Colorectal cancer is the second leading cause of cancer-related mortality worldwide with a poor 5-year survival rate in patients with metastatic colorectal cancer. Patients with metastatic colorectal cancer treated with first-line standard-of-care chemotherapy have shown to have poor outcomes.

Now, results from a new study published in the Journal of Clinical Oncology reveal that a combination of Nivolumab plus low-dose ipilimumab, two immune therapeutic agents approved in refractory microsatellite high cancers, were used for the first time in newly diagnosed MSI H metastatic colorectal cancer and demonstrated robust and durable clinical benefit and was very well tolerated as a first-line treatment for metastatic colorectal cancer.

“The data suggests that Nivolumab plus low dose ipilimumab combination has very promising activity in newly diagnosed colon cancer which are characterized with microsatellite instability,” says study author Dr. Heinz-Josef Lenz, associate director for clinical research at the USC Norris Comprehensive Cancer Center (USC Norris). “As a result of this study, this regimen is being included into the NCCN guidelines as a new treatment option for colon cancer.”

Patients were enrolled in this phase II clinical trial between December 2016 through October 2017. At data cutoff, which occurred in October 2019, 45 patients with microsatellite instability-high/mismatch repair-deficient metastatic colorectal cancer who had not received prior therapy for metastatic disease were treated. Among 43 response-evaluable patients, 84% had a reduction in tumor burden and 13% had complete remission of their disease. Most of these patients experienced a deepening of response with a longer follow-up of 29 months. While off treatment, further tumor shrinkage was observed in some patients.

Ryan D’Cunha, a colon cancer survivor and trial participant, was one of the trial participants that had complete resolution of his cancer when it was removed with curative surgery. After receiving a diagnosis of stage four colon cancer, Ryan’s pathology results came back indicating that his cancer was MSI-High, qualifying him for enrollment into the trial with immunotherapy instead of chemotherapy for newly diagnosed metastatic colon cancer. Following 6 months of treatment, the tumor was shrinking allowing Ryan to undergo surgery to remove his cancer in the colon and liver. He did tolerate the immunotherapy very well which has much fewer side effects than chemotherapy. At his post-operative appointment, Dr. Lenz informed Ryan that all tumors had disappeared in the colon and liver demonstrating a complete response to the treatment. He has now been cancer free for four years.

“Cancer has exposed us to the harsh realities of battling a life-threatening illness,” said Ryan D’Cunha. “We are truly blessed to be in the hands of one of the best medical teams in the world. We are also very grateful for the medical advances made possible by dedicated cancer researchers around the world giving us HOPE for the future, instead of fear.”

This combination represents a novel first-line treatment option for patients with metastatic colorectal cancer.  

About this study:

In addition to Dr. Heinz-Josef Lenz, other authors include Eric Van Cutsem MD, PhD, University Hospitals Gasthuisberg/Leuven and KU Leuven; Maria Luisa Limon MD, Hospital Universitario Virgen del Rocio; Ka Yeung Mark Wong PhD, Westmead Hospital; Alain Hendlisz MD, PhD, Institut Jules Bordet; Massimo Aglietta MD, PhD, University of Torino and Candiolo Cancer Center; Pilar García-Alfonso MD, Hospital Gral Universitario Gregorio Marañon; Bart Neyns MD, PhD, Universitair Ziekenhuis Brussel; Gabriele Luppi MD, University Hospital of Modena; Dana B. Cardin MD, Ingram Cancer Center; Tomislav Dragovich MD, PhD, Banner MD Anderson Cancer Center; Usman Shah MD, Lehigh Valley Cancer Institute; Sandzhar Abdullaev MD, PhD, Bristol Myers Squibb; Joseph Gricar MS, Bristol Myers Squibb; Jean-Marie Ledeine MS, Bristol Myers Squibb; Michael James Overman MD, The University of Texas MD Anderson Cancer Center; and Sara Lonardi MD, Istituto Oncologico Veneto IOV-IRCSS. 

About USC Norris Comprehensive Cancer Center

At the USC Norris Comprehensive Cancer Center, more than 250 dedicated physicians and scientists are leading the fight to make cancer a disease of the past. As one of the eight original National Cancer Institute-designated Comprehensive Cancer Centers in the United States, USC Norris has revolutionized cancer research, treatment, and prevention for nearly 50 years. Multidisciplinary teams provide the latest evidence-based care at USC Norris Cancer Hospital, a 60-bed hospital, as well as outpatient clinics throughout Los Angeles and Orange counties.

For more information, visit https://uscnorriscancer.usc.edu.