Efficacy and safety of low-dose apatinib plus S-1 versus regorafenib and fruquintinib for refractory metastatic colorectal cancer: a retrospective cohort study

Abstract

Background: At present, regorafenib and fruquintinib are the standard regimens for refractory metastatic colorectal cancer patients in China, but both options have limited efficacy. The aim of this study was to investigate the efficacy and safety of low-dose apatinib plus S-1 compared with regorafenib and fruquintinib in patients with metastatic colorectal cancer (mCRC) refractory to standard therapies. Methods:The records of 114 patients with refractory mCRC in our center from April 2016 to September 2020 were retrospectively reviewed. Among these patients, 43 received apatinib 250 mg/day combined with S-1, 36 received regorafenib starting at 80 mg/day with weekly escalation, and 35 received fruquintinib 5 mg/day orally. Patients received radiographic examination every 1.5-2 months during the treatment period, progression-free survival time and overall survival time were analyzed and recorded. Results:The baseline clinical characteristics of the patients were broadly similar among the three groups.The median progression-free survival (mPFS) was 3.9 months [95% confidence interval (CI): 2.5-5.3] in the apatinib plus S-1 group, 3.1 months (95% CI: 1.9-4.2) in the fruquintinib group, and 2.4 months (95% CI: 2.1-2.7) in the regorafenib group, the mPFS of apatinib plus S-1 was significantly longer than that of regorafenib (HR =0.49, P=0.003) and fruquintinib (HR =0.60, P=0.048). The median overall survival (OS) was 8.2 months (95% CI: 5.4-11.0) in the apatinib plus S-1 group, 7.8 months (95% CI: 5.3-10.3) in the fruquintinib group, and 7.5 months (95% CI: 4.2-10.7) in the regorafenib group, which was comparable among the 3 groups. There was no statistical difference in disease control rate (DCR) among the three groups. Patients in the apatinib plus S-1 group had a higher incidence of hematological toxicity including anemia (62.8%), neutropenia (30.2%), and thrombocytopenia (39.5%), and the hand-foot skin reaction (58.3%) was more prevalent in the regorafenib group, while the adverse reaction of hypertension (45.7%) in the fruquintinib group was very significant.Conclusions: Low-dose apatinib plus S-1 prolonged PFS compared with regorafenib and fruquintinib, and is a potential alternative regimen for the treatment of refractory mCRC with tolerable and controlled toxicity.

Efficacy and Safety of Apatinib in the Treatment of Chemotherapy-Refractory Metastatic Colorectal Cancer: A Systematic Review

“…The safety profile of third-line or further-line mCRC treatments can aid clinicians in making therapy decisions and help prevent and treat possible AEs to improve quality of life [34]. AEs were graded using the common terminology criteria for adverse events (CTCAE) [9,11,[16][17][31][32][35][36][37].…”

“…The study by Dai et al was a retrospective cohort to evaluate the effectiveness and safety of apatinib and S-1 versus regorafenib versus fruquintinib in chemotherapy-refractory mCRC patients [ 11 ]. The study included 114 patients (apatinib and S-1 group = 43, regorafenib group = 36, and fruquintinib group = 35) [ 11 ].…”

“…The study by Dai et al was a retrospective cohort to evaluate the effectiveness and safety of apatinib and S-1 versus regorafenib versus fruquintinib in chemotherapy-refractory mCRC patients [ 11 ]. The study included 114 patients (apatinib and S-1 group = 43, regorafenib group = 36, and fruquintinib group = 35) [ 11 ]. PFS (median PFS was 3.9 months vs. 2.4 months vs. 3.1 months) was significantly improved in the apatinib and S-1 group versus regorafenib group versus fruquintinib group, respectively [ 11 ].…”

“…The study included 114 patients (apatinib and S-1 group = 43, regorafenib group = 36, and fruquintinib group = 35) [ 11 ]. PFS (median PFS was 3.9 months vs. 2.4 months vs. 3.1 months) was significantly improved in the apatinib and S-1 group versus regorafenib group versus fruquintinib group, respectively [ 11 ]. Median OS (8.2 months vs. 7.5 months vs. 7.8 months) was slightly increased, but no statistical difference was seen in the apatinib and S-1 group versus regorafenib group versus fruquintinib group [ 11 ].…”

“…The National Comprehensive Cancer Network (NCCN) guidelines recommend regorafenib or TAS-102 (combination of trifluridine and tipiracil hydrochloride) for third-line treatment of mCRC [10]. In China, fruquintinib is also approved in addition to the drugs mentioned above for third-line treatment [11]. Regorafenib, fruquintinib, and TAS-102 have superior efficacy compared with placebo, making them appropriate for third-line therapy, but their survival effect in phase III trials is modest [12][13][14][15].…”