Conference Abstracts - 5th Binaytara Precision Oncology Summit: Redefining Cancer Treatment with Molecular Targeted Strategies
Vol. 5, Issue Supplement 1, 2025 · S1-2
Rechallenge With an Epidermal Growth Factor Receptor Inhibitor in Metastatic Colorectal Cancer: A Systematic Review and Meta-analysis
Amy Huang, MD,Gin Yi Lee, MD,Chuan Angel Lu, MD, MPH,Ibrahim Halil Sahin, MD,Gentry T. King, MD,Rachael A. Safyan, MD,Stacey A. Cohen, MD,David B. Zhen, MD,Veena Shankaran, MD,William P. Harris, MD,Andrew L. Coveler, MD,Jyoti Malhotra, MD, MPH,Victoria E. Forbes, MD, MS,Philip J. Gold, MD,E. Gabriela Chiorean, MD,Ronan W. Hsieh, MD, MS
Submission received: 2025-06-24 / Accepted: 2025-09-03 / Published: 2025-09-26
Abstract
Purpose
Clonal evolution is a mechanism of treatment resistance against epidermal growth factor receptor inhibitors (EGFRi) in metastatic colorectal cancer (mCRC). When EGFRi is discontinued, EGFRi-resistant tumor subclones decay with time, allowing for EGFRi rechallenge at a later time. We conducted a meta-analysis to investigate the efficacy of EGFRi rechallenge in mCRC.
Methods
Clinical trials and observational studies investigating the efficacy of EGFRi rechallenge in mCRC were included from PubMed and Embase from inception to December 8, 2024. Hazard ratios (HR) of overall survival (OS) and progression-free survival (PFS) were aggregated using Bayesian random-effects models. Objective response rates (ORR) were aggregated using meta-random-effects models.
Results
Twenty-nine studies were included. The pooled median PFS, median OS, and ORR were 3.83 months (95% CI, 3.25-4.50), 10.43 months (95% CI, 8.14-13.36), and 14.61% (95% CI, 8.70%-23.51%), respectively. EGFRi rechallenge was associated with significantly longer pooled PFS (HR 0.54; 95% CI, 0.31-0.93) and numerically longer pooled OS (HR 0.71; 95% CI, 0.46-1.09) than non-EGFRi systemic therapy. Patients without detectable RAS/RAF mutations by circulating tumor DNA (ctDNA) at the time of EGFRi rechallenge had significantly longer OS (HR, 0.43; 95% CI, 0.24-0.75) and PFS (HR, 0.40; 95% CI, 0.26-0.62) than those with ctDNA RAS/RAF mutations. Studies with EGFRi-free intervals ≥ 4 months prior to rechallenge (18.77%) had a numerically greater pooled ORR than those < 4 months (6.60%). No unexpected adverse events were reported, and treatment discontinuation due to adverse events was 2.7%.
Conclusion
EGFRi rechallenge is associated with significantly longer PFS, numerically longer OS, and clinically meaningful ORR as compared with non-EGFRi systemic therapy in mCRC, particularly for ctDNA RAS/RAF-wild type mCRC.