Doublets plus anti‐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.
Patients 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.
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 HR for PFS, 0.82; 95% CI, 0.64‐1.04; P = 0.11; propensity score‐adjusted HR for OS, 0.80; 95% CI, 0.59‐1.08; P = 0.14). No significant differences in overall response rate and disease control rate were observed. A statistically non‐significant 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 = 0.001).
Though 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
We performed a propensity score‐based analysis of 5 trials to compare FOLFOX‐panitumumab vs FOLFOXIRI‐bevacizumab in left‐sided RAS/BRAF wild‐type mCRC. No significant differences were observed, but FOLFOXIRI‐bevacizumab achieved numerically superior survival outcomes vs FOLFOX‐panitumumab. Chemotherapy‐related adverse events were more frequent in FOLFOXIRI‐bevacizumab group. Our observations suggest that, while 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.