Fruquintinib 5mg capsules

Abstract Background Fruquintinib is a highly selective tyrosine kinase inhibitor that targets vascular endothelial growth factor receptors (VEGFR) 1, 2, and 3, which play a critical role in angiogenesis and tumor growth. As a novel anti-angiogenic agent, Fruquintinib has demonstrated promising efficacy in the treatment of various advanced malignancies, including metastatic colorectal cancer. However, concerns about its cardiovascular safety have emerged, given that VEGFR inhibition is often associated with cardiovascular adverse events. Methodology We conducted a systematic search through PubMed, Scopus, Embase, and Web of Science to identify randomized controlled trials and cohort studies that assessed the safety of Fruquintinib compared with placebo in patients with metastatic colorectal and other cancers. The evaluated outcomes included hypertension, coronary artery disease, cerebrovascular accidents, peripheral artery disease, heart failure, thromboembolism, arrhythmias, aortic dissection, and superior vena cava syndrome. Two independent reviewers screened the titles/abstracts based on predefined inclusion and exclusion criteria, followed by a full-text review of potentially relevant studies. Any disagreements between the reviewers were resolved through consultation with a third reviewer to ensure the accuracy and consistency of the study selection. Results Fifteen reports were included in our study. Out of 3832 patients taking Fruquintinib monotherapy, a total of 997 developed hypertension with a pooled estimate incidence of 0.329 (95% CI: 0.248, 0.410; P < 0.001). In comparison to placebo, Fruquintinib was associated with significantly higher odds of developing hypertension (OR: 6.856; 95% CI: 5.071, 9.268; P < 0.001). Compared to Regorafenib, Fruquintinib demonstrated an OR of 1.549 (95% CI: 0.804, 2.983; P = 0.191) for the development of hypertension. Additionally, patients taking Fruquintinib had a pooled estimate incidence of 0.041 (95% CI: 0.021, 0.060, P < 0.001) for thromboembolism development with an OR of 2.092 (95% CI: 0.813, 5.385; P = 0.126) compared to placebo. Other reported cardiovascular side effects included sinus tachycardia, superior vena cava syndrome, peripheral edema, heart failure, myocardial enzymes elevation, and vascular access complications. Conclusion Our study found that Fruquintinib is associated with significant cardiovascular risks, with hypertension being the most common adverse event, while thromboembolism did not reach statistical significance. Therefore, close monitoring for treatment-related cardiovascular events should be considered in these patients.

Abstract licence: CC BY-NC-ND 4.0

ObjectivesTo evaluate fruquintinib’s efficacy and safety in the treatment of colorectal cancer.MethodsStudies assessing fruquintinib for colorectal cancer were included. Outcomes were overall survival (OS) and progression-free survival (PFS), and adverse reactions. A random-effects model was employed, and sensitivity analysis assessed the stability of the results and potential heterogeneity. Review Manager 5.4 and STATA 15.0 were used for analysis.ResultsEleven studies with 2,367 patients were included. Fruquintinib significantly improved OS (HR: 0.69; 95% CI: 0.58, 0.81; P < 0.00001) and PFS (HR: 0.44; 95% CI: 0.30, 0.64; P < 0.0001). No significant increase in adverse events, serious adverse events, fatigue, or hypertension. However, sensitivity analysis suggested that the risk of hypertension might be unstable, requiring further validation.ConclusionFruquintinib improves OS and PFS in colorectal cancer patients without elevating the risk of overall or serious adverse events; however, its potential impact on hypertension risk requires further investigation. Due to limitations such as small sample size, missing data, and regional bias, larger, multicenter, double-blind RCTs are needed to validate these findings.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/, CRD420251002004.

Abstract licence: CC BY 4.0

Objectives: To evaluate and indirectly compare overall survival (OS) and safety of regorafenib, fruquintinib, and trifluridine/tipiracil (TAS-102) monotherapy in refractory metastatic colorectal cancer (mCRC) beyond the third line. Methods: A systematic review and meta-analysis of phase II/III randomized controlled trials was conducted according to PRISMA guidelines. PubMed/MEDLINE, Embase, and Cochrane CENTRAL were searched from inception. Eligible studies included patients with mCRC previously treated with standard chemotherapy and biologic agents, receiving regorafenib, fruquintinib, or TAS-102 as monotherapy in the fourth line or later. OS data were reconstructed from published Kaplan-Meier curves. Pooled median and mean OS were estimated using a random-effects model, and heterogeneity was assessed using the I2 statistic. Safety outcomes were descriptively summarized. Results: Four RCTs were included. The pooled median OS was 7.83 months (95% CI: 6.98-8.80), and the pooled mean OS was 8.90 months (95% CI: 8.00-9.81), with no heterogeneity (I2 = 0%). Survival gains versus placebo ranged from 1.4 to 2.6 months. Survival curves largely overlapped, with differences below one month. Safety was consistent with known profiles. Conclusions: These agents provide comparable efficacy with modest survival benefit in late-line mCRC, highlighting the need for improved strategies and better treatment sequencing.

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IntroductionThis study aims to conduct a systematic review of cost-effectiveness studies evaluating later-line treatments for refractory metastatic colorectal cancer.MethodsThis study conducted a literature search using PubMed, Cochrane, and Embase databases. Search terms included keywords related to colorectal cancer, regorafenib, trifluridine-tipiracil, fruquintinib, and cost-effectiveness analysis. Extracted data encompassed cost-effectiveness outcomes, methodological characteristics, and the seven parameters exerting the greatest influence on incremental cost-effectiveness ratio (ICER) results.ResultsAmong 183 studies screened, a total of 11 studies met the inclusion criteria. Most studies concluded that later-line treatments for refractory metastatic colorectal cancer were not cost-effective compared to best supportive care (BSC). However, trifluridine-tipiracil was found to be cost-effective compared to BSC in some studies, and several studies reported it as a dominant option over regorafenib. Nonetheless, the cost-effectiveness outcomes between trifluridine-tipiracil and regorafenib were inconsistent across studies. Overall, drug costs and health utility values in the progressed disease state were identified as having the greatest impact on ICER outcomes.ConclusionLater-line treatments were generally not found to be cost-effective compared to BSC, mainly due to high drug costs. No treatment showed consistently favorable results across studies, with outcomes varying by comparator, country, and model settings.Protocol registrationPROSPERO (CRD420251243616).

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Background/Objectives: Standard treatment of multiply relapsed Ewing sarcoma remains to be established. Recent studies evaluating tyrosine kinase inhibitors (TKIs) with anti-angiogenic properties have shown encouraging results. Therefore, we conducted a systematic review and meta-analysis to explore the efficacy and safety of TKIs in patients with Ewing sarcoma. Methods: We comprehensively searched PubMed, Embase, and Cochrane databases for clinical trials (CTs) and cohort studies assessing TKIs in the treatment of advanced Ewing sarcoma patients who received at least one prior line of therapy. The main outcome was objective response rate (ORR). All analyses were conducted using R software (v.4.2.2), employing random effects models with 95% confidence intervals (CIs). Results: We included 14 studies (seven phase II CT and seven retrospective cohorts), comprising 257 patients. The following TKIs were evaluated: cabozantinib, regorafenib, apatinib, anlotinib, sorafenib, lenvatinib, sunitinib, fruquintinib, and imatinib. In a pooled analysis of all Ewing sarcoma patients treated with TKIs, the ORR was 23% (95% CI, 11.2-37.1%) and the DCR was 61.1% (95% CI, 47.3-74.2%). Responses were numerically higher but statistically nonsignificant between clinical trials and real-world studies. The analysis including only single-agent TKIs showed better responses for anlotinib and apatinib, yet these drugs are not available in Western countries. Among the FDA-approved TKIs, superior outcomes were noted with single-agent cabozantinib. (ORR: 21.6%) and regorafenib (ORR: 11.3%). Several studies did not report toxicity data exclusively for Ewing sarcoma patients; thus, conclusions about toxicity are mostly based on the general population of studies and may not be fully representative of Ewing sarcoma patients. Conclusions: Anti-angiogenic TKIs have shown important anti-tumoral activity in patients with Ewing sarcoma. Efficacy was consistently seen in both clinical trials and real-world studies. Nonetheless, there are important differences in study design and population that may limit our interpretation of efficacy and toxicity findings.

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