A meta-analysis of efficacy and safety data from head-to-head first-line trials of epidermal growth factor receptor inhibitors versus bevacizumab in adult patients with RAS wild-type metastatic colorectal cancer by sidedness

• Published in: European journal of cancer (1990) 2024-05, Vol.202, p.113975-113975, Article 113975
• Main Authors: Yoshino, Takayuki, Hooda, Naushin, Younan, Diana, Muro, Kei, Shitara, Kohei, Heinemann, Volker, O’neil, Bert Howard, Herrero, Fernando Rivera, Peeters, Marc, Soeda, Junpei, Suh, Mina, Reichert, Heidi, Mezzi, Khalid, Fryzek, Jon, Chia, Victoria, Rehn, Marko, Stintzing, Sebastian
• Format: Article
• Language: English
• Subjects: Adult; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Bevacizumab; Bevacizumab - adverse effects; Cetuximab; Cetuximab - adverse effects; Colonic Neoplasms - drug therapy; Colorectal Neoplasms - drug therapy; Colorectal Neoplasms - genetics; EGFR; ErbB Receptors; Fluorouracil - therapeutic use; Humans; Left-sided; Meta-analysis; Metastatic colorectal cancer; Panitumumab; Progression-free survival; RAS wild-type; Rectal Neoplasms - drug therapy; Survival; Systematic literature review; VEGF
• ISSN: 0959-8049; 1879-0852
• DOI: 10.1016/j.ejca.2024.113975

The first-line treatment choice of EGFRIs plus doublet chemotherapy vs. bevacizumab plus doublet chemotherapy 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 2024. We evaluated the relative efficacy and safety of first-line EGFRIs plus doublet chemotherapy (FOLFIRI or FOLFOX) vs. bevacizumab plus doublet chemotherapy for patients with RAS WT left-sided mCRC, as well as in all- and right-sided tumors. We identified eight trials with 2624 patients. Five trials reported outcomes by tumor sidedness. In the left-sided population, overall survival (OS) (Hazard Ratio (HR) = 0.80, 95% Confidence Interval (CI): 0.71–0.90) and objective response rate (ORR) (Odds ratio [OR]=1.61, 95% CI: 1.30–1.99) favored EGFRI plus chemotherapy, while no statistically significant differences were observed for progression-free survival (PFS) (HR=0.93, 95% CI: 0.84–1.04) or resection rate (RR). Similar results were found in the all-sided population. In the right-sided population, PFS favored bevacizumab plus chemotherapy (HR=1.45, 95% CI: 1.19–1.78), while no statistically significant differences were observed for OS (HR=1.17, 95% CI: 0.95–1.44), ORR (OR=0.99, 95% CI: 0.69–1.41), and RR. Early tumor shrinkage in the all-sided population favored EGFRI plus chemotherapy (OR=1.72; 95% CI: 1.36–2.17); limited data precluded evaluation by 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. This most comprehensive meta-analysis indicates a benefit for first-line EGFRI plus chemotherapy over bevacizumab plus chemotherapy in patients with left-sided RAS WT mCRC. •Meta-analysis of 8 first-line trials comparing EGFRIs to bevacizumab in RAS WT mCRC.•In patients with left- and all-sided tumors, EGFRI improved OS and ORR vs bevacizumab.•Bevacizumab improved PFS in patients with right-sided tumors.•EGFRI improved ETS in patients with all-sided tumors.•Typical class-specific AEs observed in both treatment arms.