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

• Published in: The oncologist (Dayton, Ohio) Ohio), 2021-04, Vol.26 (4), p.302-309
• Main Authors: Pietrantonio, Filippo, Fucà, Giovanni, Rossini, Daniele, Schmoll, Hans‐Joachim, Bendell, Johanna C., Morano, Federica, Antoniotti, Carlotta, Corallo, Salvatore, Borelli, Beatrice, Raimondi, Alessandra, Marmorino, Federica, Niger, Monica, Boccaccino, Alessandra, Masi, Gianluca, Lonardi, Sara, Boni, Luca, Braud, Filippo, Di Bartolomeo, Maria, Falcone, Alfredo, Cremolini, Chiara
• Format: Article
• Language: English
• Subjects: Antimitotic agents; Antineoplastic agents; Bevacizumab; Care and treatment; Chemotherapy, Combination; Colorectal cancer; Combination chemotherapy; Development and progression; Diagnosis; Dosage and administration; FOLFOX; FOLFOXIRI; Gastrointestinal Cancer; Gene mutations; Genetic aspects; Health aspects; Metastasis; Metastatic colorectal cancer; Panitumumab; Patient outcomes
• ISSN: 1083-7159; 1549-490X
• DOI: 10.1002/onco.13642

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 FOLFOXIRI‐bevacizumab is superior to doublets plus bevacizumab independently from primary tumor sidedness and RAS/BRAF status. No randomized comparison between FOLFOXIRI‐bevacizumab versus doublets plus anti‐EGFRs is available in left‐sided RAS/BRAF wild‐type mCRC. Materials and Methods We selected patients with left‐sided 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 FOLFOX‐panitumumab. 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 FOLFOXIRI‐bevacizumab 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 FOLFOXIRI‐bevacizumab 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‐type mCRC. 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 FOLFOX‐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‐bevac