Nearly every major hospital or cancer treatment practice performs specific genomic testing on every cancer patient’s tumor sample — such as K-ras oncogene analysis for those with colorectal cancer or HER2 analysis in breast cancer. These standard-of-care tests detect a single genetic mutation associated with a patient’s tumor type. Since August, oncologists at Cleveland Clinic’s Taussig Cancer Institute have been enrolling patients in an expanded genomic testing clinical study in which 250 patients with 15 different tumor types will be analyzed over the next year for 236 cancer-related genes.
The genes tested have been implicated in cancer, with implications for cancer therapeutics. They are all included in the FoundationOne™ genomics assessment test. For this clinical investigation, Cleveland Clinic has partnered with FoundationOne’s developer, Foundation Medicine, a molecular information company specializing in comprehensive genomic analysis of tumors.
In the study, each patient’s tumor sample is tested with the FoundationOne genomics profile, which detects several types of DNA alterations — base substitutions, small insertions/deletions, copy number alterations and gene rearrangements. The test includes those genes that show a high frequency of common alterations but also those on a tail on the curve, such as those mutations occurring at low frequency but across many different tumor types. This type of approach provides a strong rationale for looking broadly rather than just looking with disease-specific genes.
“We have chosen a variety of cancers that include the most common cancers,” says Davendra Sohal, MD, MPH, staff physician in the Department of Solid Tumor Oncology and principal investigator of the study. “The goal is to see if this type of expanded genomic testing can impact clinical outcomes in a meaningful way.”
“We understand the importance of genomic testing in a broad fashion and are investing heavily in this,” adds Brian J. Bolwell, MD, FACP, Chairman of the Taussig Cancer Institute. The target population for the study includes patients lacking good treatment options, such as those with metastatic disease or whose cancer has progressed despite one or two rounds of standard chemotherapy. “There is opportunity to make a difference for these people if we can apply the existing knowledge about cancer mutations to making useful treatment decisions.”
FEASIBILITY AND UTILITY
One of the trial’s goals is to study the feasibility of doing genomic analyses in a real-world setting. “We want to see how well tests like FoundationOne can be performed in a real-world setting in a variety of tumors,” comments Dr. Sohal. Questions to be answered include: How long does it take for a patient to be consented to receive this testing? How long does it take to process the test and for doctors at Cleveland Clinic to get the result? How long does it take for the patient to learn the result and recommendations for treatment?
The ultimate goal is to probe the clinical usefulness of expanded genomic testing. Every test result includes molecular details about a patient’s tumor along with supporting data suggesting a particular targeted therapy. This information is provided to a panel of oncologists within the Taussig Cancer Institute. This Genomics Tumor Board meets weekly to review each result independently and make recommendations for treatment — whether with approved drugs or as part of clinical trials in and around Cleveland. These recommendations are transmitted to the primary oncologist, who makes final personalized recommendations to the patient. “If many patients can get to useful treatments — whether FDA approved or off-label, or under a clinical trial of a targeted therapy — then it can make a real difference,” says Dr. Sohal.
Because the science behind genomic testing is evolving rapidly, new genetic mutations are rapidly emerging. Cleveland Clinic has chosen to partner with Foundation Medicine as the company continually updates its testing panel to keep current with the latest research in cancer related genetics.