Efficacy and Safety of Fruquintinib Plus PD-1 Inhibitors Versus Regorafenib Plus PD-1 Inhibitors in Refractory Microsatellite Stable Metastatic Colorectal Cancer

Abstract

BackgroundMicrosatellite stability (MSS) or mismatch repair proficient (pMMR) metastatic colorectal cancer (mCRC) is resistant to immune checkpoint inhibitors. Studies have shown that antiangiogenic drugs combined with programmed death receptor-1 (PD-1) inhibitors can improve immunosuppression. The purpose of this study was to compare the efficacy of fruquintinib combined with PD-1 inhibitor (FP) and regorafenib combined with PD-1 inhibitor (RP) in the treatment of advanced mCRC with MSS or pMMR.Materials and MethodsWe retrospectively collected advanced MSS or pMMR mCRC patient data from The Second Affiliated Hospital of Nanchang, China, from June 2019 to March 2021. Then, we analyzed and compared the efficacy and safety of FP and RP.ResultsA total of 51 patients who met the criteria were divided into FP (n = 28) and RP groups (n = 23). The overall response rate of the FP and RP groups was 7.1% and 8.7% and the disease control rate was 89.3% and 56.5%, respectively. The median progression-free survival (PFS) time was higher in the FP group than in the RP group (6.4 vs. 3.9 months, respectively; P = 0.0209). Patients with no liver metastasis, KRAS wild type, and left colon tumor may benefit from FP. Eight patients (15.7%) had grade 3 toxicity related to treatment. Cox multivariate regression analysis showed that the treatment method was an independent risk factor for median PFS time.ConclusionOur study indicates that FP could improve PFS time of patients with advanced mCRC compared with RP.

Metastatic sites and lesion numbers cooperated to predict efficacy of PD‐1 inhibitor‐based combination therapy for patients with metastatic colorectal cancer

“…Thus, a large cohort was warranted to further evaluate the role of RAS mutation in mCRC. Besides, with limited studies assessing the efficacy of fruquintinib‐combined therapy, a retrospective study indicated that fruquintinib prolonged the survival of patients with MSS mCRC than regorafenib though only 51 patients were included in this study (fruquintinb cohort, n = 28; regorafenib cohort, n = 23) 16 . However, no significant difference was observed in our study (fruquintinb cohort, n = 29; regorafenib cohort, n = 51).…”

Biomarkers and factors in small cell lung cancer patients treated with immune checkpoint inhibitors: A meta‐analysis

“…Among them, the microenvironment of the liver may be more suitable for the survival of SCLC cells with neuroendocrine characteristics, which may be related to the high propensity of SCLC to develop liver metastasis 82 . The liver is an immunosuppressed organ when liver metastases occur, therefore the efficacy of ICIs can be diminished by a decrease in immune response in both liver metastases and primary hepatocellular carcinoma 83,84 . Tumeh et al 85 observed a significant reduction in the density of CD8 + T cells at the margins of liver metastatic tumors in melanoma patients, which is one of the reasons for the decreased immune response.…”

Synergistic antitumor activity of regorafenib and rosuvastatin in colorectal cancer

“…( Wilhelm et al, 2011 ) Regorafenib is mainly transformed into active metabolites M-2 and M-5, thus inhibiting multiple kinases, including VEGFR 1–3, KIT, PDGFR-alpha/beta, FGFR1/2, RET, etc. ( Ettrich and Seufferlein, 2018 ) Up to now, regorafenib has been widely utilized to treatment colorectal cancer, especially metastatic colorectal cancer ( Van Cutsem et al, 2019 ; Sun et al, 2021 ). An international clinical trial was performed to test the efficacy of regorafenib in patients with metastatic colorectal cancer progressing after all approved standard therapies and found the median overall survival was 6.4 months in the regorafenib group while that of placebo group was 5.0 months ( Grothey et al, 2013 ).…”