Anti-EGFR plus chemotherapy vs. chemotherapy alone in RAS wild-type colorectal liver metastases: A meta-analysis of survival outcomes in resectable and unresectable settings.

[BACKGROUND] The benefit of adding anti-EGFR therapy to chemotherapy in RAS wild-type colorectal liver metastases (CRLM) is well established in unresectable patients but remains controversial in resectable ones.

[AIM] To evaluate the impact of anti-EGFR therapy combined with chemotherapy versus chemotherapy alone on survival outcomes in patients with RAS wild-type CRLM, stratified by resectability status.

[METHODS] A systematic literature search across multiple databases identified eligible clinical trials comparing anti-EGFR agents plus chemotherapy versus chemotherapy alone in RAS wild-type CRLM. Pooled hazard ratios (HRs) for recurrence-free survival (RFS) and overall survival (OS) were calculated using a random-effects model. Subgroup analyses were conducted based on resectability.

[RESULTS] In the overall analysis, anti-EGFR therapy was associated with non-significant trends toward improved RFS (HR = 0.873; 95 % CI: 0.662-1.150) and OS (HR = 0.835; 95 % CI: 0.539-1.293).In the unresectable subgroup, anti-EGFR therapy significantly improved OS (HR = 0.601; 95 % CI: 0.423-0.854).Conversely, in the resectable subgroup, no benefit was observed for RFS (HR = 1.083; 95 % CI: 0.865-1.356) or OS (HR = 1.120; 95 % CI: 0.718-1.745).

[CONCLUSION] The survival benefit of anti-EGFR therapy in RAS wild-type CRLM appears to be limited to patients with unresectable disease. In resectable settings, its use may be futile or even detrimental. These findings support a reevaluation of anti-EGFR therapy in the perioperative management of CRLM and underscore the need for predictive biomarkers to guide treatment selection.