Although colon cancer is the fourth most commonly diagnosed cancer in the U.S., roughly two-thirds of patients are diagnosed before their disease has spread, when the prognosis is generally good. These patients undergo surgery and, sometimes, additional treatment, usually chemotherapy.
Up to 30 percent of colon cancers, however, have already spread (metastasized) by the time the patient is diagnosed.
Treatment for metastatic colon cancer
Patients with metastatic colon cancer (stage 4) get intensive chemotherapy, says Paul Oberstein, M.D., director of the gastrointestinal medical oncology program at NYU Langone’s Perlmutter Cancer Center. In this case, chemotherapy doesn’t provide a cure, but does reduce symptoms and helps patients live longer.
“We usually start with a combination of chemotherapy and a targeted therapy, which is determined based on tumor characteristics,” Dr. Oberstein says. “The mutations in the tumor matter very much when it comes to what targeted therapy to give.”
Dr. Oberstein says the location of the tumor—whether it’s on the left or the right side of your colon—also drives decisions about which targeted therapy to give. Your overall health also matters. If you’re on medications for other diseases, for example, some targeted therapies may interact with these drugs.
In general, says Dr. Oberstein, most metastatic colon cancer patients get this combination of chemotherapy and a targeted agent. “It will control the disease and they’ll remain stable for a period of time, on average 6 to 15 months. At some point, they either can’t tolerate the chemotherapy, or the tumor grows despite chemotherapy, and the patients progress on therapy.”
If your tumor continues to grow, your oncologist will try another combination of drugs, which should give you several additional months of disease control. This is second-line therapy. When second-line therapy subsequently fails to control your cancer, you’ll get another combination of drugs (third-line therapy).
“Putting that all together, patients with metastatic colon cancer get multiple lines of chemotherapy and live with their disease for an average of two to three years with the current therapies that we have,” says Dr. Oberstein. “The duration depends to a large extent on the mutations within the tumors (certain mutations predict doing worse or better) and a lot to the health of the patient and how they tolerate chemotherapy.”
Newer treatment options: targeted therapies and immunotherapies
Some tumors have specific molecules that help cancer cells grow, multiply quickly, and spread outside the colon. Targeted therapies are drugs or substances developed specifically to disrupt these molecules so that cancer cells can’t grow or survive. For example, anti-VEGF (vascular endothelial growth factor) targeted drugs limit a tumor’s ability to grow new blood vessels, which bring the tumor nutrients it needs to grow.
Unlike chemotherapy, which kills all fast-growing cells, targeted therapy interrupts the process by which tumor cells grow and spread. When given in conjunction with chemotherapy, some targeted therapies help chemotherapy be more effective. To date, the U.S. Food and Drug Administration (FDA) has approved six targeted therapies for metastatic colon cancer. Not all targeted therapies work in all patients, so treatment is tailored to the unique features of your tumor.
“We’re taking a deep dive into these tumors, looking at the genetics of tumors and using the information to guide therapies,” says Samuel J. Klempner, M.D., a gastrointestinal oncologist at The Angeles Clinic and Research Institute, a Cedars-Sinai affiliate, and assistant professor of Medicine at Cedars-Sinai.
One molecular group of interest is BRAF mutant colon cancers, Dr. Klempner says. “BRAF is a protein. If you mutate it in certain areas, it’s like flipping a switch on all the time. It’s a signal for the tumor cell to grow.”
Targeted therapies for BRAF mutations are small molecule inhibitors, often pills, which get inside the tumor cell and turn off the switch. “The FDA recently approved a combination regimen directed for BRAF in colorectal cancers,” Dr. Klempner says. “This is important because it benefits a group of patients who are not responding well to traditional chemotherapy and is a group that generally does poorly. It’s nice to have something to offer these patients.”
Immunotherapy, on the other hand, stimulates the immune system to fight cancer. Checkpoint inhibitors, for example, disrupt cancer cells’ ability to hide from the immune system. These therapies are being used successfully in other types of cancer, and are starting to be used in colon cancers as well.
For example, about five percent of stage 4 colon cancer patients have specific tumor characteristics called microsatellite high, Dr. Klempner explains. “The tumor has an error in the machinery that repairs mistakes in the DNA. Those types of tumors accumulate thousands of mutations so the immune system is primed to recognize them. When you give immunotherapy, patients tend to have high response rates. Often the response lasts well over a year and the drugs are generally well tolerated.” The FDA has approved three immunotherapies for metastatic colon cancer.
Dr. Klempner says these are good examples of learning what makes tumors tick by studying them in the lab and then developing targeted drugs that translate into improved outcomes for patients. Pathologists now routinely test tumor biopsies to see if patients might be candidates for targeted therapy or immunotherapy.
These therapies are only appropriate for a small subset of patients. Furthermore, they’re costly and the toxicity and side effects are different from chemotherapy side effects. For example, left untreated, a cough or diarrhea in someone undergoing immunotherapy may turn into pneumonitis or colitis (inflammation of the lungs or colon, respectively). Tell your oncologist right away if you experience side effects while taking these drugs.
If you are diagnosed with metastatic colon cancer, ask your oncologist if you qualify for a clinical trial that is evaluating a potential new therapy.