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.
