Fruquintinib 5mg capsules

Objective: The efficacy of regorafenib or fruquintinib in combination with PD-1/PD-L1 inhibitors for metastatic colorectal cancer (mCRC) treatment has not been elucidated. This study aims to systematically evaluate the efficacy and safety of this combination therapy. Methods: PubMed, Embase, Cochrane Library, and Web of Science were systematically retrieved until July 24, 2024. A meta-analysis was carried out for the overall objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and the incidence of grade 3 or higher treatment-related adverse events (AEs). Non-overlapping 95% confidence intervals (CIs) were considered statistically significant. Results: 26 studies encompassing 1,409 patients were analyzed. Pooled analysis revealed an ORR of 6% (95% CI: 3%-12%), a DCR of 62% (95% CI: 55%-68%), a median PFS of 3.84 months (95% CI: 3.19-4.49 months), a median OS of 13.08 months (95% CI: 10.17-16.00 months), and an incidence rate of grade 3-4 AEs of 21% (95% CI: 15%-28%). In subgroup analyses, the fruquintinib-based regimen demonstrated significantly superior efficacy compared to regorafenib-based therapy, with higher ORR (16% [95% CI: 13%-21%] vs 3% [95% CI: 1%-9%]), DCR (79% [95% CI: 72%-85%] vs 54% [95% CI: 47%-61%]), and median PFS (5.40 months [95% CI: 4.60-6.19] vs 3.00 months [95% CI: 2.47-3.52]). Median OS was numerically but not significantly longer with fruquintinib (14.35 months [95% CI: 10.68-18.02] vs 12.70 months [95% CI: 8.79-16.61]). Liver metastasis status strongly influenced outcomes, with significantly lower ORR (3% [95% CI: 1%-13%] vs 49% [95% CI: 32%-76%]) and shorter median PFS (2.37 months [95% CI: 1.77-2.96] vs 3.50 months [95% CI: 3.09-3.91]) in patients with liver involvement. Conclusion: The combination of regorafenib or fruquintinib with PD-1/PD-L1 shows moderate efficacy and acceptable safety in the treatment of mCRC. The fruquintinib-based regimen may be superior to the regorafenib-based regimen, and patients without liver metastasis may derive greater benefits. These findings offer new insights for treating mCRC, although they should be validated through large randomized controlled trials. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO, identifier CRD42024582268.

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Colorectal cancer (CRC) is one of the most common malignancies worldwide, with high morbidity and mortality rates. Conventional treatments, including surgery, radiotherapy, and chemotherapy, have limited effects on advanced and metastatic CRC (mCRC). Fruquintinib, a novel and highly selective vascular endothelial growth factor receptor (VEGFR) inhibitor, has shown significant efficacy and tolerance in treating mCRC. The FRESCO and FRESCO-2 trials demonstrated that fruquintinib significantly prolongs progression-free survival and the overall survival of refractory mCRC patients, establishing it as the standard third-line treatment strategy for mCRC. In addition, the combination of fruquintinib with other anticancer drugs and immune checkpoint inhibitors demonstrated potential for enhanced efficacy, which warrants further exploration. In this review, we aimed to systematically summarize the current knowledge about the pharmacological mechanisms, pharmacokinetic characteristics, adverse events, and corresponding treatment options of fruquintinib and provide an update on the clinical trials related to fruquintinib in CRC by conducting a comprehensive literature search of PubMed and consulting the relevant clinical trials via ClinicalTrials.gov and the ChiCTR website, aiming to offer new insights into the role of fruquintinib in the comprehensive treatment of CRC.

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SMARCA4-deficient non-small cell lung cancer (SMARCA4-dNSCLC) typically lacks target-driven gene alterations and are primarily resistant to cytotoxic drugs. There is currently no standard treatment, especially for those who are unwilling or unable to receive chemotherapy. This case reported that chemotherapy-free strategy with tislelizumab and fruquintinib was utilized as a first-line treatment for a patient with SMARCA4-deficient NSCLC, and the patient achieved remarkable partial remission and lasted more than two years of disease control without severe adverse events.

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BACKGROUND: Immune checkpoint inhibitors (ICIs) in combination with antiangiogenic drugs have shown promising outcomes in the third-line and subsequent treatments of patients with microsatellite stable metastatic colorectal cancer (MSS-mCRC). Radiotherapy (RT) may enhance the antitumor effect of immunotherapy. However, the effect of RT exposure on patients receiving ICIs and targeted therapy remains unclear. This study aimed to investigate the association between RT exposure and clinical responses to fruquintinib (a highly selective tyrosine kinase inhibitor of vascular endothelial growth factor receptor) plus sintilimab (an anti-programmed death 1 antibody; F&S) in previously treated patients with MSS-mCRC and to explore predictive biomarkers. METHODS: In this prospective observational study, patients with mCRC receiving F&S as third-line or subsequent treatment were enrolled. Eligible patients were divided into the RT cohort (RTC) and the non-RT cohort (NRTC) according to their RT history. The primary endpoint was the objective response rate (ORR). Secondary endpoints included disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety. Pretreatment fecal and serum samples were collected for microbiome analysis, metabolome analysis, and immune signatures to identify biomarkers for treatment. RESULTS: , and PC(20:5(5Z,8Z,11Z,14Z,17Z)/20:3(8Z,11Z,14Z)) in RTC significantly predicted better DCR and PFS, whereas guanosine and interleukin-10 predominated in patients with NRTC were negatively correlated with PFS and OS. CONCLUSIONS: Patients with RT exposure benefited significantly from F&S in the third-line or subsequent treatment for MSS-mCRC. Gut microbiota, metabolites, and cytokines may help predict F&S outcomes for mCRC, which may be helpful in treatment decision-making. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov identifier: NCT05635149.

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Background: Fruquintinib, a selective vascular endothelial growth factor receptor (VEGFR) inhibitor, has shown considerable efficacy in colorectal cancer (CRC) treatment. Despite its promising therapeutic effects, the precise molecular mechanisms underlying its therapeutic effects remain incompletely understood. In this study, we explored the functional roles and molecular mechanisms of fruquintinib in CRC therapy. Material and methods: Human CRC cells (HCT-116 and LOVO) were cultured and treated with fruquintinib. Cell counting kit-8 assay kit (CCK-8) and colony formation assays were performed to investigate the effects of fruquintinib on cell proliferation. Wound healing and transwell assays were conducted to explore the role of fruquintinib on migration and invasion. RNA sequencing and bioinformatics analysis was used to investigate the potential mechanism of fruquintinib in the development of CRC. Western blot was used to measure the protein level. Results: Fruquintinib significantly inhibited the proliferation, migration, and invasion of colorectal cancer cells. Bioinformatics analysis indicated that fruquintinib modulated the epithelial-mesenchymal transition (EMT) pathway, and experimental validation confirmed its regulatory effects on core EMT-associated protein biomarkers. Notably, fruquintinib treatment resulted in the upregulation of E-cadherin and the downregulation of N-cadherin, vimentin, and MMP9. Western blot analysis revealed that fruquintinib dose-dependently suppressed SMAD2/3 expression. Notably, treatment with the TGF-β receptor agonist KRFK TFA attenuated fruquintinib's effect, reversing the upregulation of E-cadherin as well as the downregulatin of N-cadherin and SMAD2/3. Additionally, KRFK TFA partially restored CRC cell migration and invasion in transwell assays, counteracting fruquintinib's inhibitory impact. Conclusion: These findings indicate that Fruquintinib effectively hampers the migration and invasion of CRC cells by disrupting the EMT process via the TGF-β/Smad signaling pathway. This study sheds light on the mechanisms by which fruquintinib inhibits CRC progression and underscores its potential for further clinical investigation.

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