Red, orange and yellow colon cancer cell, computer illustration

A New Cancer Treatment Discovery Brings Hope for a Subgroup of Patients Facing Metastatic Colon and Rectal Cancer

Marwan Fakih, M.D., identifies a combination immunotherapy that shows promise in treating advanced colon and rectal patients with a biomarker known as microsatellite stable.

A Foundational Step in Advanced Colorectal Cancer Treatment 

Marwan G. Fakih, M.D.
                              Marwan G. Fakih, M.D.

Marwan Fakih, M.D., a physician-scientist at City of Hope, identified a novel combination immunotherapy regimen that demonstrated significant response in a Phase 1 clinical trial for a subgroup of people with recurrent metastatic colorectal cancer. 

The study, developed and led by City of Hope’s Fakih, enrolled 29 patients with chemotherapy-resistant metastatic colon cancer and rectal cancer who had a biomarker known as microsatellite stable (disease). Each participant received a combination immunotherapy treatment consisting of ipilimumab and nivolumab, plus the targeted therapy regorafenib. Of the 22 patients whose cancer had not yet spread to the liver, more than 50% are still alive after 20 months. The seven patients whose disease had spread to the liver also received the study treatment, but had a less favorable outcome with a median survival of seven months.

“The combination immunotherapy regimen shows remarkable activity in metastatic microsatellite stable patients without liver metastases, a patient population previously regarded as nonresponsive to immunotherapeutic strategies,” said Fakih, co-director of City of Hope’s Gastrointestinal Cancer Program and primary investigator of the clinical trial. “To see a response rate of 40% and median overall survival exceeding 20 months in refractory colorectal cancer without liver metastatic disease patients is unprecedented.” Fakih is a professor in the cancer center’s Department of Medical Oncology & Therapeutics Research and the Judy & Bernard Briskin Distinguished Director of Clinical Research.

Building on Research to Improve Patient Outcomes

In a previous study, Fakih noted there was a modest benefit when treating metastatic colorectal cancer patients without liver disease with nivolumab and regorafenib. Here, he showed that adding a CTLA-4 inhibitor, ipilimumab, appears to improve the health outcome in this subgroup of patients. (In a small sample of patients with liver metastases, the addition of CTLA-4 inhibitors did not appear to lead to major clinical benefits.)

“Our data confirms the importance of the tumor microenvironment in shaping the response to immunotherapy. Patients without liver metastatic disease can respond to a combination of checkpoint inhibitors, plus a small molecule VEGR tyrosine kinase inhibitor, as we have shown with our regimen,” Fakih said.

As a National Cancer Institute-designated comprehensive cancer center, City of Hope is ranked as one of the nation’s top 10 "Best Hospitals" for cancer by U.S. News & World Report, in addition to being recognized as high performing in colorectal cancer surgery and known for their leading-edge colorectal care. Fakih shared that in his daily practice, he works to identify additional treatment options for cancer patients through clinical trials. He is leading a team of researchers at City of Hope who are continuing to explore the role of anti-PD-1/CTLA-4 antibody combinations in microsatellite stable colorectal cancer to help improve patient outcomes.