Precision Medicine Program

The rapidly evolving field of precision medicine shows great promise in
the treatment, early detection, and risk management of cancer. Cancer is driven by gene abnormalities – mutations, rearrangements, deletions, amplifications – that alter cell behavior and cause malignancies. As the understanding of the cancer genome advances, along with further development of molecularly targeted drugs, physicians’ ability to select the most effective treatment for each patient’s tumor based on its molecular profile is improved. The Precision Medicine Program was launched at Hoag in 2016, positioning Hoag Family Cancer Institute on the leading edge of precision medicine clinical implementation and research.

Michael Demeure, M.D., M.B.A., F.A.C.S., F.A.C.E., was recruited to Hoag in 2017 to lead the Precision Medicine Program. Prior to joining Hoag, Dr. Demeure led an active research lab for over 20 years, focusing his efforts on the use of genomic technologies to develop novel biomarkers, new therapeutic targets, and related therapies in the management of endocrine and gastrointestinal cancers. Dr. Demeure is joined by molecular pathologist, David Braxton, M.D., Carole Norman, R.N., precision medicine program manager, variant scientist and educator, Sourat Darabi, Ph.D., medical geneticist, Valentina Dalili-Shoaie, M.D., genetic counselors, Jeanne Homer, M.S., Frances Oh, M.S., Chelsey Weatherill, M.S., and additional leadership from Burton Eisenberg, M.D., executive medical director of Hoag Family Cancer Institute and Grace E. Hoag Executive Medical Director Endowed Chair.

HOAG FAMILY CANCER INSTITUTE’S PRECISION MEDICINE PROGRAM FOCUSES ON THREE AREAS:

Tumor Profiling

Technology for genetic profiling of cancers has become increasingly sophisticated while the cost of profiling has decreased dramatically. Hoag Family Cancer Institute collaborates with Caris Life Sciences and other commercial labs for profiling and bioinformatic analysis. Our guiding priority is to profile patients with metastatic disease whose tumors have not responded to standard therapy to discover opportunities for clinical trials or an alternate treatment approach. These results are often discussed in disease site specific tumor boards. A monthly molecular tumor board highlights interesting and unique patient tumor genomic results.

In certain cancers, notably lung cancer, tumor profiling has become standard practice before beginning chemotherapy. A patient whose non-small cell lung cancer has an ALK fusion, for example, will have a better response to a drug that targets the abnormal ALK protein than they would to chemotherapy and will experience fewer adverse side effects. Beginning in 2016, Hoag Family Cancer Institute incorporated tumor profiling as the standard for patients with advanced cancer within several of the Institute’s multidisciplinary site-specific cancer programs.

All patients diagnosed with lung cancer (stage 1b or greater) whose biopsies are performed at Hoag receive tumor profiling through Caris Life Sciences’ Molecular Intelligence® panel of over 600 cancer genes. Caris provides a detailed report that includes relevant biomarkers, drug response prediction – both beneficial and non-beneficial, mutation load, clinical trials for which the patient may be eligible, and level of evidence associated with each biomarker gene association.


"Hoag's Precision Medicine Program has allowed me to provide treatment tailored to both the patient and the tumor. DNA is the key to targeted anti-cancer therapies. The program has given me the knowledge to predict which treatments will have the highest chance of success and improve my patients’ outcome.""
-George Semeniuk, M.D.
Medical Oncologist

Hoag patients with lung cancer have had their tumors profiled since the initiative launched in late 2016. The Head & Neck Cancer Program and GYN Oncology Program have also incorporated consistent tumor profiling. A discussion of patients’ results and how it may affect their treatment course are incorporated in each program’s tumor board meeting.

The Precision Medicine team of experts at Hoag reviews the results of each patient’s tumor profiling to evaluate the findings and offer additional insights and guidance to treating oncology physicians. Hoag’s molecular pathologist, one of only three in the entire Providence Health system, adds an extra level of expertise to the program. The team stays current on the ever-changing molecular testing technology, drug-gene associations and clinical trials with new cancer drugs in order to serve as a resource to clinicians.

Through Hoag’s partnerships with Caris Life Sciences and Syapse, a software platform for precision medicine, Hoag can access and contribute to two robust databases of patient tumor molecular profile results and targeted treatment outcomes. The information includes data from leading cancer centers at major academic research facilities across the United States that are also members of these precision medicine networks.

Collaboration with Hereditary Cancer Program and High-Risk Cancer Programs

While historically there has been a large focus on hereditary cancer screening for breast and ovarian cancer, recent recognition of other relevant germline genetic mutations indicating an increased risk for other cancers has led to an increased role for germline testing. In collaboration with the Precision Medicine Program, the Hereditary Cancer Program’s testing for cancers other than breast and ovarian is steadily increasing.


"At Hoag, we work together relentlessly to dissect the inner workings of cancer cells. As a result of the Precision Medicine Program, we keep getting closer to more effective treatments with less side effects."
N. Simon Tchekmedyian, M.D.
Medical Oncologist

Hoag’s Precision Medicine team, in an effort lead by our molecular pathologist, Dr. David Braxton, reviews each Caris report in order to identify mutations that could be related to germline genetics so that appropriate patients can be referred to genetic testing through Hoag’s Hereditary Cancer Program. In nearly half of cases, germline testing reveals mutations in unsuspected genes not necessarily related to the patient’s primary cancer. Of course, germline mutation screening is also critical in the identification of family members who could be at increased risk for cancer. Patients and family members identified may be referred to one of Hoag Family Cancer Institute’s cancer specific high risk or screening programs for ongoing tumor surveillance, early detection or intervention. They may also be referred to the program’s board-certified medical geneticist.

Another unique program developed by Hoag’s Precision Medicine and Hereditary Cancer teams is the initiation of a clinical research study using whole-body MRI screening for patients who have a germline TP53 mutation, or Li-Fraumeni Syndrome, identified through genetic testing. Individuals who carry a germline TP53 mutation are predisposed to many different cancers including brain tumors, lung cancer, sarcoma, adrenal cancer, leukemia, and breast cancer. To date, there is no consensus or guidelines on how these patients should best be monitored. Through this MRI screening study, the hope is to enable identification of cancers at an early stage when they are most treatable.


"I applaud Hoag for embracing state-of-the-art precision medicine for its patients. It has afforded me the opportunity of tailoring diagnoses to the individual characteristics of each patient and his or her disease. Hoag patients can now expect not only more accurate diagnoses, but increased treatment options including clinical trials. Precision medicine allows me to practice at the forefront of cancer research."
Janet Stallman, M.D.
Pathologist

Resource to Hoag’s Medical Oncology Community

Precision medicine and genomics are advancing rapidly and changing the landscape of cancer care. While the potential benefit to patients is vast, the challenge for oncologists lies in making sense of an overwhelming amount of new information – information they were not likely introduced to in medical school – and appropriately putting it to use all while maintaining busy clinical practices. The Precision Medicine Program intends to partner with Hoag’s medical oncologists in digesting the copious amounts of new and changing genomic information. Dr. Demeure, Dr. Darabi and the team participate in tumor boards in order to present and interpret relevant genomic information, facilitate lectures and presentations from experts in the field, and are available as a resource to consult on the selection of appropriate tumor profiling panels, interpretation
of results and the evaluation of treatment options.

INNOVATION AND CLINICAL RESEARCH

The newness of precision medicine approaches warrants demonstration of clinical utility, which means it is being used by doctors to guide care and it is helping patients achieve better outcomes. Hoag’s Precision Medicine Program participates in several multicenter research studies and initiates its own research studies.

One such pilot research study is in pharmacogenetics. One’s genes affect how one metabolizes drugs, how effective some drugs may be and whether the individual may have an increased risk of an adverse reaction to a drug. The FDA has identified over 100 such drug-gene associations involving 22 genes. Genetic testing for inherent genetic differences can pinpoint a patient’s response to various medications. The information can help doctors select and appropriately dose certain drugs. It is also hoped that this process can be a major factor in decreasing toxicity and hospitalization from adverse drug reactions. Hoag’s study will accrue 50 patients whose DNA obtained from oral swabs is sent to a commercial lab for a 22 gene panel test. Their clinical and pharmacy history is then analyzed with the genetic results. Hoag’s study is testing the hypothesis that genetic analysis will demonstrate at least 30% of patients are currently taking a drug for which there is a pharmacogenetics cautionary variant. Secondary aims are to demonstrate feasibility and identify opportunities for integration into routine care.

Precision Medicine Clinical Research Studies:


135-17 Caris Molecular Intelligence® and Caris Centers of Excellence for Precision Medicine Network™ Outcomes Associated Repository


136-17 Caris Molecular Intelligence® and Caris Centers of Excellence for Precision Medicine Retrospective Outcomes-Associated Database


167-17 Caris ctDNA Validation Project


179-17 Pharmacogenetics Program Pilot program to assess the potential role of pharmacogenomics to improve drug safety in patients with advanced cancer.


204-17 Advance Treatment of Rare Tumors (tumor and normal tissue collection for gene expression array, CGH, NGS, and blood for NGS testing)


101-18: Registry of patients in kindreds with germ-line TP53 mutations (Li-Fraumeni)

For an up to date list of open clinical trials, contact Leila Andres, M.S., at 888-862-5318.


""Hoag’s Precision Medicine Program has allowed us to identify rare, actionable lung cancer mutations, such as HER-2 and EGFR Exon 20 insertion mutations, that confer resistance to both traditional chemotherapies and even newer immunotherapies. In turn, patients from our local community and around the world come to Hoag to benefit from clinical trial drugs specifically targeting these and other lung cancer driver mutations."
Nishan Tchekmedyian, M.D.
Medical Oncologist

For more information call: 949-722-6237