FOLFOXIRI-Bevacizumab or FOLFOX-Panitumumab in Patients with Left-Sided RAS / BRAF Wild-Type Metastatic Colorectal Cancer: A Propensity Score-Based Analysis

Background. Doublets plus anti-epidermal growth factor receptors (EGFRs) are the preferred upfront option for patients with left-sided RAS/BRAF wild-type metastatic colorectal cancer (mCRC). Initial therapy with FOLFOXIRIbevacizumab is superior to doublets plus bevacizumab independently from primary tumor sidedness and RAS/BRAF status. No randomized comparison between FOLFOXIRIbevacizumab versus doublets plus anti-EGFRs is available in left-sided RAS/BRAF wild-type mCRC. Materials and Methods. We selected patients with leftsided RAS and BRAF wild-type mCRC treated with first-line FOLFOX-panitumumab or FOLFOXIRI-bevacizumab in five randomized trials: Valentino, TRIBE, TRIBE2, STEAM, and CHARTA. A propensity score-based analysis was performed to compare FOLFOXIRI-bevacizumab with FOLFOXpanitumumab. Results. A total of 185 patients received FOLFOX-panitumumab and 132 received FOLFOXIRI-bevacizumab. Median progression-free survival (PFS) and median overall survival (OS) were 13.3 and 33.1 months in the FOLFOXIRIbevacizumab group compared with 11.4 and 30.3 months in the FOLFOX-panitumumab group (propensity score-adjusted hazard ratio (HR) for PFS, 0.82; 95% confidence interval (CI), 0.64–1.04; p = . 11; propensity score-adjusted HR for OS, 0.80; 95% CI, 0.59–1.08; p = . 14). No significant differences in overall response rate and disease control rate were observed. A statistically nonsignificant difference in favor of FOLFOXIRIbevacizumab was observed for OS after secondary resection of metastases. Chemotherapy-related adverse events were more frequent in the FOLFOXIRI-bevacizumab group, with specific regard to grade 3 and 4 neutropenia (48% vs. 26%, adjusted p = .001). Conclusion. Although randomized comparison is lacking, both FOLFOXIRI-bevacizumab and FOLFOX-panitumumab are valuable treatment options in left-sided RAS/BRAF wild-typemCRC. The Oncologist 2021;26:302–309 Implications for Practice: A propensity score-based analysis of five trials was performed to compare FOLFOX-panitumumab versus FOLFOXIRI-bevacizumab in left-sided RAS/BRAF wild-type metastatic colorectal cancer (mCRC). No significant differences were observed, but FOLFOXIRI-bevacizumab achieved numerically superior survival outcomes versus FOLFOXCorrespondence: Chiara Cremolini, M.D., Ph.D., Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa and Unit of Medical Oncology 2, Azienda Ospedaliero-Universitaria Pisana, Pisa, Via Roma 67, 56126, Pisa, Italy. Telephone: +39-050-993064; e-mail: chiaracremolini@gmail.com Received August 11, 2020; accepted for publication November 25, 2020; published Online First on January 2, 2021. http://dx.doi. org/10.1002/onco.13642 No part of this article may be reproduced, stored, or transmitted in any form or for any means without the prior permission in writing from the copyright holder. For information on purchasing reprints contact commercialreprints@wiley.com. For permission information contact permissions@wiley.com. © 2020 AlphaMed Press The Oncologist 2021;26:302–309 www.TheOncologist. com Gastrointestinal Cancer panitumumab. Chemotherapy-related adverse events were more frequent in the FOLFOXIRI-bevacizumab group. These observations suggest that although doublet chemotherapy plus anti-EGFRs remains the preferred treatment in patients with left-sided RAS/BRAF wild-type mCRC, FOLFOXIRI-bevacizumab is a valuable option able to provide similar, if not better, outcomes at the price of a moderate increase in toxicity and may be adopted based on patients’ preference and potential impact on quality of life.