Efficacy Of Fruquintinib Research Articles

Early Local Community Data on Safety and Efficacy of Fruquintinib in Metastatic Colorectal Cancer

Early Local Community Data on Safety and Efficacy of Fruquintinib in Metastatic Colorectal Cancer

A phase Ⅰ/Ⅱa study of cetuximab combined with fruquintinib in the previously treated RAS/BRAF wild-type metastatic colorectal cancer: Results of the CEFRU study.

e15558 Background: The standard third-line treatment for mCRC is regorafenib, fruquintinib or TAS-102. However, the efficacy was not satisfied. Since VEGF and EGFR share the downstream signaling pathway, targeting these two pathways may have synergistic efficacy. The phase Ib trial with regorafenib combined with cetuximab have shown preliminary benefit. Fruquintinib is a small molecule highly selective VEGFR1/2/3 molecule inhibitor. Here, we evaluate the safety and efficacy of fruquintinib plus cetuximab in previously treated RAS/BRAF wild-type mCRC. Methods: This is an open-label phase I/IIa study. The primary objective was to determine the recommended phase 2 dose (RP2D) in a 3+3 dose escalation strategy in phase I and safety, grade 3/4 adverse events in phase IIa. Secondary objectives include ORR, mPFS, and mOS. Eligible patients were diagnosed as advanced RAS/BRAF wild-type CRC and had received at least two prior regimens of standard therapies. Exclude patients who have previously used other small molecule anti-vascular inhibitors. The planned number of cases is 20(including phaseⅠandⅡa). ChiCTR2000038227. Results: Between Sep, 2020 to Sep, 2022, 21 pts were enrolled including 7 patients of phase Ⅰ. The RP2D is fruquintinib 4 mg QD (3 weeks on/1 week off) plus cetuximab 500mg/m2 every two weeks, received by 17 pts. Two patient dropped out，one because of refusing treatment and another due to severe allergic reaction. 15 pts were included in the efficacy analysis and 16 pts in the safety analysis. The left side mCRC accounted for 87.5%. 68.8% have received cetuximab and 75% have received bevacizumab. The overall TRAE was 75.0%, with 25.0% grade 3 or above. The most common treatment-related AEs were acneiform rash, hypoproteinemia and dry skin (Table1). One patient had dose reduction of fruquintinib due to acneiform rash. Evaluation in 15 treated patients showed 2 cases were PR, 10 were SD and 3 were PD. DCR was 80%. mPFS was 128 days(95%CI:49.7-206.3). mOS was 229 days(95%CI: 104.0-354.0). Conclusions: Cetuximab combined with fruquintinib showed promising anti-tumor activity in CRC with resistance to at least two prior regimens. The toxicity was tolerable and no unexpected toxicities were observed (Table 1). Clinical trial information: Clinical trial information: ChiCTR2000038227 . [Table: see text]

Efficacy and safety of fruquintinib as third- or further-line therapy for patients with advanced bone and soft tissue sarcoma: a multicenter retrospective study.

Fruquintinib is an oral small-molecule angiogenesis inhibitor, markedly specifically inhibited vascular endothelial growth factor 2 (VEGFR2). This retrospective study aimed to evaluate the safety and efficacy of fruquintinib, or in combination with immunotherapy or chemotherapy in patients with bone and soft tissue sarcoma (STS), who have failed at least secondary-line treatment. We performed a retrospective analysis of advanced bone and STS patients who received fruquintinib containing third- or further-line therapy in Shanghai Jiao Tong University Affiliated Sixth People's and the Affiliated Hospital of Jiangxi University of Traditional Chiese Medicine from September 2019 to February 2022. All of them had accepted at least anthracyclines-based chemotherapy. For the experimental group, 25 cases, the patients took a basic dose of fruquintinib 3-5 mg once a day for 21 days per 4 weeks as a cycle until the disease progression or intolerable toxicity. The other 20 patients in the control group received the best supportive care. The patients were evaluated by computed tomography (CT) or MRI once 2 months or symptoms worse. The DCR, progression-free survival (PFS), and adverse reactions of the drug were recorded and reviewed. The DCR in patients receiving fruquintinib therapy was 80.0%. The median PFS (mPFS) in the fruquintinib-containing therapy group was significantly longer than that in the control group (4.8 vs. 1.4 months; P < 0.001). The mPFS in the fruquintinib group, the fruquintinib-OI group and the fruquintinib-chemotherapy group were 3.2 months [95% confidence interval (CI), 2.0-7.9], 4.9 months (95% CI, 3.0-9.9) and 4.2 months (95% CI, 2.6-6.6) respectively, all of them were longer than the mPFS of 1.4 months (95% CI, 0.3-2.5) in the control group (P < 0.001). Fruquintinib was reported for the first time to have favorable efficacy and safety as an optional treatment for patients with advanced bone and STS who failed in multi-line therapies.

An observational study of dose-optimization for fruquintinib in elderly patients (pts) with metastatic colorectal cancer (mCRC) who had failed standard therapy.

e15560 Background: As one of the third-line standard treatment regimens for advanced colorectal cancer, fruquintinib is widely used in clinical practice, but there are limited data on safety and efficacy of fruquintinib in elderly pts. Multiple studies have shown improved tolerability, reduced grade 3-4 adverse events, and comparable efficacy in pts treated with regorafenib through a first-cycle flexible dose optimization regimen. This method of drug administration is more practical especially in elderly pts, and is worthy of clinical adoption. This observational study aims to investigate the safety, tolerability, and efficacy of a dose-optimized regimen of fruquintinib in elderly mCRC pts who had failed previous standard therapy. Methods: Pts ≥65 years with mCRC refractory to fluoropyrimidine-based chemotherapy ± anti-VEGF/EGFR were enrolled. The primary endpoint was progression-free survival (PFS) (RECIST v1.1). All pts were administered with fruquintinib 3mg (po, qd) for one week. If tolerable, fruquintinib 4mg would be administered in the second week. In the third week, fruquintinib 5mg would be administered if 4mg is tolerable, followed by a week’s rest. The maximum tolerated dose (MTD) of fruquintinib confirmed in the first cycle would be administered from the second cycle. Adverse events were evaluated using CTCAE 5.0. Results: As of February 9, 2022, 29 pts were identified, with an median age of 69.59 (65-77) years and 16 males (55.2%) included. Of the 29 pts, the MTD was 3mg in 31% (9/29) pts, 4mg in 58.6% (17/29) pts and 5mg in 10.3% (3/29) pts. Among the 24 pts available for efficacy evaluation, 14 had stable disease (SD) and 10 had progressive disease (PD) as the best response. Disease control rate (DCR) of 3mg group, 4mg group and 5mg group were 33.33% (2/6), 68.75% (11/16) and 50.00% (1/2), respectively. At a median 4.93 months follow-up, the median (m) PFS was 3.73 months [95% CI, 2.32-5.14] and the mOS was 7.97 months [95% CI, 5.05-10.89]. In addition, the median PFS of 3mg group and 4mg group were 1.87 months and 3.73 months, respectively. And the median OS of 3mg group and 4mg group was 7.97 months and 11.0 months, respectively. Treatment-related adverse events (TRAEs) were observed in all 29 pts (100%). Common TRAEs (&gt; 40%) included fatigue (79.3%), anorexia (58.6%) and hand-foot syndrome (44.8%). The most common (&gt; 10%) grade≥3TRAEs were hand-foot syndrome (20.7%), hypertension (17.2%) and diarrhea (10.3%). No grade 5 TRAEs were observed. There were no correlations with efficacy, toxicity, and geriatric assessment scores. Conclusions: The dose-optimized strategy of fruquintinib in pts aged ≥ 65 years showed acceptable toxicities and anti-tumor activities consistent with the overall population in FRESCO study. The dose-optimized strategy of fruquintinib is a viable alternative in older pts with mCRC. Clinical trial information: NCT05025631.

485P A phase Ib study of cetuximab combined with fruquintinib in the previously treated RAS/BRAF wild-type metastatic colorectal cancer: The preliminary result of CEFRU study

The standard third-line treatment of metastatic colorectal cancer (mCRC) is regorafenib, fruquintinib, or TAS-102. However, the efficacy was not satisfied. We conducted a phase Ib /Ⅱa clinical study to evaluate the safety and efficacy of fruquintinib plus cetuximab in mCRC（TPS151, 2021 ASCO GI） This time we reported the phase Ib dose-escalation study results.

337TiP An open-label, phase Ib/II study to evaluate the safety and efficacy of fruquintinib in combination with tislelizumab in patients with advanced triple-negative breast cancer

Immune checkpoint inhibitors (ICIs) have improved clinical outcomes in triple-negative breast cancer (TNBC), but many patients (pts) do not respond to ICIs or will develop resistance. Combining VEGFR inhibition may potentiate ICI efficacy by normalizing vascular immune crosstalk and improving immune effector cell infiltration. Tislelizumab (T) is a humanized, IgG4-variant monoclonal antibody against PD-1. Fruquintinib (F) is a novel, highly selective, oral, tyrosine kinase inhibitor of VEGFR-1, 2, 3.

Subgroup Analysis by Liver Metastasis in the FRESCO Trial Comparing Fruquintinib versus Placebo Plus Best Supportive Care in Chinese Patients with Metastatic Colorectal Cancer.

ObjectiveThe aim of the present subgroup analysis of the FRESCO trial is to determine the efficacy and hepatotoxicity of fruquintinib in Chinese patients with metastatic CRC with liver metastasis (CRLM) who were receiving third-line or posterior-line therapy.MethodsOverall survival (OS) and progression-free survival (PFS) were evaluated by Kaplan–Meier method. Hazard ratio (HR) was estimated through Cox proportional hazards model. Hepatotoxicity was coded using the standardized MedDRA queries of hepatic failure, fibrosis, cirrhosis, and other liver injury-related conditions and graded using the Common Terminology Criteria Adverse Events grades. The efficacy of fruquintinib in patients with CRLM was evaluated in various subgroups.ResultsA total of 287 (69.0%) patients with metastatic CRC had liver metastasis (LM, fruquintinib: 185 and placebo: 102). Median OS in patients with CRLM was significantly prolonged with fruquintinib compared with placebo (8.61 months vs 5.98 months; HR=0.59, 95% CI, 0.45–0.77, P<0.001). In patients with CRLM, the incremental median PFS for patients in the fruquintinib-treated group was significantly higher than in the placebo group (median PFS: 3.71 vs.1.84 months; HR=0.22, 95% CI: 0.17–0.30; P<0.001). Compared with placebo, significant improvements in OS were observed with fruquintinib in LM patients regardless of lung metastasis, prior target therapy, and K-RAS status. In patients with CRLM, treatment-emergent hepatotoxicities of any grade occurred in 7 (3.8%) patients in the fruquintinib group vs 2 (2.0%) in the placebo group.ConclusionFruquintinib demonstrated a statistically significant increase in OS and PFS as compared with placebo in Chinese patients with CRLM. The hepatotoxicity of fruquintinib was less reported, and comparable with placebo in patients with CRLM.ClinicalTrials.gov IdentifierNCT02314819.

A phaseⅠ/Ⅱa clinical study of cetuximab combined with fruquintinib in the third-line treatment of RAS/BRAF wild-type colorectal cancer.

TPS151 Background: The standard third-line treatment of mCRC is regofenib, fruquintinib or TAS-102. However, the efficacy was not satisfied. Because VEGF and EGFR share the downstream signal pathway, targeting these two pathways may have synergistic efficacy. Preclinical studies have confirmed the effect of the combination of regorafenib and cetuximab. The subsequent phase Ⅰb study in advanced cancer showed the combination is effective. Fruquintinib is the same anti-VEGF drugs and was approved in China. Our department has treated one patient of advanced colorectal cancer, no standard regimen after third-line treatment. The efficacy is SD and PFS time exceeded 6 months. Therefore this study explores the safety and efficacy of fruquintinib combined with cetuximab. Methods: This is a single-center, non-random, prospective, open exploratory study. Eligible pts were diagnosed as advanced RAS/BRAF wild-type colorectal cancer and had received at least two prior regimens of standard therapies. The purpose of phase Ⅰ is to confirm the safety and the appropriate dose of fruquintinib combined with cetuximab. The phase Ⅱa investigate the safety and the efficacy of fruquintinib combined with cetuximab. Phase I: The dose of cetuximab is 500mg/m2 every two weeks which is clinically tolerable, so the dose need not be adjusted. fruquintinib is taken once daily for the first 21 days of each 28-day cycle and the dose adjustment is required due to the side effects. The standard dose of fruquintinib is 5mg/d, but the side effects are serious. The dose of 3mg/d is the minimum effective dose, therefore the initial dose of fruquintinib starts from 4mg, and three patients are enrolled. If DLT appeared in less than three patients, the dose elevated to 5mg/d. Three patients were enrolled in the 5mg/d dose group. If DLT appeared in less than three patients, the right dose of fruquintinib was 5mg/d. If DLT appeared in all three patients of the 5mg/d, fruquintinib was declined to 4mg/d combined with cetuximab to carry out a phase Ⅱa study. Fruquintinib initial dose is 4mg/d. If DLT was present in all three patients, the dose was reduced to 3mg/d. The standard dose of fruquintinib (3mg/d) was determined to be MDT, and the subsequent phase Ⅱa study was conducted by giving fruquintinib 3mg/d. The phase Ⅱa study is cetuximab 500mg/m2 biweekly combined with fruquintinib according to the confirmed dose in phase Ⅰ, taking it once daily for the first 21 days of each 28-day cycle. The number of cases is 20.Response assessment via CT/MRI is to be done q8 wks (RECIST 1.1). Continue until disease progression or unacceptable toxicity. The primary objective is to estimate safety, grade 3/4 adverse, and DLT. Secondary objectives include ORR, PFS, and OS. Final analysis to be done 6 mo after enrollment of the final pt. Clinical trial information: ChiCTR2000038227 . Research Sponsor: None