Comparison of the efficacy and safety of fruquintinib and regorafenib in the treatment of metastatic colorectal cancer: A real-world study

Abstract

BackgroundFruquintinib and regorafenib have been approved for the third-line therapy of metastatic colorectal cancer (mCRC) in China. However, at present, there is a lack of head-to-head clinical trials on the comparison of efficacy and safety between the two drugs.Materials and methodsThe data of patients with mCRC who were treated with fruquintinib or regorafenib after the standard chemotherapy in Zhejiang Provincial People’s Hospital from October 2018 to November 2021 were collected and analyzed. The primary endpoints were overall survival (OS), progression-free survival (PFS) and adverse events. The secondary endpoints were the appropriate sequence, objective remission rate (ORR) and disease control rate (DCR) of fruquintinib and regorafenib.ResultsA total of 105 patients were enrolled in this study. The ORR of fruquintinib group (n=55) and regorafenib group (n=50) were 6.1% and 2.0%; the DCR were 65.3% and 54.2%, respectively. There was no significant difference in median OS (mOS) and PFS (mPFS) between the two groups (mOS:14.2 vs12.0 months, p=0.057; mPFS:4.4 vs 3.5 months, p=0.150). Combined immunotherapy showed a synergistic effect. The mPFS and mOS of fruquintinib combined with anti-PD-1 therapy were longer than those of fruquintinib monotherapy (mPFS:5.9 vs 3.0 months, p=0.009; mOS:17.5 vs 11.3 months, p=0.008). The mOS of patients treated with regorafenib combined with anti-PD-1 therapy was 14.8 months higher than that of regorafenib monotherapy (p=0.045). When combined with anti-PD-1 therapy, the mPFS and mOS of fruquintinib was significantly longer than regorafenib (mPFS:5.9 vs 3.8 months, p=0.018; mOS:17.5 vs 14.8 months, p=0.044). In the treatment sequence, the OS of patients treated with regorafenib and then fruquintinib was significantly longer than that of the reverse treatment sequence (15.0 vs 8.3 months, p=0.019). The adverse reactions were generally similar, but the incidence of hand-foot syndrome of regorafenib was higher than that of fruquintinib, while fruquintinib was more prone to grade 3 hypertension.ConclusionFruquintinib monotherapy showed better disease control rate and objective remission rate in the post-line therapy of metastasis colorectal cancer. Notably, the combination of PD-1 immunotherapy brought the additional effect, especially in the fruquintinib combined with anti-PD-1 therapy. Patients treated with regorafenib and then fruquintinib was significantly longer than that of the reverse treatment sequence. The toxicity of fruquintinib and regorafenib are similar.

Efficacy comparison of fruquintinib, regorafenib monotherapy or plus programmed death-1 inhibitors for microsatellite stable metastatic colorectal cancer

“…The results of Deng et al [ 31 ] suggested that FP had a better PFS (5.9 vs 3.0 months, P = 0.009) and OS (17.5 vs 11.3 months, P = 0.008) than F in the treatment of mCRC. FP also had a longer PFS (5.9 vs 3.8 months, P = 0.018) and OS (17.5 vs 14.8 months, P = 0.044) than RP.…”

“…Notably, Deng et al [ 31 ] found that although there was no significant difference in median PFS between RP and R (3.8 vs 2.4 months, P = 0.262), RP had a longer OS than R (14.8 vs 10.0 months, P = 0.045), which was inconsistent with our findings [median OS (RP: 14.1 months, R: 15.7 months, P = 0.08)]. In a real-world study, Jiang et al [ 32 ] also reported that RP did not prolong the median OS compared with R alone (11.0 vs 11.2 months, P = 0.814).…”

Feasibility and Tolerability of Anlotinib Plus PD-1 Blockades for Patients with Treatment-Refractory Metastatic Colorectal Cancer: A Retrospective Exploratory Study

“… 7 However, many patients might progress of the first-line therapy and switch to other combined chemotherapy regimens as second-line treatment, achieving survival benefits consecutively. 8 Still and all, a certain amount of patients were able to receive the third-line treatment; to our knowledge, the FRESCO and CONCUR trials convinced that the antiangiogenic small-molecule tyrosine kinase blockades (TKIs) fruquintinib and regorafenib might further bring survival benefits for patients with CRC and were approved by guidelines as the third-line treatment for patients with metastatic CRC in China, respectively. 9 , 10 However, the disappointing ORR of fruquintinib and regorafenib (4.7% and 4.0%, respectively) highlighted that novel therapeutic options were still needed to be explored to provide patients with promising efficacy and acceptable safety profile in clinical practice.…”

Exploring non-toxic co-evolutionary docking

“…The Vascular Endothelial Growth Factor 2 is a receptor of tyrosine kinases that have been implicated in tumor angiogenesis, a key feature of many cancers 48 . However, the number of drugs for cancer treatments targeting Vegfr2 are limited 49 . Sorafenib is the main reference ligand as an oral multi-target kinase inhibitor of tumor genesis and angiogenesis.…”