With Robust Molecular Tumor Registry "MrT," The Stars Align
Wrestling with “next generation sequencing," this Mr. T is helping Duke oncologists utilize a Molecular Tumor Board to deliver patient centered precision cancer medicine
targeted therapies block the growth and spread of cancer by interfering with specific molecular targets on those tumors that are involved in the growth, progression and spread of cancer.Some of the newest and most exciting cancer drugs target tumors that have a specific genetic mutation or characteristic. These
As more and more of these targeted therapies come to market, and as older targeted therapies are approved for new indications, oncologists have been ordering comprehensive genomic profiling tests (also called next-generation sequencing or NGS) for an increasing number of their patients with metastatic cancer.
NGS testing is possible from tumor tissue or routine blood draw, and which type of NGS test is ordered depends on many factors including disease type and individual patient circumstances.
Testing is almost exclusively, however, used to guide management of patients with advanced cancer and in later stages of therapy.
Right on Target with "MrT"
Precision cancer medicine is a high priority initiative in Duke Cancer Institute’s strategic plan. Two years ago, DCI partnered with the Department of Pathology and DUHS Clinical Laboratories on a groundbreaking Precision Cancer Medicine Initiative (PCMI).
The initiative’s four faculty leaders John Strickler, MD (Solid Tumors); Matthew McKinney, MD (Hematologic Malignancies); Michael Datto, MD (Molecular Diagnostics and DUHS Clinical Laboratories); and Shannon McCall, MD (PCMI Research Initiatives) are maximizing the organization, availability, and interoperability of cancer patients’ clinical and tumor genomic information for the benefit of cancer care and research with an increasingly active weekly Molecular Tumor Board (MTB) and a growing Molecular Registry of Tumors.
For patients with “solid tumors,” such as colon cancer, breast cancer, or lung cancer, a screen for as many as 400 genomic alterations is critical, explained Strickler. These genomic tests, he said, might identify a rare "needle in the haystack" that predicts extraordinary response to novel therapies, or identify patients who would benefit from immunotherapy. With the aid of this testing, patients with advanced cancer can avoid toxic treatments with limited benefit, and potentially identify non-toxic therapies with extraordinary benefit.
When tumor tissue is either not available or the tumor’s mutations have “evolved” in response to treatment, a liquid biopsy can screen for up to 73 clinically relevant genomic alterations.
With rapidly evolving cancer breakthroughs and diagnostic technology, all of this testing requires a strategic partnership with leading private diagnostics companies. The MTB team has identified the most innovative and reliable partners to bring cutting edge NGS testing to Duke patients.
As the test results come back to the ordering physicians, they’re inputted into the Molecular Registry of Tumors, nicknamed “MrT” by Datto, who, with DUHS clinical informatics architect Chris Hubbard, designed, built and coded the secure electronic registry. Datto hoped it would be a “robust entity” like Mr. T from the 1980s action-adventure A-Team TV series. And it has already delivered.
Since 2014, Duke had been receiving patients’ NGS reports from the diagnostic companies via printed PDFs that had to be scanned into the patients’ health records. But once Datto asked for and got access to the individual structured data contained in the reports, MrT was off and running.
“It seems relatively simple, but it’s kind of revolutionary,” said genetics scientist Michelle Green, PhD, who left the diagnostic testing industry just a few months ago to assume the newly-created role of Molecular Tumor Board program leader. “This is real-world data with the potential to drive outcomes now. We couldn’t do this before because all the data was stuck in the PDF.”
Each week, Green, along with Strickler, McKinney, and others review the 30 to 40 NGS reports as they come in. Green also reads the daily FDA alerts and keeps up with the latest precision medicine research.
“We may find something unusual in a NGS report that leads to a therapy that’s already FDA approved,” said Strickler. “Or it could be that we find something in the report that helps a clinician find a personalized treatment, or even qualifies the patient for a trial. Additionally, in some cases we have found mutations that may have been inherited, and in those cases we advise referral to a genetic counselor.”
In some cases, patients have received NGS tests, only to learn later that a gene that was thought to be “undruggable” now has an exciting new therapeutic option. MrT allows the MTB to analyze results from the past five years and send “real-time” alerts to physicians when new treatment options become available for their patients.
This extra layer of support that Green and her colleagues provide is of great benefit to oncologists.
“People are discovering new things all the time and for a physician to try and keep up with that while also treating patients can be overwhelming,” said Green. “They have to be able to make the connection to put the data together at the right time, in the right place, for the right patient. Essentially, the stars have to align.”
That's A Match
In the few short months she’s been on staff, Green’s already sent out two batches of what she calls “therapy notifications” to providers whose patients might benefit from a particular therapy based on their NGS test results. She includes a list of providers' affected patients along with relevant links to information about the drug, including the FDA approval announcement and prescribing information.
In April she sent a therapy notification to four providers overseeing the care of eight metastatic or advanced urothelial carcinoma patients with a less common mutation (FGFR3 mutation or an FGFR2/3 fusion) that could potentially benefit from erdafitinib, which had just been granted accelerated approval by the FDA.
In May, she sent out another therapy notification, this time to 11 providers overseeing the care of 50 metastatic breast cancer patients who could potentially benefit from a newly approved drug alpelisib. That drug, when taken in combination with fulvestrant, was found in trials to significantly prolong progression-free survival in post-menopausal women and men with HR-positive, HER2-negative, PIK3CA-mutated advanced breast cancer for whom hormonal therapy stopped working.
Nearly one-third of those 50 are under the care of breast oncologist P. Kelly Marcom, MD.
"As new treatments are approved, clinicians need an infrastructure for managing and acting on complex data so that we do not miss therapeutic options for patients," said Marcom, who directs DCI's Breast Cancer disease group. "The MTB is taking a proactive approach to providing this infrastructure that will both help our patients and also foster new insights and discoveries for cancer treatment.”
Medical oncologist Tian Zhang, MD, MHS, who treats genitourinary cancer patients, called matching patients with newly available molecularly targeted therapies "imperative."
“When erdafitinib was approved for a selected subset of urothelial patients, the MTB sent timely notifications to treating oncologists, including myself — allowing us to reach out to our patients to further discuss treatment options," she said.
McCall noted that since the Molecular Tumor Board started meeting, they’ve analyzed results from over 1,500 patients.
“These patients were offered therapies that they wouldn’t necessarily have gotten offered if we hadn’t been able to track all this data,” she said.
Green and the team are just getting started.
Green has graphed “impressive progress” in the number of outside NGS reports ordered for patients being seen at Duke Cancer Center Durham, Duke Cancer Center Raleigh, Duke Women’s Cancer Care Raleigh, and Duke Cancer Center North Durham since 2014. Those reports — nearly 3,000 — are already in MrT. Myeloid genomic testing data, drawn from an in-house test for 50 different genes commonly mutated in blood cancers, will soon be added to MrT.
“These numbers are only going to get bigger,” said Green, who shared that the team is also very close to adding a clinical trial matching feature to MrT. “We want physicians and patients to know that we offer these services at Duke.”
Information on the Precision Cancer Medicine Initiative, the MTB and MrT can be found here. The Molecular Tumor Board meets most Mondays in the GI clinic conference room from 11:30 a.m. to 12:30 p.m. Lunch is served at the meeting. Duke providers, researchers and trainees with questions about accessing MrT are encouraged to contact Michelle Green, PhD.