Yoshino T, Hooda N, Younan D, Shitara K, Heinemann V,… Suh M, Reichert H,… Fryzek J, et al. 2023. 127P A meta-analysis of efficacy and safety from head-to-head first-line (1L) trials of epidermal growth factor receptor inhibitors (EGFRIs) versus bevacizumab in combination with chemotherapy (CT) doublets in patients with RAS wild-type (WT) metastatic colorectal cancer (mCRC) by sidedness. Ann Oncol 34(Suppl 4):S1519 [abstract]; DOI:https://doi.org/10.1016/j.annonc.2023.10.262.
Abstract
Background
The 1L treatment choice of EGFRIs plus doublet CT vs. bevacizumab plus doublet CT remains a topic of interest for patients with left-sided RAS WT mCRC. We conducted a systematic literature review and meta-analysis of clinical trial data published between 2015 and 2023.
Methods
We evaluated the relative efficacy of 1L EGFRIs plus doublet CT (FOLFIRI or FOLFOX) vs. bevacizumab plus doublet CT on overall survival (OS), progression-free survival (PFS), objective response rate (ORR), early tumor shrinkage (ETS), resection rate (RR), and safety for patients with RAS WT left-sided mCRC. We also assessed the relative efficacy and safety in all-sided and right-sided tumors.
Results
Eight trials were included with 2624 patients. Five trials reported outcomes by tumor sidedness. In the left-sided population, OS favored EGFRI plus CT (Hazard Ratio (HR)=0.77; 95% Confidence Interval (CI): 0.68-0.87), while PFS trended towards favoring EGFRI plus CT (HR=0.93, 95% CI: 0.84-1.04). In the all-sided population, OS favored EGFRI plus CT (HR=0.85, 95% CI: 0.78-0.93), while no statistically significant difference was detected for PFS. In the right-sided population, OS trended towards favoring bevacizumab plus CT (HR=1.17, 95% CI: 0.95-1.44) as well as with PFS (HR=1.45, 95% CI: 1.19-1.78). ORR was greater in the EGFRI plus CT group in left-sided (Odds ratio [OR]=1.61, 95% CI: 1.30-1.99) and all-sided (OR=1.29, 95% CI: 1.09-1.52) tumors, but no significant difference was found for right-sided tumors (OR=0.99, 95% CI: 0.69-1.41). ETS in the all-sided population favored EGFRI plus CT (OR=1.72; 95% CI: 1.36-2.17); limited data precluded evaluation by sidedness. RR was reported in 2 studies without significant difference between treatment arms and regardless of sidedness. Safety was available in 6 trials for all-sided tumors and 1 trial for left-sided tumors, each demonstrating typical class-specific adverse events.
Conclusions
This most comprehensive meta-analysis indicates a benefit for 1L EGFRI plus CT over bevacizumab plus CT in patients with left-sided RAS WT mCRC.