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
In brief
Anti-EGFR drugs double response rates without extending survival in liver-only CRC
A meta-analysis of six trials in 795 patients with RAS-wild type colorectal liver metastases found that adding an EGFR inhibitor to chemotherapy roughly doubled tumor response and deepened shrinkage, yet progression-free and overall survival were unchanged and resection rates were similar. The results highlight a trade-off between tumor shrinkage and real-world outcomes, prompting further study of how to translate deeper responses into surgical cure.
- Journal
- Critical reviews in oncology/hematology (Q1)
- Published
- 6 August 2026
- Study design
- Systematic review / meta-analysis of RCTs
- Evidence level
- Level 1, High (CEBM 1a)
- Authors
- Salvatore Corallo, Ottavia Cicerone, Cecilia Brigati, Anna Pagani, Luigi Colletto, Benedetta Pellizzari, et al.
- PMID
- 42562243
- DOI
- 10.1016/j.critrevonc.2026.105515
Why clinicians should know about it
- Picked for Geriatrics and Gerontology (top studies of the week, 9 August 2026).
- Picked for Oncology and Radiation Oncology (top studies of the week, 9 August 2026): Conversion strategies EGFRi vs bevacizumab in RAS‑wt CRLM
- Picked for Hematology (top studies of the week, 9 August 2026).
Abstract
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.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.