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

Abstract

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‐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.

First-line systemic treatment strategies in patients with initially unresectable colorectal cancer liver metastases (CAIRO5): an open-label, multicentre, randomised, controlled, phase 3 study from the Dutch Colorectal Cancer Group

“…A limitation of this study might be that the use of FOLFOXIRI was not investigated in patients with a left-sided and RAS and BRAF V600E wild-type tumour. However, in this population a propensity score-based analysis showed no benefit of FOLFOXIRI plus bevacizumab compared with FOLFOX plus panitumumab, 30 and a phase 3 study showed no benefit of FOLFOXIRI plus panitumumab compared with FOLFOX plus panitumumab. 31 Our results show that FOLFOXIRI plus bevacizumab should be preferred as a systemic induction regimen for patients with initially unresectable colorectal cancer liver metastases and a right-side or RAS or BRAF V600E mutated tumour, or both.…”

Initial Panitumumab Plus Fluorouracil, Leucovorin, and Oxaliplatin or Plus Fluorouracil and Leucovorin in Elderly Patients With RAS and BRAF Wild-Type Metastatic Colorectal Cancer: The PANDA Trial by the GONO Foundation

“…Small studies with low level of evidence underscored the feasibility and satisfactory outcomes of initial anti-EGFR-based therapy in older patients with mCRC. [26][27][28][29][30] Nevertheless, anti-EGFR monotherapy is recommended in patients judged unfit for chemotherapy including fluoropyrimidine monotherapy. 16,31 The PANDA study is a unique trial specifically conducted in elderly patients fit enough to potentially receive first-line therapy with an anti-EGFR agent added to a chemotherapy backbone including a modified schedule of FOLFOX.…”

Colorectal signet‐ring cell carcinoma treated with FOLFOX plus panitumumab

“…However, the effectiveness of panitumumab for colorectal SRCC in children has not yet been clarified. According to studies on FOLFOX plus panitumumab chemotherapy for wild‐type RAS metastatic CRC in adult patients, the response rate was 52%–77%, and the rate of second resection was 9%–18% 4 …”

“…According to studies on FOLFOX plus panitumumab chemotherapy for wild-type RAS metastatic CRC in adult patients, the response rate was 52%-77%, and the rate of second resection was 9%-18%. 4 The patient reported here experienced Common Terminology Criteria for Adverse Events grade IV neutropenia and grade III oral mucositis during chemotherapy at 2-or 3-week intervals. However, the patient had no intractable complications including chronic oxaliplatininduced neuropathy that could result in dose reduction or alter the chemotherapy after the implementation of treatment at 4 week intervals, and this could also have contributed to the good outcome in this patient.…”