ASCO: Combination Therapy Significantly Improves Outcomes for Patients with Metastatic Colorectal Cancer

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A study led by UCLA Health Jonsson Comprehensive Cancer Center researchers found that using a combination of experimental immunotherapy drugs with chemotherapy significantly improves progression-free survival and overall survival for patients with metastatic colorectal cancer who have previously undergone standard chemotherapy treatment when compared to those who received the targeted therapy regorafenib alone.

The median progression-free survival, which is the amount of time during and after treatment when the cancer does not worsen or progress, with the combination treatment was 6.2 months compared to 2.1 months for those in the targeted therapy only group. 

The median overall survival with the combination treatment was 19.7 months as compared to 9.5 months for those in the targeted therapy only group.

The results of the study also showed treatment with the novel combination therapy either partially or completely shrank tumors in 17.3% of patients. For patients on regorafenib only, 2.7% had tumor shrinkage.


When colorectal cancer starts to spread to other parts of the body, it can be more challenging to treat and often requires a combination of therapies, including surgery, chemotherapy, targeted therapies and immunotherapy. While these advancements in treatment options have improved outcomes for many patients with metastatic colorectal cancer, it still remains a significant health issue. Conventional treatments often become ineffective as the disease progresses, requiring the development of innovative therapeutic approaches. 


This group of investigators looked at evaluating the efficacy of a novel treatment combination, called EZFB, which consists of etrumadenant (E), a dual A2a/A2b adenosine receptor antagonist, zimberelimab (Z), an immune checkpoint inhibitor, and a chemotherapy regimen (FB: mFOLFOX-6 ± bevacizumab), to see if it could improve outcomes for people who were previously treated for this aggressive form of cancer.

The team enrolled 112 participants with metastatic colorectal cancer who had previously undergone treatment with oxaliplatin and irinotecan-containing regimens in the Phase Ib/II trial. The patients were randomized into two groups: 75 receiving the EZFB combination and 37 receiving regorafenib alone.


The study's findings underscore the potential of combining immune-targeted therapy  with traditional chemotherapy to better control the spread of the cancer and enhance the effectiveness of the treatment in metastatic colorectal cancer.

"The improvement in both progression-free survival and overall survival observed with the EZFB combination represents a significant advancement in the management of refractory metastatic colorectal cancer,” said first author of the abstract Dr. Zev Wainberg, co-director of the UCLA Health GI Oncology Program and researcher at the UCLA Health Jonsson Comprehensive Cancer Center. “These results pave the way for further exploration of this promising treatment approach."


The abstract’s senior author is Michael Cecchini from Yale University School of Medicine. Other authors are Sae-Won Han, Soohyeon Lee, Keun-Wook Lee, Scott Kopetz, Jonathan Mizrahi, Yong Sang Hong, François Ghiringhelli, Antoine Italiano, David Tougeron, Brandon Beagle, Mathew Boakye, Tingting Zhao, Joon Rhee and Dimitry Nuyten. 


Wainberg will present the findings (Abstract 3508) at the annual American Society of Clinical Oncology meeting on Sunday, June 2 during the Oral Abstract Session of the Gastrointestinal Cancer—Colorectal and Anal Track from 8 to 11am CT.

The study was sponsored by Arcus Biosciences.

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