Taking a Leap in Cancer Diagnostics: Clarient Enters New Era in Molecular Tumor Testing, Drug Discovery Research

Kenneth J. Bloom, MD Chief Medical Officer Clarient, Inc

When Kenneth J. Bloom, MD, began his career in pathology more than 25 years ago, the field of genomic and molecular diagnostics in cancer therapeutics was virtually nonexistent. Today, the sector is exploding and Bloom is at the forefront of efforts to develop new oncologic tools and bring them to clinical practice.

Bloom is the chief medical officer of Clarient, Inc, a once-fledgling company that GE Healthcare acquired in December 2010 for $425 million.

Clarient provides more than 350 diagnostic tests to assess and characterize tumors, including tests for BRAF, KRAS, and EGFR gene mutations, as well as the recently launched Clarient InsightDx Mammostrat test for breast cancer recurrence. The company also offers PATHSITE, an Internet-based service where physicians can view and manage digital images, patient case histories, and test results.

In December, Clarient announced a partnership with ACORN Research, LLC, a network of community oncology practices and hospitals, through which tumor-specific biomarker data for each new patient will be collected and analyzed under standardized protocols. The data will be used to personalize treatment for individual patients, as well as to build a databank of information about particular tumor types that can be used in clinical trials and other research.

Such developments are likely to mean a big jump forward not only for the Aliso Viejo, California-based company, but also for patients, according to Bloom.

“This is the perfect storm,” Bloom said in an interview. “All of the things that are necessary are coming together as one. We can really start bringing the highest level of care to every patient anywhere within the United States, and then eventually anywhere in the world. It is incredibly exciting.”

“It’s something that five years ago nobody could have contemplated,” he added. “If you were sick in rural Georgia, you would have to go to Atlanta. But those days are changing. You’re going to be able to get access to the same level of care no matter where you are.”

Bloom said GE ownership will boost Clarient’s ability to expand internationally, while the ACORN partnership will enable the company to compare outcomes with clinical trial results and conduct drug discovery research.

“To me, when we talk about personalized healthcare, it means giving healthcare locally,” he added. “It means you don’t pick up and travel 200 miles to some other institution where your family and friends can’t visit you and you undergo therapy in isolation. If that care could be given locally with your family and friends around you, that would be hugely advantageous. I think that’s what we’ve really been striving for all along, and it’s achievable.”

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To me, when we talk about personalized healthcare, it means giving healthcare locally. It means you don’t pick up and travel 200 miles to some other institution where your family and friends can’t visit you and you undergo therapy in isolation. ”

—Kenneth J. Bloom, MD

Growing With Community Oncologists in Mind

The trends now shaping the cancer diagnostics field in some ways mirror the trajectories of both Bloom’s career and Clarient’s corporate evolution.

Now, as a result of the sequencing of the human genome and advances such as polymerase chain reaction and microarray technology, the options in genomic and molecular testing in cancer diagnostics are expanding dramatically.

“When I went through medical school, molecular pathology didn’t exist,” Bloom said. “So I got zero molecular pathology in medical school, zero molecular pathology in residency. It’s really only the last 10 or 15 years of my practice that molecular pathology has come to the forefront.”

Bloom, who became a member of the College of American Pathologists in 1987, held a number of positions related to oncology at Rush-Presbyterian- St. Luke’s Medical Center, now Rush University Medical Center, in Chicago, Illinois, for more than 20 years before joining US Labs as senior medical director in 2002.

Within a few years, the Irvine, California, cancer diagnostics company was purchased by industry giant LabCorp. Bloom, who moved on to Clarient in August 2004, said he shared Clarient’s philosophy of partnering with local pathologists rather than supplanting them with a centralized lab.

Clarient itself has grown from a small company launched in the early 1990s to develop medical imaging technologies into a 400-employee business focused on diagnostics.

General Electric Company, which operates GE Healthcare, said in its 2010 annual report that Clarient was a “leading player” in a rapidly growing market, and that its purchase of the company would accelerate GE’s presence in the field. The demand for cancer diagnostics is expected to grow from $15 billion in 2010 to $47 billion by 2015, GE said.

Although the acquisition is an example of the consolidation in the industry, Bloom believes Clarient maintains a business model that preserves both local pathologists, and helps the community oncologists and hematologists with whom they work.

“We really had a passion of bringing cancer testing directly to local pathologists and hence local oncologists,” Bloom said. “The idea was that we would never compete with the local pathologists. The things that a local pathologist knew how to do, and do well, they should do.

“But all of the advanced things that they should be doing but didn’t have access to, either because they didn’t have the space, the resources, the training, or the technicians, we would not only provide that test to them, but we also would engage them in the process, and we would educate them along the way,” he said. “And that’s been an incredibly successful model.”

The GE Healthcare acquisition gives Clarient the resources to expand its model worldwide and to pursue original research, Bloom said. “Now we can lead the charge and develop the next generation of tests that will lead the way to personalized healthcare,” he said.

The Clarient InsightDx Mammostrat

Emphasizing Role of Pathologists Amid Change

As the options in cancer diagnostics grow in number and complexity, Bloom believes oncologists will be bombarded with choices they might not be equipped to evaluate. That is why he feels pathologists are vital members of the treatment team.

“Probably the biggest question for oncologists is, ‘How do I deal with all these new tests that are coming on the market?’” he said.

“To me, it’s not obvious that just because there’s a new test, that everybody should instantly understand how that test works and how to apply it,” Bloom said. “There’s going to have to be experts that understand how to do that.”

In Bloom’s view, local pathologists should supply that expertise by working with oncologists and with labs such as Clarient that offer advanced testing.

“The pathologist can be your biggest tool, because they are charged with understanding all of the tests, monitoring the performance of those tests, and discovering why laboratory A might be better than laboratory B for a more consistent and a more robust test result,” Bloom said.

“That would be the single biggest thing that I would tell oncologists to do,” he noted. “You need to become partners with a local pathologist, even if your local pathology lab doesn’t perform the test.”

Top Tests Available at Clarient

Combining innovative diagnostic technologies with world-class pathology expertise, Clarient's state-of-the-art laboratories provide advanced oncology testing and diagnostic services to assess and characterize cancer. Using a wide range of methodologies, including flow cytometry, IHC, ISH, FISH, cytogenic karotyping, immunofluorescence, microarray, and molecular testing, these are the 7 leading tests Clarient performs:

Mammostrat Breast Recurrence Assay

Methodology: Immunohistochemistry

Highlights:

• Mammostrat is a novel test for estimating the risk for recurrence in hormonereceptor positive, early-stage breast cancer.
• Mammostrat stratifies breast cancer patients into low risk (patients have a 7.6% chance of distant recurrence over a 10-year period); moderate risk (patients have a 16.3% chance of distant recurrence over a 10-year period), and high risk (patients have a 20.9% chance of distant recurrence over a 10-year period).

ALK Rearrangement

Methodology: FISH

Highlights:

• ALK mutations have been identified in 3% to 7% of patients with non-small cell lung cancer (NSCLC).
• The presence of ALK gene rearrangements may help treating physicians select more effective therapies for patients with NSCLC.
• ALK gene rearrangements define a distinct molecular subset of NSCLC that is mutually exclusive from EGFR and KRAS mutations.
• The FISH test results should be used in conjunction with other clinical information.

BRAF

Methodology: Real-time polymerase chain reaction

Highlights:

• BRAF mutations account for approximately 12% to 15% of colorectal cancer cases.
• BRAF mutations are biomarkers of nonresponse to anti-EGFR therapies.
• BRAF mutations are highly predictive of nonresponse to therapy with cetuximab or panitumumab in combination with chemotherapy and as monotherapy.

BRAF V600 Mutation

Methodology: Real-time polymerase chain reaction

Highlights:

• Approximately 60% of melanomas harbor activating mutations in BRAF V600E as identified by the cobas 4800 test.
• The cobas 4800 test is the first FDA-approved diagnostic test to help identify patients with the BRAF V600E mutation.
• Patients with BRAF V600 mutation-positive melanoma as detected by the cobas 4800 test showed dramatic results with vemurafenib.

EGFR Mutation Analysis

Methodology: Molecular polymerase chain reaction

Highlights:

• EGFR mutations can be seen in approximately 10% to 15% of patients.
• The development of selective tyrosine kinase inhibitors is an important area of drug discovery for the treatment of a variety of solid tumors such as breast, ovarian, and colorectal cancers, NSCLC, and carcinoma of the head and neck.
• Patients with EGFR mutations respond more favorably to EGFR tyrosine kinase inhibitors than non-mutation carriers.

KRAS Mutation Analysis

Methodology: Real-time polymerase chain reaction

Highlights:

• KRAS mutations can be detected in approximately 30% to 40% of patients with colon cancer.
• Patients with wild-type KRAS have shown much greater benefit to anti-EGFR therapies.
• Identification of mutations along the KRAS gene suggests that anti-EGFR therapies will not be efficacious in most patients.

PI3K

Methodology: Molecular polymerase chain reaction

Highlights:

• The PI3K pathway plays an important role in many cancers, including colorectal, breast, and lung cancers.
• The presence of activating mutations in the PIK3CA gene, which encodes PI3K, can occur in 20% to 30% of cases.

Source: Clarient Inc's website www.clarient.com.