Cyclin-dependent kinases 4 and 6(CDK4/6)inhibitors demonstrated activity in terms of progression-free survival(PFS)in advanced dedifferentiated liposarcoma(DD-LPS),a sarcoma with CDK4 amplification.CDK4 overexpression...Cyclin-dependent kinases 4 and 6(CDK4/6)inhibitors demonstrated activity in terms of progression-free survival(PFS)in advanced dedifferentiated liposarcoma(DD-LPS),a sarcoma with CDK4 amplification.CDK4 overexpression is by far more common than amplification in sarcomas and it might be a rational target for CDK inhibitors.Preclinical investigators of this study found that CDK4 overexpression,while not of CDKN2A,was the most consistent predictive factor for palbociclib efficacy in sarcomas.Advanced adult-type soft-tissue sarcoma,excluding DD-LPS,or bone sarcoma patients,progressing after at least one systemic line,whose tumors overexpressed CDK4,but not CDKN2A at baseline biopsy,were accrued in this single-arm phase II trial(EudraCT number:2016-004039-19).With the main endpoint of a 6-month PFS rate,40%was considered promising in this population.Palbociclib was administered orally at 125 mg/day for 21 days in 28-day cycles.A total of 214 patients with 236 CDK4/CDKN2A determinations were assessed for prescreening,archival material(141),and screening,baseline biopsy(95).There were 28(29%)with favorable mRNA profiles from 95 screened patients at baseline.From 23 enrolled patients,21 evaluable,the 6-month PFS rate was 29%(95%CI 9–48),and there were 6 patients out of 21 with a PFS longer than 6 months.The median PFS and overall survival were 4.2(95%CI 3.6–4.8)and 12(95%CI 8.7–15.4)months,respectively.Translational research showed a significant correlation between CDK4 mRNA and protein expression.Palbociclib was active in a variety of sarcoma subtypes,selected by CDK4/CDKN2A,and deserves further investigation in the sarcoma context.展开更多
文摘Cyclin-dependent kinases 4 and 6(CDK4/6)inhibitors demonstrated activity in terms of progression-free survival(PFS)in advanced dedifferentiated liposarcoma(DD-LPS),a sarcoma with CDK4 amplification.CDK4 overexpression is by far more common than amplification in sarcomas and it might be a rational target for CDK inhibitors.Preclinical investigators of this study found that CDK4 overexpression,while not of CDKN2A,was the most consistent predictive factor for palbociclib efficacy in sarcomas.Advanced adult-type soft-tissue sarcoma,excluding DD-LPS,or bone sarcoma patients,progressing after at least one systemic line,whose tumors overexpressed CDK4,but not CDKN2A at baseline biopsy,were accrued in this single-arm phase II trial(EudraCT number:2016-004039-19).With the main endpoint of a 6-month PFS rate,40%was considered promising in this population.Palbociclib was administered orally at 125 mg/day for 21 days in 28-day cycles.A total of 214 patients with 236 CDK4/CDKN2A determinations were assessed for prescreening,archival material(141),and screening,baseline biopsy(95).There were 28(29%)with favorable mRNA profiles from 95 screened patients at baseline.From 23 enrolled patients,21 evaluable,the 6-month PFS rate was 29%(95%CI 9–48),and there were 6 patients out of 21 with a PFS longer than 6 months.The median PFS and overall survival were 4.2(95%CI 3.6–4.8)and 12(95%CI 8.7–15.4)months,respectively.Translational research showed a significant correlation between CDK4 mRNA and protein expression.Palbociclib was active in a variety of sarcoma subtypes,selected by CDK4/CDKN2A,and deserves further investigation in the sarcoma context.
