Cetuximab Plus Chemotherapy May Improve Colorectal Cancer Outcomes

Cetuximab (Erbitux) plus chemotherapy showed higher progression-free survival (PFS) and overall survival (OS) for patients with metastatic colorectal cancer (mCRC), according to one study.

When combined with chemotherapy, cetuximab shows promising efficacy for optimizing treatment strategies for patients with metastatic colorectal cancer (mCRC). | Image credit: Chinnapong - stock.adobe.com

These findings offer valuable insights for optimizing mCRC treatment strategies. The systemic and meta-analysis was published in BMC Cancer.

“Monoclonal antibodies are effective therapeutic options in mCRC treatment,” wrote the researchers of the study. “Cetuximab, an anti-EGFR monoclonal antibody, demonstrated a significant advancement in managing mCRC when combined with various chemotherapy regimens. When used in conjunction with chemotherapy, cetuximab had a better prognosis for patients with CRC who had metastases by improving both overall and progression-free survival.”

Cetuximab was approved in 2004 to treat patients with advanced CRC that has spread to other parts of the body, making it the first monoclonal antibody approved to treat this type of cancer.² In December 2024, the FDA approved encorafenib with cetuximab and mFOLFOX6 for mCRC with BRAF V600E mutation, based on BREAKWATER trial (NCT04607421) results.³

In this study, the researchers searched PubMed and Google Scholar for studies on mCRC treatment with anti-EGFR therapy.¹ Primary outcomes included PFS and OS, standardized across studies. Data extraction was independently conducted by 2 reviewers, with discrepancies resolved through discussion. Study quality was assessed using the Newcastle–Ottawa Scale. Statistical analysis employed fixed- or random-effects models based on heterogeneity, with subgroup analysis and funnel plots used to assess bias.

A total of 25 studies were included in the analysis, with 3788 patients with mCRC, aged 18 to 77 years. Patients receiving cetuximab plus chemotherapy showed significantly improved PFS (HR, 0.79; 95% CI, 0.63–0.96, P < .01, I² = 38%) and OS (HR, 0.78; 95% CI, 0.60–0.91, P < .01, I² = 47%) compared with controls. Subgroup analysis of randomized controlled trials confirmed these benefits, with consistent HRs for PFS (HR, 0.77; 95% CI, 0.62–0.93) and OS (HR, 0.76; 95% CI, 0.61–0.88), reinforcing cetuximab’s efficacy.

However, the researchers noted some limitations. First, small sample sizes in some studies may have influenced outcomes, and the inclusion of both retrospective and prospective studies could impact result accuracy. Second, methodological differences—such as study design, patient characteristics, treatment protocols, and follow-up periods—contributed to heterogeneity. Third, restricting the analysis to English-language publications introduces potential publication bias. Lastly, the findings relied on HRs, but not all studies reported these with corresponding confidence intervals, particularly for OS, which may have affected result reliability.

Despite these findings, the researchers believe the study demonstrated significant benefits of combining cetuximab with chemotherapy for patients with mCRC.

“The cetuximab-based therapy is associated with a substantial improvement in progression-free survival and overall survival compared to chemotherapy alone,” wrote the researchers. “Our meta-analysis justifies the useful addition of cetuximab to standard chemotherapy regimens for mCRC. This approach could improve patient outcomes and provide a valuable addition to current treatment strategies. Future research is needed to confirm its clinical efficacy, identify patient subgroups that are most likely to benefit and explore its impact on survival and quality of life for optimal integration into clinical practice. The findings underscore the cetuximab-chemotherapy combination as a promising first-line protocol for mCRC.”

References

1. Azeem, M, Rehman, A, Rasheed, S, et al. The impact of combining cetuximab with the traditional chemotherapy regimens on clinical effectiveness in metastatic colorectal cancer: a systematic review and meta-analysis. BMC Cancer 25, 331 (2025). https://doi.org/10.1186/s12885-025-13515-3

2. Information on cetuximab (marketed as Erbitux). FDA. Updated July 9, 2015. Accessed February 26, 2025. https://www.fda.gov/drugs/postmarket-drug-safety-information-patients-and-providers/information-cetuximab-marketed-erbitux

3. Bonavitacola J. FDA approves encorafenib with cetuximab and mFOLFOX6 for metastatic CRC. AJMC®. December 20, 2024. Accessed February 26, 2025. https://www.ajmc.com/view/fda-approves-encorafenib-with-cetuximab-and-mfolfox6-for-metastatic-crc