What’s New in Colon Cancer Treatment and Clinical Trials?

March 18, 2021

We recently sat down with Hematologist-Oncologist, Dr. Eduardo Fernandez, of the Sidney Kimmel Cancer Center – Washington Township, to learn how these new colon cancer treatments have come about and how they’ve helped improve outcomes.

Treatments have continued to improve primarily due to the participation of patients in clinical trials, allowing for more personalized treatment, says Dr. Fernandez. Most notable advances are typically made for advanced stage, or metastatic, cancers, and then, through other clinical trials, applied to earlier disease.

How Genetic Testing Has Helped

Genetic testing has been used to identify family members who may be at significantly higher risk for cancer but have not yet developed it. If they are screened more intensely, a cancer can potentially be caught early and cured without the need for chemotherapy or other treatments.

Genetic testing, contrary to popular belief, isn’t only about inherited cancer syndromes, such as Lynch Syndrome or the BRCA-1/2 mutation prominent in breast cancer, explains Dr. Fernandez. “Genetic testing also uncovers the acquired (somatic) mutations that occur later in life and can’t be passed down. They tell us what targeted therapies to focus on.”

New Approaches to Chemotherapy

How chemotherapy works, in general, is it affects the genetic material of both abnormal and normal cells to disrupt their processes, thus causing cancerous cells to succumb to treatment, explains Dr. Fernandez.

In the 1990s, the standard treatment for colon cancer was chemotherapy – specifically, two medications known as 5-FU and Leucovorin – but this has changed rapidly in the past decade. Since then, Irinotecan, Oxaliplatin, and Avastin – have all been incorporated into first-line treatment of metastatic colon cancer. These are used, not to cure, but to control the disease as best as possible.

When a cancer begins to resist all of these treatments separately, the next step is combining everything together, says Dr. Fernandez. For example, Folfiri is a combination of 5-FU, Leucovorin, and Irinotecan.

New Approaches to Targeted Therapy and Immunotherapy

Targeted and immunotherapies are more focused on destroying a specific pathway that enables the cancer to grow.

It is now a standard part of care that once a diagnosis of colon cancer has been made, a biopsy is performed to find specific mutations and determine the most appropriate treatment route, adds Dr. Fernandez. “Mutations can be found through traditional tissue biopsies or liquid biopsies (which have recently grown in popularity), which examine the presence of cancer cells in the blood.”

The genetic mutations related to colon cancer, include: MSI, or Microsatellite Instability; KRAS; NRAS; BRAF; HER2; and NTRK gene fusion. Although these mutations are rare – occurring in 1-10 percent of patients – they do expand the ability to treat and control progressive cancer for a longer period of time.

“What we’ve found out is that the mechanisms and mutations that commonly drive other cancers actually drive colon cancer too,” said Dr. Fernandez. “We’ve been able to implement treatments we know already work, for cancers such as kidney and lung, as part of treatment for colon cancer.”

In patients with Microsatellite Instability, the use of Keytruda as first-line treatment has been approved, as well as the use of Opdivo and Yervoy. For patients with KRAS, NRAS, and BRAF, Cetuximab and Panitumumab have been approved. About 4-10 percent of patients with BRAF may benefit from a combination of Cetuximab and Encorafenib. HER2 is a protein that signals growth to 5-7% of colon cancers. The presence of HER2 allows treatment with Trastuzumab in combination with Pertuzumab or Enbertu.

How these medications are incorporated into treatment depends on what mutation is identified, what prior treatments have been received, the drug’s FDA approved indication, and their potential side effects, continues Dr. Fernandez. “There’s always a potential for side effects, but we do everything we can to work with patients to limit these. Many new targeted therapies are taken by mouth, which allows for better control of side effects and ease of administration.”

Improved Outcomes

If we look back at data from use of 5-FU and Leucovorin, survival rates for metastatic colon cancer were only around 9-12 months. Now, the median survival rate (meaning at least 50 percent of the time) is 2-2½ years.

It is our ultimate goal, as oncologists, adds Dr. Fernandez, to eliminate the development of cancer through chemo; reduce the impact of cancer through screening and uncovering disease early; and identifying new treatments that help us control advanced disease, so patients can live longer, with more manageable side effects (similar to any long-term treatment for other chronic disease, such as diabetes).  

“It is only through diligent research and clinical trials that these goals can be met,” said Dr. Fernandez. The Sidney Kimmel Cancer Center – Jefferson Health in Washington Township is committed to providing patients with the access they need to cutting-edge science.

To learn more about the clinical trials offered through the Sidney Kimmel Cancer Center, click HERE (and scroll down to clinical trials).

For more information on cancer services at the Sidney Kimmel Cancer Center – Washington Township, click HERE or call 856-218-5324.