Maintenance therapy with Fluoropyrimidine and cetuximab or bevacizumab after first line FOLFOX-chemotherapy in metastatic colorectal cancer according to RAS or BRAFV600E mutation status

Abstract

Fluoropyrimidine (FP) and oxaliplatin-based chemotherapy is the standard rst-line treatment for metastatic colorectal cancer (mCRC); however, oxaliplatin-induced neuropathy critically affects the quality of life of patients. Maintenance strategies with FP plus bevacizumab have been well established; nonetheless, the real-world outcomes of maintenance therapy with FP and cetuximab are unclear. We investigated the clinical outcomes of patients who underwent maintenance therapy with cetuximab. MethodsWe retrospectively identi ed and analyzed patients with mCRC who were treated between 2012 and 2021 with rst-line oxaliplatin-based induction chemotherapy (IC) and patients treated with maintenance therapy after IC. ResultsA total of 112 patients were treated with IC. Among them, 48 patients underwent maintenance therapy (same IC regimen without oxaliplatin). The most common reason for the discontinuation of IC was peripheral neuropathy (n = 40, 83%). For the IC of the maintenance group, 3, 26, and 19 patients were treated with CAPOX (capecitabine/oxaliplatin), mFOLFOX6 (FP/leucovorin/oxaliplatin) plus bevacizumab, and mFOLFOX6 plus cetuximab. The best overall response of maintenance therapy was a partial response in 7 patients and stable disease in 30 patients The median progression-free survival (PFS) of maintenance therapy and overall survival (OS) was 4.83 months and 25.6 months in the bevacizumab group, and 5.98 months and 32.4 months in the cetuximab group, respectively. ConclusionsMaintenance therapy with FP and cetuximab is a feasible strategy for appropriate mCRC patients. Further large-scale randomized studies are needed to validate the e cacy of anti-epidermal growth factor receptor-based maintenance therapy.

Role and Function of Receptor Tyrosine Kinases in BRAF Mutant Cancers

“…A pooled analysis of anti-angiogenic biologicals, including bevacizumab, ramucirumab, and aflibercept, confirmed the efficacy of these drugs as a second-line treatment of pre-treated BRAF mutant CRC [188]. In addition, a retrospective analysis of the maintenance therapy of FOLFOX-pre-treated BRAF V600E metastatic CRC with bevacizumab plus fluoropyrimidine showed high disease control (74%), and overall survival (25.6 months), warranting further large-scale trials of this promising second-line combination therapy in the future [189]. The global phase 3 RAISE trial with metastatic CRC patients pre-treated with bevacizumab, oxaliplatin, and fluoropyrimidine showed that the anti-VEGFR2 antibody ramucirumab plus FOLFIRI prolonged overall survival and progression-free survival together with an increase of side effects (neutropenia, thrombocytopenia, stomatitis, epistaxis, and hypertension) when compared with FOLFIRI plus placebo, which was accompanied by a substantial benefit of ramucirumab plus FOLFIRI in BRAF mutant patient groups [190].…”