Conversion strategies in RAS wild-type colorectal liver metastases: a systematic review and meta-analysis of first-line trials comparing regimens with anti-epidermal growth factor receptor inhibitors versus bevacizumab.

The selection of optimal conversion therapy for patients with initially unresectable colorectal liver metastases (CRLM) remains a significant clinical challenge. In patients with RAS wild-type disease, a key therapeutic decision involves whether to combine chemotherapy with an EGFR inhibitor (EGFRi) or bevacizumab. A systematic literature review and meta-analysis of randomised controlled trials (RCTs) published between 2015 and 2025 were conducted to compare chemotherapy plus either an EGFRi or bevacizumab as first-line treatment for patients with RAS wild-type metastatic colorectal cancer and liver-limited disease. Analyses encompassed both the overall population and subgroups defined by primary tumor location (PTL). Six RCTs, including data from 795 patients with CRLM, were identified. No statistically significant differences were found between EGFRi- and bevacizumab-based regimens for progression-free survival (PFS) and overall survival (OS). Four studies contributed to analyses of response rate (RR) and complete (R0) resection rate, while three studies contributed to the depth of response (DpR) analysis. EGFRi-based regimens demonstrated statistically significant improvements in both RR and DpR, with pooled odds ratios (ORs) of 1.98 and 1.70, respectively. No statistically significant difference in R0 resection rates was observed. Subgroup analyses by PTL revealed no statistically significant survival advantage for either agent in either left- or right-sided subgroups. This comprehensive meta-analysis identified no significant survival advantage for either anti-EGFRs or bevacizumab in patients with initially unresectable RAS wild-type CRLM. Further research is warranted to elucidate why the increased and deeper responses observed with anti-EGFRs do not result in higher R0 resection rates or improved survival.