In 2022,gastric cancer(GC)ranked as the fifth most common cancer and the third leading cause of cancer death in China,with 358,672 new cases and 260,372 deaths,accounting for 37.0%and 39.4%of global cases,respectively...In 2022,gastric cancer(GC)ranked as the fifth most common cancer and the third leading cause of cancer death in China,with 358,672 new cases and 260,372 deaths,accounting for 37.0%and 39.4%of global cases,respectively[1].Previous studies have shown that 25.9%and 36.5%of GC patients in China were diagnosed at stages III and IV,respectively,with 5-year overall survival(OS)rates of 33.0%for stage III and 5.5%for stage IV[2,3].展开更多
CDK2 is a principal mediator of CDK4/6 resistance.Concurrent CDK2/4/6 blockade may be effective in treating HR-positive,HER2-negative advanced breast cancer(ABC).This randomized,double-blind,parallel-controlled,phase ...CDK2 is a principal mediator of CDK4/6 resistance.Concurrent CDK2/4/6 blockade may be effective in treating HR-positive,HER2-negative advanced breast cancer(ABC).This randomized,double-blind,parallel-controlled,phase 3 trial(ClinicalTrials.gov,NCT05375461)assessed the efficacy of culmerciclib,a CDK2/4/6 inhibitor,plus fulvestrant in ABC.Patients with HR-positive,HER2-negative,locally recurrent or metastatic breast cancer were randomized(2:1)to receive culmerciclib plus fulvestrant or matching placebo plus fulvestrant.Between March 18,2022 and March 3,2023,293 pretreated patients(median age 53.0 years;pre-or perimenopausal 42.3%;bone metastasis 65.2%)were randomized to assigned treatments.At this prespecified interim analysis,culmerciclib plus fulvestrant extended the median investigator-assessed progression-free survival(PFS)significantly,the primary endpoint,as compared with placebo plus fulvestrant(16.6 months,95%CI 13.8 to not evaluable versus 7.5 months,95%CI 5.3 to 11.0;hazard ratio 0.36,95%CI 0.26–0.51;stratified log rank test P<0.001).Consistent effects were observed across diverse subgroups of patients.At a median follow-up duration of 13.8 months,overall survival was immature.The investigators-assessed objective response rate was 40.2%(95%CI,33.3–47.5)for culmerciclib compared to 12.1%(95%CI 6.4–20.2)for placebo(stratified Mantel-Haenszelχ2 test P<0.001).Diarrhea(87.1%)and neutropenia(80.4%)were the most common toxicities with culmerciclib plus fulvestrant.In conclusion,this randomized clinical trial met its primary outcome.Culmerciclib plus fulvestrant is well tolerated and leads to a significant gain in PFS of pretreated HR-positive HER2-negative ABC patients.展开更多
基金approved by the Independent Ethics Committee of Chinese PLA General Hospital(C2021-102-01)Changzhi People’s Hospital(LSPJ2022006)+17 种基金Fujian Provincial Cancer Hospital(2022-016-01)Cancer Hospital of Shandong First Medical University(SDZLEC2022-042-01)The First People’s Hospital of Changde City(2022-016-01)Jilin Cancer Hospital(202201-011-01)Linyi People’s Hospital(2022-lunlishencha-10)Liaoning Cancer Hospital and Institute(20220205)Shanxi Province Cancer Hospital(YW2022009)Affiliated Cancer Hospital of Zhengzhou University,Henan Cancer Hospital(L2022-Y010-002)Harbin Medical University Cancer Hospital(2022-91)Anhui Provincial Cancer Hospital,The First Affiliated Hospital of University of Science and Technology of China(2022-lunlishencha-08)The Fourth Hospital of Hebei Medical University(2022044)Binzhou Medical University Hospital(2022-001-01)Central Hospital Affiliated to Shandong Medical University(jizhongxinlunlilinshen2022-011-01)Qingdao Central Hospital,University of Health and Rehabilitation Science([Y]SY202200401)Liaocheng People’s Hospital(2022006)Suining Central Hospital(2022-lunliyijian-sy002-01)Yanan University Xianyang Hospital(YDXYEC-YWPJ-2022-5)conducted in accordance with the Declaration of Helsinki and Good Clinical Practices.Written informed consent was obtained from all patients before enrollment.
文摘In 2022,gastric cancer(GC)ranked as the fifth most common cancer and the third leading cause of cancer death in China,with 358,672 new cases and 260,372 deaths,accounting for 37.0%and 39.4%of global cases,respectively[1].Previous studies have shown that 25.9%and 36.5%of GC patients in China were diagnosed at stages III and IV,respectively,with 5-year overall survival(OS)rates of 33.0%for stage III and 5.5%for stage IV[2,3].
基金sponsored by the Chia Tai Tianqing Pharmaceutical Group Co.,Ltd.
文摘CDK2 is a principal mediator of CDK4/6 resistance.Concurrent CDK2/4/6 blockade may be effective in treating HR-positive,HER2-negative advanced breast cancer(ABC).This randomized,double-blind,parallel-controlled,phase 3 trial(ClinicalTrials.gov,NCT05375461)assessed the efficacy of culmerciclib,a CDK2/4/6 inhibitor,plus fulvestrant in ABC.Patients with HR-positive,HER2-negative,locally recurrent or metastatic breast cancer were randomized(2:1)to receive culmerciclib plus fulvestrant or matching placebo plus fulvestrant.Between March 18,2022 and March 3,2023,293 pretreated patients(median age 53.0 years;pre-or perimenopausal 42.3%;bone metastasis 65.2%)were randomized to assigned treatments.At this prespecified interim analysis,culmerciclib plus fulvestrant extended the median investigator-assessed progression-free survival(PFS)significantly,the primary endpoint,as compared with placebo plus fulvestrant(16.6 months,95%CI 13.8 to not evaluable versus 7.5 months,95%CI 5.3 to 11.0;hazard ratio 0.36,95%CI 0.26–0.51;stratified log rank test P<0.001).Consistent effects were observed across diverse subgroups of patients.At a median follow-up duration of 13.8 months,overall survival was immature.The investigators-assessed objective response rate was 40.2%(95%CI,33.3–47.5)for culmerciclib compared to 12.1%(95%CI 6.4–20.2)for placebo(stratified Mantel-Haenszelχ2 test P<0.001).Diarrhea(87.1%)and neutropenia(80.4%)were the most common toxicities with culmerciclib plus fulvestrant.In conclusion,this randomized clinical trial met its primary outcome.Culmerciclib plus fulvestrant is well tolerated and leads to a significant gain in PFS of pretreated HR-positive HER2-negative ABC patients.
