Can a Novel Combination Therapy Improve Metastatic Colorectal Cancer Outcomes?

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A novel combination comprising experimental immunotherapy drugs plus chemotherapy may improve survival outcomes in previously treated patients with metastatic colorectal cancer compared to the targeted therapy regorafenib alone. These findings will be presented by Wainberg et al at the 2024 ASCO Annual Meeting (Abstract 3508).


When colorectal cancer metastasizes to other parts of the body, it can be more challenging to treat and often requires a combination of therapies—including surgery, chemotherapy, targeted therapy, and immunotherapy. Although treatment advancements have improved outcomes in metastatic colorectal cancer, conventional treatment options may become ineffective as the disease progresses, necessitating the development of innovative therapeutic approaches.

Study Methods and Results

In a phase Ib/II trial, researchers randomly assigned 112 patients with metastatic colorectal cancer who previously underwent treatment with oxaliplatin and irinotecan-containing regimens to receive either the novel treatment combination comprising of the dual A2a/A2b adenosine receptor agonist etrumadenant, the immune checkpoint inhibitor zimberelimab, and the chemotherapy regimen mFOLFOX-6 ± bevacizumab (EZFB) (n = 75) or regorafenib alone (n = 37). They sought to determine whether the combination therapy could improve outcomes in this patient population.

Compared with those who received regorafenib alone, the patients who received the combination therapy experienced a median progression-free survival of 6.2 months vs 2.1 months and a median overall survival of 19.7 months vs 9.5 months. Additionally, the researchers found that 17.3% of the patients in the combination therapy group presented with partial or complete tumor shrinkage compared with 2.7% of the patients in the regorafenib alone group.


The new research highlighted the potential of combining immune-targeted therapy with traditional chemotherapy to better control colorectal cancer metastasis and enhance treatment effectiveness and outcomes.

"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,” underscored lead study author Zev Wainberg, MD, MSc, Co-Director of the University of California, Los Angeles (UCLA) Health GI Oncology Program and a researcher at the UCLA Jonsson Comprehensive Cancer Center. “These results pave the way for further exploration of this promising treatment approach,” he concluded.

Disclosure: The research in this study was sponsored by Arcus Biosciences. For full disclosures of the study authors, visit

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.