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

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.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Amgen, Inc.

Funding

Amgen, Inc.

Disclosure

T. Yoshino: Financial Interests, Personal, Invited Speaker: Chugai Pharmaceutical Co., Ltd., Merck Biopharma Co., Ltd., Bayer Yakuhin, Ltd., Ono Pharmaceutical Co., Ltd., MSD K.K., Takeda Pharmaceutical Co., Ltd.; Financial Interests, Personal, Other, Consultancy: Sumitomo Corp.; Financial Interests, Institutional, Research Grant: Ono Pharmaceutical Co., Ltd, Sanofi K.K., MSD K.K., Taiho Pharmaceutical Co., Ltd., Molecular Health GmbH, Amgen K.K., Pfizer Japan Inc., Genomedia Inc., Sysmex Corp., Daiichi Sankyo Co., Ltd., Chugai Pharmaceutical Co., Ltd., Nippon Boehringer Ingelheim Co., Ltd., Eisai Co., Ltd., Roche Diagnostics K.K., FALCO Biosystems Ltd. N. Hooda: Financial Interests, Personal, Full or part-time Employment: EpidStrategies. D. Younan: Financial Interests, Personal, Full or part-time Employment: Amgen Inc.; Financial Interests, Personal, Stocks/Shares: Amgen Inc. K. Muro: Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca, Ono, Chugai; Financial Interests, Personal, Invited Speaker: Eli Lilly, Ono, Daiichi Sankyo, Taiho, Bristol Myers Squibb, Takeda; Financial Interests, Institutional, Research Grant, Including local PI as role: Astellas, Amgen, Sanofi, Daiichi Sankyo, Taiho, MSD, Pfizer, Merck Biopharma, Eisai, Ono, Novartis; Financial Interests, Personal, Steering Committee Member: Chugai, AstraZeneca, Amgen; Non-Financial Interests, Personal, Principal Investigator: Takeda. K. Shitara: Financial Interests, Personal, Advisory Board: Lilly, Bristol Myers Squibb, Takeda, Pfizer, Ono Pharmaceutical, MSD, Taiho Pharmaceutical, Novartis, AbbVie, GSK, Daiichi Sankyo, Amgen, Boehringer Ingelheim, Guardant Health Japan Corp, Astellas Pharma Inc.; Financial Interests, Personal, Invited Speaker: Janssen Pharmaceutical K.K.; Financial Interests, Institutional, Research Grant: Astellas, Ono Pharmaceutical, Daiichi Sankyo, Taiho Pharmaceutical, Chugai Pharmaceutical, MSD, Eisai, Amgen. V. Heinemann: Financial Interests, Personal, Full or part-time Employment: LMU Klinikum der Universität München; Financial Interests, Personal, Advisory Role: Merck, Amgen, Roche, MSD, MSD Oncology, Bistrol Myers Squibbb, Novartis, Pierre Fabre, TERUMO, GSK, Servier/Pfizer, AstraZeneca; Financial Interests, Personal, Advisory Board: OncoSil, Nordic Bioscience; Financial Interests, Personal, Funding: Merck, Amgen, Roche; Financial Interests, Personal, Financially compensated role: Roche, Amgen, Sanofi, Merck, Servier, Pfizer, Pierre Fabre, AstraZeneca, MSD, Seagen. B. O’Neil: Financial Interests, Personal, Invited Speaker: AstraZeneca. F. Rivera Herrero: Financial Interests, Personal, Full or part-time Employment: Hospital Universitario Marques de Valdecilla, IDIVAL; Financial Interests, Personal, Financially compensated role: Roche, MSD, BMS, Roche, Lilly, Servier, Sanofi, AztraZeneca; Financial Interests, Personal, Funding: Roche, MSD, Merck, Amgen, BMS, Servier, Lilly; Financial Interests, Personal, Non-financial benefits: Sanofi-Aventis. J. Soeda: Financial Interests, Personal, Full or part-time Employment: Takeda Pharmaceuticals. M. Suh, H. Reichart, J. Fryzek: Financial Interests, Personal, Full or part-time Employment: EpidStrategies. K. Mezzi, V. Chia, M. Rehn: Financial Interests, Personal, Full or part-time Employment: Amgen Inc.; Financial Interests, Personal, Stocks/Shares: Amgen Inc. S. Stintzing: Financial Interests, Personal, Advisory Board: Amgen, Bayer, Lilly, Pierre Fabre, Merck KgaA, MSD, Roche, Sanofi, Taiho, Takeda; Financial Interests, Personal, Invited Speaker: Leo Pharma, AstraZeneca; Financial Interests, Institutional, Research Grant: Merck KGaA, Pierre Fabre, Roche. All other authors have declared no conflicts of interest.