Monoclonal Antibodies for First-Line Treatment of Metastatic Colorectal Cancer

Background: In addition to discontinuing treatment at disease progression, cumulative toxicity limitations and genetic mutations play important roles in chemotherapy choice in metastatic colorectal cancer (mCRC). However, in recent years, targeted therapies, such as immune checkpoint inhibitors or monoclonal antibodies (MoAbs), have been used with chemotherapy to improve clinical outcomes in patients with mCRC.

Areas of uncertainty: Approximately 15% of patients with CRC would be eligible for further targeted therapy with immune checkpoint inhibitors based on genetic testing, but most patients with CRC would not qualify, especially Kirsten rat sarcoma wild-type. Therefore, adding MoAb is only an option for most patients until disease progression or unacceptable toxicity occurs. However, the results are not consistent with the combination of MoAb and different chemotherapy bases. In addition, most results from combining MoAb with different chemotherapy bases are not consistent.

Data sources: This meta-analysis includes published of the PubMed and Embase databases, limited to English literature, and patients were treated with MoAb combination. Randomized control trials conducted published up to May 2021 were considered for inclusion.

Therapeutic advances: Fluoropyrimidine-based chemotherapy has been the backbone of palliative therapy for mCRC, with demonstrated benefits. This article will review the efficacy and safety of randomized control trials comparing different MoAb with fluoropyrimidine-based chemotherapy as first-line therapy for patients with mCRC, particularly in Kirsten rat sarcoma wild-type.

Conclusion: This meta-analysis revealed that MoAb plus chemotherapy has better progression-free survival and objective response rate than chemotherapy alone. However, treatment-related serious adverse events (grade ≥ 3) should be considered, particularly severe rash, diarrhea, and hypertension.