Yoshino T, Hooda N, Younan D, Shitara K, Heinemann V,…, Suh M, Reichert H, et al. 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. Abstract 127P, European Society for Medical Oncology (ESMO) Asia Congress. Ann Oncol 34(Sup 4):S1519; doi: 10.1016/j.annonc.2023.10.262. Singapore, December 2023.
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.