Background: Metastatic colorectal cancer(mCRC) patients with progressive disease after all available standard therapies need new medication for further treatment. Famitinib is a small-molecule multikinase inhibitor, w...Background: Metastatic colorectal cancer(mCRC) patients with progressive disease after all available standard therapies need new medication for further treatment. Famitinib is a small-molecule multikinase inhibitor, with promising anticancer activities. This multicenter, randomized, double-blinded, placebo-controlled, phase II clinical trial was designed to evaluate the safety and efficacy of famitinib in mCRC.Methods: Famitinib or placebo was administered orally once daily. The primary endpoint was progression-free survival(PFS). Secondary endpoints included objective response rate(ORR), disease control rate(DCR), overall survival(OS), quality-of-life(QoL), and safety.Results: Between July 18,2012 and Jan 22,2014, a total of 167 patients were screened, and 154 patients were randomized in a 2:1 ratio to receive either famitinib(n = 99) or placebo(n = 55). The median PFS was 2.8 and 1.5 months in the famitinib and placebo groups(hazard ratio = 0.60,95% confidence interval = 0.41-0.86, P = 0.004). The DCR was 59.8% and 31.4%(P = 0.002) and the ORR was 2.2% and 0.0%(P = 0.540) in the famitinib and placebo groups,respectively. The most frequent grade 3-4 adverse events were hypertension(11.1%), hand-foot syndrome(10.1%),thrombocytopenia(10.1%) and neutropenia(9.1%). Serious adverse events occurred in 11(11.1%) patients in the famitinib group and 5(9.1%) in the placebo group(P = 0.788). The median OS of the famitinib and placebo groups was 7.4 and 7.2 months(P = 0.657).Conclusion: Famitinib prolonged PFS in refractory mCRC patients with acceptable tolerability.Trial registration This study was registered on ClinicalTrials.gov(NCT01762293) and was orally presented in the 2015 ASCO-Gastrointestinal展开更多
Concurrent inhibition of angiogenesis and immune checkpoints represents a potent therapeutic approach.We conducted a phase 2,multicenter,basket study to assess the efficacy and safety of combination therapy of famitin...Concurrent inhibition of angiogenesis and immune checkpoints represents a potent therapeutic approach.We conducted a phase 2,multicenter,basket study to assess the efficacy and safety of combination therapy of famitinib(anti-angiogenic agent)plus camrelizumab(PD-1 antagonist)in patients with metastatic solid tumors across 11 cohorts(this study was registered at Clinicaltrials.gov[NCT04346381]).This report focuses on the cohort of patients with metastatic or advanced colorectal cancer.Eligible patients,who had previously received R2 lines of systemic treatments for their metastatic disease,were treated with famitinib(20 mg once daily)in combination with camrelizumab(200 mg intravenously every 3 weeks).The primary endpoint was the objective response rate,with secondary endpoints encompassing progressionfree survival,overall survival,duration of response,safety and exploratory biomarkers.A total of 44 patients were enrolled and treated.With a median follow-up time of 9.46 months(range 2.0-22.5 months),objective responses were observed in 6 patients(13.6%;95%confidence interval[CI],5.2%-27.4%),all of whom had rectal cancer.The median duration of response is 6.2 months(95%CI,2.3-10.6 months).Median progression-free survival was 3.3 months(95%CI,2.1-4.1 months),and median overall survival was 10.9 months(95%CI,7.6-15.2 months).Among the 44 patients,29(65.9%)experienced grade 3 or 4 treatment-related adverse events,predominantly hypertension and proteinuria.In conclusion,the combination of famitinib and camrelizumab demonstrates promising antitumor activity with a manageable safety profile in metastatic colorectal cancer patients.Further research is warranted to confirm and extend these findings.展开更多
Background Famitinib is a novel and potent multitargeting receptor tyrosine kinase inhibitor. The phase I clinical study showed that famitinib was well tolerated and had a broad anti-tumor spectrum. The purpose of thi...Background Famitinib is a novel and potent multitargeting receptor tyrosine kinase inhibitor. The phase I clinical study showed that famitinib was well tolerated and had a broad anti-tumor spectrum. The purpose of this study was to examine the efficacy and safety of famitinib for the treatment of metastatic renal cell carcinoma （mRCC）. Methods The data of famitinib in treating patients with mRCC from the single-center phases I and II clinical trials were analyzed. Famitinib was administered orally at the dose of 13-30 mg once daily until tumor progression, occurrence of intolerable adverse reactions or withdrawal of the informed consent. Results A total of 24 patients with mRCC were treated including 17 patients at a dose of 25 mg once daily, 4 patients at a dose of 27 mg and 1 patient each at a dose of 13 rag, 20 mg and 30 mg, respectively. Twelve （50.0%） patients achieved partial response （PR） and 9 patients achieved stable disease （SD）. Progressive disease was found in 3 （12.5%） patients. The disease control rate was 87.5%. The median follow-up time was 17.6 months; the median progression free survival （PFS） was 10.7 （95% CI 7.0-14.4） months; and the estimated median overall survival （OS） time was 33.0 （95% CI 8.7-57.3） months. The adverse drug reactions mainly included hypertension （54.1%）, hand-foot skin reactions （45.8%）, diarrhea （33.3%）, mucositis （29.2%）, neutropenia （45.8%）, thrombocytopenia （29.2%）, hyperlipidemia （41.7%） and proteinuria （41.7%）. The incidence rate of grades 3 and 4 adverse events was low, mainly including hypertension 12.5%, hand-foot skin reactions 4.2%, neutropenia 4.2%, thrombocytopenia 4.2%, hyperlipidemia 4.2% and proteinuria 12.5%. Conclusions Famitinib has significant anti-tumor activity in mRCC. The common adverse reactions are generally manageable.展开更多
Background:Famitinib is a tyrosine kinase inhibitor against multiple targets,including vascular endothelial growth factor receptor 2/3,platelet-derived growth factor receptor,and stem cell factor receptor(c-kit).Previ...Background:Famitinib is a tyrosine kinase inhibitor against multiple targets,including vascular endothelial growth factor receptor 2/3,platelet-derived growth factor receptor,and stem cell factor receptor(c-kit).Previous studies have demonstrated anti-tumour activities of famitinib against a wide variety of advanced-stage solid cancers.We aimed to determine the safety and efficacy of famitinib with concurrent chemoradiotherapy(CCRT)in patients with locoregionally advanced nasopharyngeal carcinoma(NPC).We also evaluated the feasibility of contrast-enhanced ultrasound(D-CEUS)as a predictor of early tumour response to famitinib and to correlate functional parameters with clinical efficacy.Methods:The trial was conducted in subjects with stage III or IVa-b NPC using a 3+3 design of escalating fami-tinib doses.Briefly,subjects received 2 weeks of famitinib monotherapy followed by 7 weeks of famitinib plus CCRT.D-CEUS of the neck lymph nodes was performed at day 0,8 and 15 after famitinib was administered before starting concurrent chemoradiotherapy.End points included safety,tolerability and anti-tumour activity.Results:Twenty patients were enrolled(six each for 12.5,16.5 and 20 mg and two for 25 mg).Two patients in the 25 mg cohort developed dose-limiting toxicities,including grade 4 thrombocytopenia and grade 3 hypertension.The most common grade 3/4 adverse events were leukopenia,neutropenia and radiation mucositis.D-CEUS tests showed that more than 60%of patients achieved a perfusion parameter response after 2 weeks taking famitinib alone,and the parameter response was associated with disease improvement.In the famitinib monotherapy stage,three patients(15%)showed partial responses.The complete response rate was 65%at the completion of treatment and 95%3 months after the treatment ended.After a median follow-up of 44 months,the 3-year progression-free survival(PFS)and distant metastasis-free survival were 70%and 75%,respectively.Subjects with a decrease of perfusion parameter response,such as peak intensity decreased at least 30%after 1 week of famitinib treatment,had higher 3-year PFS(90.9%vs.44.4%,95%CI 73.7%-100%vs.11.9%-76.9%,P<0.001)than those with an increase or a reduction of less than 30%.Conclusions:The recommended famitinib dose for phase II trial is 20 mg with CCRT for patients with local advanced NPC.D-CEUS is a reliable and early measure of efficacy for famitinib therapies.Further investigation is required to confirm the effects of famitinib plus chemoradiotherapy.展开更多
文摘Background: Metastatic colorectal cancer(mCRC) patients with progressive disease after all available standard therapies need new medication for further treatment. Famitinib is a small-molecule multikinase inhibitor, with promising anticancer activities. This multicenter, randomized, double-blinded, placebo-controlled, phase II clinical trial was designed to evaluate the safety and efficacy of famitinib in mCRC.Methods: Famitinib or placebo was administered orally once daily. The primary endpoint was progression-free survival(PFS). Secondary endpoints included objective response rate(ORR), disease control rate(DCR), overall survival(OS), quality-of-life(QoL), and safety.Results: Between July 18,2012 and Jan 22,2014, a total of 167 patients were screened, and 154 patients were randomized in a 2:1 ratio to receive either famitinib(n = 99) or placebo(n = 55). The median PFS was 2.8 and 1.5 months in the famitinib and placebo groups(hazard ratio = 0.60,95% confidence interval = 0.41-0.86, P = 0.004). The DCR was 59.8% and 31.4%(P = 0.002) and the ORR was 2.2% and 0.0%(P = 0.540) in the famitinib and placebo groups,respectively. The most frequent grade 3-4 adverse events were hypertension(11.1%), hand-foot syndrome(10.1%),thrombocytopenia(10.1%) and neutropenia(9.1%). Serious adverse events occurred in 11(11.1%) patients in the famitinib group and 5(9.1%) in the placebo group(P = 0.788). The median OS of the famitinib and placebo groups was 7.4 and 7.2 months(P = 0.657).Conclusion: Famitinib prolonged PFS in refractory mCRC patients with acceptable tolerability.Trial registration This study was registered on ClinicalTrials.gov(NCT01762293) and was orally presented in the 2015 ASCO-Gastrointestinal
基金supported by Jiangsu Hengrui Pharmaceuticals Co.,Ltd.,National Natural Science Foundation of China(82373402,82272775)Shanghai Shen-kang Hospital Development Center(SHDC2022CRT001)+1 种基金Shanghai Rising-Star Program(21QA1401600)the Cancer Center,Zhongshan Hospital(2023XKPT19-RC1).
文摘Concurrent inhibition of angiogenesis and immune checkpoints represents a potent therapeutic approach.We conducted a phase 2,multicenter,basket study to assess the efficacy and safety of combination therapy of famitinib(anti-angiogenic agent)plus camrelizumab(PD-1 antagonist)in patients with metastatic solid tumors across 11 cohorts(this study was registered at Clinicaltrials.gov[NCT04346381]).This report focuses on the cohort of patients with metastatic or advanced colorectal cancer.Eligible patients,who had previously received R2 lines of systemic treatments for their metastatic disease,were treated with famitinib(20 mg once daily)in combination with camrelizumab(200 mg intravenously every 3 weeks).The primary endpoint was the objective response rate,with secondary endpoints encompassing progressionfree survival,overall survival,duration of response,safety and exploratory biomarkers.A total of 44 patients were enrolled and treated.With a median follow-up time of 9.46 months(range 2.0-22.5 months),objective responses were observed in 6 patients(13.6%;95%confidence interval[CI],5.2%-27.4%),all of whom had rectal cancer.The median duration of response is 6.2 months(95%CI,2.3-10.6 months).Median progression-free survival was 3.3 months(95%CI,2.1-4.1 months),and median overall survival was 10.9 months(95%CI,7.6-15.2 months).Among the 44 patients,29(65.9%)experienced grade 3 or 4 treatment-related adverse events,predominantly hypertension and proteinuria.In conclusion,the combination of famitinib and camrelizumab demonstrates promising antitumor activity with a manageable safety profile in metastatic colorectal cancer patients.Further research is warranted to confirm and extend these findings.
文摘Background Famitinib is a novel and potent multitargeting receptor tyrosine kinase inhibitor. The phase I clinical study showed that famitinib was well tolerated and had a broad anti-tumor spectrum. The purpose of this study was to examine the efficacy and safety of famitinib for the treatment of metastatic renal cell carcinoma （mRCC）. Methods The data of famitinib in treating patients with mRCC from the single-center phases I and II clinical trials were analyzed. Famitinib was administered orally at the dose of 13-30 mg once daily until tumor progression, occurrence of intolerable adverse reactions or withdrawal of the informed consent. Results A total of 24 patients with mRCC were treated including 17 patients at a dose of 25 mg once daily, 4 patients at a dose of 27 mg and 1 patient each at a dose of 13 rag, 20 mg and 30 mg, respectively. Twelve （50.0%） patients achieved partial response （PR） and 9 patients achieved stable disease （SD）. Progressive disease was found in 3 （12.5%） patients. The disease control rate was 87.5%. The median follow-up time was 17.6 months; the median progression free survival （PFS） was 10.7 （95% CI 7.0-14.4） months; and the estimated median overall survival （OS） time was 33.0 （95% CI 8.7-57.3） months. The adverse drug reactions mainly included hypertension （54.1%）, hand-foot skin reactions （45.8%）, diarrhea （33.3%）, mucositis （29.2%）, neutropenia （45.8%）, thrombocytopenia （29.2%）, hyperlipidemia （41.7%） and proteinuria （41.7%）. The incidence rate of grades 3 and 4 adverse events was low, mainly including hypertension 12.5%, hand-foot skin reactions 4.2%, neutropenia 4.2%, thrombocytopenia 4.2%, hyperlipidemia 4.2% and proteinuria 12.5%. Conclusions Famitinib has significant anti-tumor activity in mRCC. The common adverse reactions are generally manageable.
基金supported by Jiangsu Hengrui Medicine Co.,Ltd[The National Natural Science Foundation of China(Grant No.81230056)The National Science&Technology Pillar Program during the Twelfth Five-year Plan Period(Grand No.2014BAI09B10+4 种基金The Natural Science Foundation of Guangdong Province(Grand Nos.S2013010012220,2017A030312003)the Science and Technology Project of Guangzhou City,China(Grand No.132000507)The Health&Medical Collaborative Innovation Project of Guangzhou City,China(Grand No.201400000001)The Innovation Team Development Plan of the Ministry of Education(Grand No.IRT_17R110)the Program of Introducing Talents of Discipline to Universities(Grand No.B14035)].
文摘Background:Famitinib is a tyrosine kinase inhibitor against multiple targets,including vascular endothelial growth factor receptor 2/3,platelet-derived growth factor receptor,and stem cell factor receptor(c-kit).Previous studies have demonstrated anti-tumour activities of famitinib against a wide variety of advanced-stage solid cancers.We aimed to determine the safety and efficacy of famitinib with concurrent chemoradiotherapy(CCRT)in patients with locoregionally advanced nasopharyngeal carcinoma(NPC).We also evaluated the feasibility of contrast-enhanced ultrasound(D-CEUS)as a predictor of early tumour response to famitinib and to correlate functional parameters with clinical efficacy.Methods:The trial was conducted in subjects with stage III or IVa-b NPC using a 3+3 design of escalating fami-tinib doses.Briefly,subjects received 2 weeks of famitinib monotherapy followed by 7 weeks of famitinib plus CCRT.D-CEUS of the neck lymph nodes was performed at day 0,8 and 15 after famitinib was administered before starting concurrent chemoradiotherapy.End points included safety,tolerability and anti-tumour activity.Results:Twenty patients were enrolled(six each for 12.5,16.5 and 20 mg and two for 25 mg).Two patients in the 25 mg cohort developed dose-limiting toxicities,including grade 4 thrombocytopenia and grade 3 hypertension.The most common grade 3/4 adverse events were leukopenia,neutropenia and radiation mucositis.D-CEUS tests showed that more than 60%of patients achieved a perfusion parameter response after 2 weeks taking famitinib alone,and the parameter response was associated with disease improvement.In the famitinib monotherapy stage,three patients(15%)showed partial responses.The complete response rate was 65%at the completion of treatment and 95%3 months after the treatment ended.After a median follow-up of 44 months,the 3-year progression-free survival(PFS)and distant metastasis-free survival were 70%and 75%,respectively.Subjects with a decrease of perfusion parameter response,such as peak intensity decreased at least 30%after 1 week of famitinib treatment,had higher 3-year PFS(90.9%vs.44.4%,95%CI 73.7%-100%vs.11.9%-76.9%,P<0.001)than those with an increase or a reduction of less than 30%.Conclusions:The recommended famitinib dose for phase II trial is 20 mg with CCRT for patients with local advanced NPC.D-CEUS is a reliable and early measure of efficacy for famitinib therapies.Further investigation is required to confirm the effects of famitinib plus chemoradiotherapy.
