Genomic Profiling Enhances Treatment Options for Metastatic Colorectal Cancer

Study confirms feasibility, benefits of large-scale cancer genomics in the clinic

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In a study of the impact that genomic profiling has on treatment decisions for individual patients, Cleveland Clinic oncologists and investigators from other institutions found that profiling influenced treatment decisions in one-third of metastatic colorectal cancer patients participating.

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Identifying Actionable Gene Alterations in Colorectal Cancer

Genomic testing for mutations that predict how well patients will respond to standard therapies has become common practice in the treatment of metastatic colorectal cancer (CRC). “Although genome sequencing is used widely in clinical settings, its value to individual patients has not been thoroughly investigated,” says Davendra Sohal, MD, MPH, an oncologist at Cleveland Clinic’s Taussig Cancer Institute. Dr. Sohal and his collaborators conducted a study of outpatient genomic testing to identify the presence of actionable alterations and how this impacted disease management decisions.

“We recruited 45 patients 18 years or older with metastatic colorectal cancer and sequenced tumor samples for up to 315 candidate genes using the FoundationOne™ genomic profile,” says Dr. Sohal.

Cleveland Clinic’s Genomics Tumor Board discussed the results and made therapeutic recommendations. The Board recommended therapy targeting an actionable alteration for 22 of the patients, representing 51 percent of the study group. The Board recommended specific clinical trials for 88 percent of the 22 patients. The study confirmed the feasibility of genomic profiling and its benefit to individual patients.

“The most common reason a patient did not receive the recommended targeted therapy was unavailability of appropriate clinical trials,” Dr. Sohal says.

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Challenges of Genomic Testing

Dr. Sohal also investigated challenges associated with genomic testing in pancreatobiliary (PB) cancers, finding that the scarcity of diagnostic tissue presents a major stumbling block for researching targeted agents in this area. “The research community is becoming aware of this, and newer trials are requiring good tissue specimens, so there is a move toward obtaining bigger specimens from pancreatobiliary cancer patients at the time of diagnosis. This should mitigate this problem,” he says.

Of the PB patients for whom adequate diagnostic tissue was available, the Genomics Tumor Board recommended targeted (either on-study or off-label) therapy to 7 patients, and 78 percent of these recommendations were for specific clinical trials.

The lack of appropriate clinical trials represents the primary reason that patients with a targeted therapy recommendation did not receive treatment. “Most of these cases have gene alterations, such as TP53 and others, for which there are no known drugs. Many patients are so sick, they have trouble going through even the first line of standard chemotherapy,” Dr. Sohal explains.

Outlook for Cancer Genomics

The ultimate purpose of investigating the impact of genomics on therapeutic decisions and disease management is to determine how to use that information in a clinical setting. The scientific and medical community must take action to improve access to clinical trials researching targeted agents for treating CRC, pancreatic cancer and other cancers with a poor prognosis.

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“A concerted effort to improve access to clinical trials is required and underway,” says Dr. Sohal. The American Society of Clinical Oncology, the National Cancer Institute and various pharmaceutical companies, in addition to most cancer researchers, are pursuing trials of therapies that target particular genomic alterations. “A good example of this would be a trial targeting all mutant BRAF tumors as opposed to one that focuses on specific histologies like a drug that targets only colon cancer,” he explains. These trials are still not widely available; Dr. Sohal and other researchers hope access to them will continue to improve.

“Large-scale genomic studies, such as The Cancer Genome Atlas (TCGA), provide big clues for developing targeted therapies. More detailed studies exploring those clues are then required to home in on precise targets within the most promising pathways,” he says. These detailed studies will narrow the gap between knowledge gained from large-scale cancer genomics and its practical application in the clinical setting.

Dr. Sohal presented the findings at the 2015 Gastrointestinal Cancers Symposium.

Photo Credit: ©Russell Lee