Colorectal cancer is the third most common cancer diagnosed in both men and women in the United States (skin cancer aside). The American Cancer Society anticipates 95,270 new cases of colon cancer in 2016 and more than 49,000 deaths from the disease.
Fortunately, death rates tied to colon cancer are actually on the decline thanks to increased awareness, earlier screenings and advances in medical therapies. Those breakthroughs were highlighted during the annual American Society of Clinical Oncology (ASCO) conference in June. Oncologist Johanna Bendell, MD, director of the GI Cancer Research Program and associate director of the Drug Development Program at Sarah Cannon Research Institute, said findings presented at ASCO would be a game changer for oncologists and colon cancer patients.
Immunotherapy
The most promising news in the treatment of colon cancer revolves around immunotherapy, or using the body’s own system to attack cancer. Bendell said patients with microsatellite instable metastatic colon cancer could derive the greatest benefit from immunotherapy.
What is Microsatellite Instability?
MSI is a change that occurs in the DNA of certain cells, such as tumor cells, in which the number of repeats of microsatellites (short, repeated sequences of DNA) is different than the number of repeats that was in the DNA when it was inherited. According to the National Cancer Institute, the cause of microsatellite instability may be a defect in the ability to repair mistakes made when DNA is copied in the cell.
Approximately 15 percent of MSI patients also have hereditary nonpolyposis colorectal cancer (HNPCC), or Lynch Syndrome. HNPCC is a genetic condition that can encourage growth of additional cancers through the GI tract, making treatment even more critical for the MSI population. Bendell said 25-50 percent of MSI patients studied have shown an incredible response to immunotherapy. While patients with MSI represent only five percent of overall metastatic colorectal cancer cases, Bendell urges gastroenterologists to test all cancer patients for MSI. “In my practice that’s the first question I ask,” she said.
Non-MSI Patients
What about the 95 percent of patients without microsatellite instability?
During the June ASCO conference, Bendell and her colleagues presented data on the use of MEK inhibitory drugs, already approved by the FDA for treatment of melanoma. When used in non-MSI patients, the drug can increase T-cell production and essentially rev up the immune system, triggering a similar response as MSI patients to immunotherapy.
Twenty percent of non-MSI patients who received a combination of MEK inhibitors and immunotherapy responded to treatment. That means a 20-30 percent response rate to immunotherapy across the colon cancer population.
“The next big question in drug development is, ‘How can we make more people respond to immunotherapy?’” said Bendell, who’s been involved in the trial for two years. “Our presentation was just the beginning of the wave examining this treatment.”
Next generation immunotherapy trials are now underway to examine the use of other agents in combination with immunotherapy. The data is so promising that a randomized study has begun for FDA approval, with the first trial sites already opening.
Left or Right?
Doctors have long known that patients with left-sided metastatic colon cancers live longer than those with right-sided, and now researchers are beginning to learn why. “We used to think it was because we caught them earlier because they become symptomatic sooner, but now we see there are biologic distinctions between tumors on the left and right sides,” said Bendell, who noted that patients with left-sided colon cancer often live 15 months longer than those with right-sided.
Typically, right-sided colon cancers carry the BRAF mutation and have hyper-methylation, which carries a poor prognosis. Recent microbiology studies also show different bacteria present in left and right sides can affect the molecular profile of the area of the colon where the bacteria live.
“We think that bacteria has a role in a tumor’s molecular profile, and data presented from a large study of chemo using two different target agents has led to a discussion of the optimal first line treatment for colon cancer,” Bendell explained. “We saw that for patients with right-sided colon cancer they did not appear to benefit at all from the use of a certain treatment. Should we use one chemo agent over another depending on the side affected?”
What Providers Can Do
While researchers await that answer, Bendell encouraged providers to note each patient’s micro stability status, BRAF status, expanded RAS testing, and the side of colon affected, as every piece of information could prove helpful for future treatment. She also encouraged primary care providers to take an aggressive approach in monitoring and examining patients of all ages with persistent GI symptoms, as doctors are seeing a rise in the development of colon cancers among the younger patient population.
“This is all super exciting news in the treatment of colon cancer and is setting the stage for how research in colon cancer will keep moving forward,” Bendell said of recent advances.
RELATED LINKS:
