and stratifies men’s risk of biochemical recurrence of prostate cancer. If the test reports low gene expression, then the patient is at low risk of disease progression, while high gene expression is associated with disease progression.

Meanwhile, around the same time last week, Genomic Health launched its Oncotype DX prostate cancer test and presented data from the first validation study involving the diagnostic. The Oncotype DX prostate cancer test analyzes the expression of 17 genes within four biological pathways to gauge prostate cancer aggressiveness. The test reports a genomic prostate score from 0 to 100; the lower the score the more certain a patient can be that they can avoid treatment and continue with active surveillance. Prostate cancer patients who are deemed to be at very low risk, low risk, or intermediate risk of progressing are eligible to be tested with the Oncotype Dx test. If, based on standard clinical measures, a person’s prostate cancer is considered high risk, then he is not a candidate for Genomic Health’s test.

These molecular tests are entering the market at a time when currently available tools aren’t specific enough to distinguish between men who have an aggressive form of prostate cancer and therefore, need invasive treatments, and those that are low risk and can do well with active surveillance. According to an NIH estimate, in 2010, the annual medical costs associated with prostate cancer in the US were $12 billion.

It is estimated that each year 23 million men undergo testing for prostate specific antigen, a protein produced by the prostate gland that increases when a man has prostate cancer. Additionally, one million men get a prostate biopsy annually, while 240,000 men end up with a diagnosis for prostate cancer, and around 30,000 die from the disease. Although most of the men diagnosed with prostate cancer end up receiving surgery or radiation treatment, as many as half of these men will probably not progress, and their disease isn’t life threatening.

While PSA testing has been shown to reduce prostate cancer deaths, a man’s PSA level may be increased for reasons other than cancer. As such, broadly screening men for PSA has been controversial in the healthcare community since the test isn’t specific enough to gauge which men are at low risk of developing aggressive prostate cancer and can forgo unnecessary treatments that can have significant side effects.

Both Myriad and Genomic Health are hoping their tests will further refine prostate cancer diagnosis and help doctors gain more confidence in determining which of their patients have aggressive disease and which are at low risk.

Myriad’s advantage

In this highly competitive space, Myriad has the first mover advantage, having launched Prolaris three years ago. The company has published four studies involving the test and conducted a number of trials analyzing around 3,000 patient samples.

Researchers from UCSF and Myriad recently published the fourth validation study in the Journal of Clinical Oncology, which analyzed samples from 400 men who had undergone a radical prostatectomy. In the published study, researchers reported that 100 percent of the men whom Prolaris deemed to be at “low risk” of progression did not experience a recurrence within the five years the study was ongoing. Meanwhile, 50 percent of those the test deemed to be a “high risk” did experience recurrence during that time (PGx Reporter 3/6/2013).

At a major medical conference recently, Myriad presented data from a study which tested biopsy samples from 141 patients treated with electron beam radiation therapy and found that the test score was significantly associated with patients’ outcome and provided information about disease progression beyond standard clinical measures. Although this finding needs to be further validated in a larger patient cohort, the researchers concluded that Prolaris “could be used to select high-risk men undergoing electron beam radiation therapy who may need combination therapy for their clinically localized prostate cancer.” In this study, around half of the cohort was African American.

Myriad has also shown in studies that its test can make accurate predictions from tissue from an initial prostate biopsy and from post-prostatectomy. The test has also shown in studies to be superior to the Gleason score, baseline PSA levels, and other prognostic factors in predicting prostate cancer-specific mortality.

Myriad has nearly completed hiring a 24-person sales force to drive sales of the test. Over the last year, Myriad has received more than 3,000 orders for its Prolaris test and 350 urologists have ordered it. The test carries a $3,400 price tag.

Although the company doesn’t have Medicare coverage yet for Prolaris, Myriad is conducting a study, called PROCEED, that it hopes will sway Medicare contractor Noridian to cover the diagnostic. The company has said it is on track to submit data from this registry to Medicare by late summer and expects to hear a decision about test coverage in calendar year 2014 (PGx Reporter 5/8/2013).

During the annual investor day last week, Myriad officials highlighted the gene panel for Prolaris, which features genes involved in cell cycle progression, and noted this as one of the advantages of its test over standard methods. “The Prolaris score measures how fast the tumor is growing. We look at the cell proliferation to look at a component of cancer that is not looked at by current clinical pathologic features,” Bill Rusconi, head of Myriad’s urology division, said.

“So, pathology like PSA score … only look at how far the tumor is progressed … [and] how advanced that tumor is. So, that’s only half of the picture because an advanced tumor could have been smoldering for 20 years, and may not go much further in the short term,” he noted. On the other hand, Rusconi added that a less advanced tumor could be progressing very quickly.

Another distinguishing point for the Prolaris test, according to Myriad, is that it is indicated for patients who are deemed to be at low and high risk by standard measures. Prostate cancer patients deemed to be at high risk of progression by standard clinical measures wouldn’t qualify for testing by Genomic Health’s test. Rusconi estimated that if Prolaris tested around 200,000 patients with localized prostate cancer to gauge the aggressiveness of their disease, the market opportunity for the test would be $700 million.

Myriad executives declined to comment on competing prostate cancer molecular tests, particularly Genomic Health’s product, noting that there isn’t a lot of published data to make any judgments. “We haven’t really seen any published data from any other competitor product. And so, I think in the absence of that, until data have made it through the peer review process and been in publication, it’s always difficult to understand exactly what type of information is available,” Mark Capone, president of Myriad Genetics Laboratories, told investors.

New competition

Like Myriad’s BRACAnalysis test, which comprises more than 80 percent of its product revenues, Genomic Health’s Oncotype DX breast cancer recurrence tests is bringing in the majority of its product revenues. However, the company believes that its newly launched Oncotype DX prostate cancer test stands to be its largest market opportunity to date.

Last week, researchers from University of California, San Francisco, presented data from the first validation study involving the Oncotype DX prostate cancer test. The study involved nearly 400 prostate cancer patients considered low or intermediate risk by standard methods such as Gleason score and showed that when the Oncotype DX score was used in conjunction with other measures, investigators identified more patients as having very low risk disease who were appropriate for active surveillance than when they diagnosed patients without the test score.

More than one third of patients classified as low risk by standard measures in the study were deemed to be “very low risk” by Oncotype DX and therefore could choose active surveillance. Meanwhile, 10 percent of patients in the study were found by clinical measures to be at very low risk or low risk, but the Oncotype DX test deemed them as having aggressive disease that needed treatment.

Matthew Cooperberg of UCSF, who presented data from this validation study at the American Urological Association’s annual meeting last week, highlighted this feature of the Oncotype DX prostate cancer test to investors during a conference call last week. He noted that the test not only gauges which low-risk patients can confidently remain with active surveillance, but it also finds those patients who didn’t receive an accurate risk assessment based on standard clinical measures. “It’s also equally important that we identify the man who frankly should not be on active surveillance, because they’re out there,” he said.

Genomic Health has aligned its test with guidelines from the National Comprehensive Cancer Network, which has expressed concern about over-diagnosis and over-treatment in prostate cancer patients. In 2010, NCCN guidelines established a new “very low risk” category for men with clinically insignificant prostate cancer and recommended that men who fall into this category and have a life expectancy of more than 20 years should only be followed with active surveillance. In 2011, NCCN made the active surveillance criteria more stringent for men in the “very low risk” category.

In order to develop the prostate cancer test, Genomic Health collaborated with the Cleveland Clinic on six feasibility studies and selected the gene expression panel after analyzing 700 genes on tissue samples from 700 patients. The commercial test analyzes the expression of 17 genes across four biological pathways.

Genomic Health executives suggested to investors that in determining the aggressiveness of prostate cancer a test that gauges critical genes in multiple pathways involved in the disease, as opposed to just one pathway, may be the better bet.

“After we selected those 700 [candidate] genes, we were completely agnostic as to what the best predictors would be. So, we let the genes do their thing and picked out the best performance,” said Eric Klein, chairman of Glickman Urological and Kidney Institute at the Cleveland Clinic and principal investigator for the original development studies for the Oncotype DX prostate cancer test. Referring to Myriad’s test, which assessed 46 cell cycle progression genes, Klein noted that while cell proliferation is important, it’s not the only pathway.

“So, I think one of the strengths of this assay is that it surveys the biology of the cancer better because it surveys other pathways,” he said. If a test only looks at genes in only one particular pathway, and the “score is low, you don’t know if you have missed the other underlying biology.”

This strategy of picking critical cancer-linked genes from multiple pathways has proven successful when launching Oncotype DX tests for breast cancer and colon cancer recurrence, company officials noted. Genomic Health’s prior experience launching molecular tests for cancer recurrence and the strength of the Oncotype DX brand will likely be advantages for the company.

Kim Popovits, CEO of Genomic Health, noted that the company has hired a “small sales force” to drive uptake of the prostate cancer test and reps will be targeting high-volume practices. “We have medical science liaisons that will be out there working to educate key opinion leaders with a similar approach to what we did in breast [cancer],” Popovits told investors. “We will begin to add to the sales organization as time goes on, as we see traction taking place, and as we move more towards payor reimbursement.”

The company plans to conduct a decision impact study as part of its effort to gain reimbursement coverage for the test. Genomic Health is also planning to do additional studies that will explore what level of active surveillance doctors should perform on patients who are deemed by the Oncotype DX test to be at very low or low risk.

The list price for the test is $3,820.

Other players

Although Myriad and Genomic Health are currently the main players in the prostate cancer molecular diagnostics space, the market will become an increasingly crowded one in the coming months.

Canadian firm GenomeDx is planning to launch a prostate cancer molecular diagnostic later this year, called Decipher. The company recently presented data at a medical conference on the test’s clinical validity and utility in predicting which patients are at risk of recurrence and metastasis after prostate cancer surgery. The company has said it has 22 studies underway with the Decipher test involving 4,000 patients (PGx Reporter 2/20/2013).

BioTheranostics recently published a study in the Proceedings of the National Academy of Sciences about its new 32-gene signature test, dubbed Prostate Cancer Index, which gauges PSA recurrence. In the study, which involved 270 tumor samples for patients treated with radical prostatectomy, the RT-PCR test (developed in collaboration with Massachusetts General Hospital) predicted PSA recurrence and had added value over standard measures such as Gleason score, tumor stage, surgical margin status, and pre-surgery PSA levels. The only other measure with significant prognostic value was surgical margin status.

The test could separate patients into groups based on PSA recurrence and whether they would develop metastatic disease within a 10-year period. PCI found that patients with a high risk score had a 14 percent risk of metastasis, while those in the low-risk group had a zero percent risk of metastasis. “In particular, this information may be useful at the biopsy stage, so that clinicians can better assess which patients can consider active surveillance versus those who should consider immediate treatment,” BioTheranostics CEO Richard Ding told PGx Reporter.

BioTheranostics has not yet determined when it will launch PCI. However, the company is planning additional follow-on studies to demonstrate the clinical utility of the test, including one study involving patients on active surveillance after having an initial prostate biopsy.

      Turna Ray is the editor of GenomeWeb’s Pharmacogenomics Reporter. She covers pharmacogenomics, personalized medicine, and companion diagnostics. E-mail Turna Ray or follow her GenomeWeb Twitter account at @PGxReporter.

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Recurrence Risk for Breast Cancer

Reporter: Larry H Bernstein, MD,  FCAP


Testing recurrence risk for breast cancer
Karen Titus
June 2011 CAP Today



Gene panels for breast cancer recurrence risk have arrived. In fact, they’ve been around since the mid-2000s. And now, like guests at a wedding reception, it’s a matter of figuring out where to seat them.
Like it or not, tests such as Oncotype DX (Genomic Health Inc.), MammaPrint (Agendia), and Mammostrat (Clarient)—to name just a few—are making their presence felt.
Clinicians favor these tests for a simple reason: the results help them decide if patients with breast cancer need chemotherapy. More broadly, the tests reflect a shift in thinking among physicians, one that emphasizes molecular profiling of tumors. They’ve arrived on the scene when physicians are also starting to question the value of lymph node status to help determine treatment.George W. Sledge, MD, finds these changes remarkable. Not all that long ago, he might have pink-slipped a test that would help parse treatment decisions. When the NIH held its consensus development conference on adjuvant therapy with breast cancer in 2000, he recalls, the agreement was, basically, that everyone with a tumor greater than one centimeter ought to be treated with chemotherapy. “There’s no question that resulted in us hugely overtreating patients,” he says. “So I think a test that reduces the quantity of human suffering by half in that group is a useful test,” says Dr. Sledge, professor of medicine and pathology, Indiana University, Indianapolis, and immediate past president of the American Society of Clinical Oncology.
In clinical practice, these tests are functioning like traffic managers. “We now see fewer patients getting chemotherapy who would have gotten it before,” says Thomas Julian, MD, professor of surgery, Drexel University College of Medicine, Philadelphia, and director of breast surgical oncology for the West Penn Allegheny Health Care System, Pittsburgh. “We’re also seeing a few who are getting chemo who might not have gotten it before. So it’s changed in both directions,” says Dr. Julian, who is also senior surgical director for medical affairs for the National Surgical Adjuvant Breast and Bowel Project.
Oncotype DX is a real-time RT-PCR assay measuring RNA expression in 16 cancer-related genes and five reference genes, using paraffin-embedded tissue. Results are given as a recurrence score between zero and 100, which are translated as low risk (a score of 18 or lower), medium risk (19 to 30), or high risk (31 or above). The MammaPrint microarray assay measures expression of 70 genes in fresh tissue; it categorizes patients as either high risk, with a so-called poor signature, or low risk (a so-called good signature) for recurrence. There is no intermediate category. Mammostrat is an immunohistochemistry test measuring five markers: p53, HTF9C, CEACAM5, NDRG1, and SLC7A5. The results are combined into a quantitative risk index: low, moderate, and high. For now, only MammaPrint has FDA clearance.
The test is not useful in patients whose tumors are HER2 positive. The test nearly always will show such patients to be at high risk; moreover, the paradigm for treating such patients is with chemotherapy and trastuzumab (Herceptin). It is used for patients who are lymph node negative, ER positive, and HER2 negative, with “moderate-size tumors—say, tumors that are over a centimeter but less than four or five centimeters. Another consideration is tumor size. The test is most useful for tumors of around five millimeters or greater in size.For patients with very, very small tumors—one, two, three millimeters—there’s no need for the test. Elizabeth Hammond, MD, agrees these tests are useful, although she suspects they may best prove their mettle in second- or third-generation assays. It’s simple biology: phenotypic expression of a genetic alteration of ER or HER2 status is the result of cell-signaling pathway changes. “Looking at multiple expressions of that problem with a gene panel, either by RT-PCR or some other method, will in the long run give us better information.

Comment:  In 1982, labs were running RIA assays for Estrogen Receptor.  It was known for some time that breast cancer is estrogen-dependent.  This was a major discovery by a surgeon at University of Chicago, that led to oophorectomy with resection of the lesion.  The assay was quite elaborate and required a “scatchard plot”.  The assay was no longer used when a good histochemical stain became widely used with a progesterone receptor a few years later.  We went into the 1990’s knowing that if the patient is pre-menopausal, positive ER+/PR+ is likely, and the cancer is aggressive.  If the patient was postmenopausal, the test is more likely ER/PR negative.  This gives us a perspective on how far we have come.

Image representing Genomic Health as depicted ...

Image via CrunchBase

English: Validation chart for Agendia's MammaP...

English: Validation chart for Agendia’s MammaPrint Assay, part of the Symphony Breast Cancer Suite (Photo credit: Wikipedia)

Ovarian and breast cancer patients in a pedigr...

Ovarian and breast cancer patients in a pedigree chart of a family (Photo credit: Wikipedia)

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