Entry Detail
| General information | |
| Database: | DB01080 |
| Objective: | Growth of hormonereceptorpositive breast cancer is dependent on cyclindependent kinases 4 and 6 (CDK4 and CDK6), which promote progression from the G1phase to the Sphase of the cell cycle. They assessed the efficacy of palbociclib (an inhibitor of CDK4 and CDK6) and fulvestrant in advanced breast cancer. |
| Authors: | Turner NC, et al |
| Title: | Palbociclib in HormoneReceptorPositive Advanced Breast Cancer. |
| Journal: | N Engl J Med. |
| Year: | 2015 |
| PMID: | 26030518 |
| Trial Design | |
| Clinical Trial Id: | NCT01942135 |
| Agent: | palbociclib |
| Target: | Cell division protein kinase 6 Cell division protein kinase 4 |
| Cancer Type: | breast cancer |
| Cancer Subtype: | human epidermal growth factor receptor 2positive advanced breast cancer |
| Therapy Type: | com |
| Therapeutic Combination Type: | 2 |
| Therapeutic Combination Content: | palbociclib+ fulvestrant |
| Study Type: | a doubleblind, phase III study |
| Key Patients Feature: | patients with advanced hormonereceptorpositive, human epidermal growth factor receptor 2negative breast cancer that had relapsed or progressed during prior endocrine therapy |
| Biomarker: | HormoneReceptorPositive |
| Biomark Analysis: | NA |
| Control Group Info: | placebo+ fulvestrant |
| Treatment Info: | patients were randomly assigned in a 2:1 ratio to receive palbociclib (125 mg per day orally for 3 weeks, followed by 1 week off) and fulvestrant (500 mg intramuscularly per standard of care every 14 days for the first three injections and then every 28 days) or matching placebo and fulvestrant. |
| Primary End Point: | investigatorassessed progression free survival. |
| Secondary End Point: | overall survival, objective response, rate of clinical benefit, patientreported outcomes, and safety. |
| Patients Number: | 521 |
| Trial Results | |
| DLT_MTD: | NA |
| Objective Response Rate: | Rates of overall objective response were 10.4% (95% CI, 7.4 to 14.1) with palbociclib-fulvestrant and 6.3% (95% CI, 3.2 to 11.0) with placebo-fulvestrant (P=0.16). |
| Disease Control Rate: | The rate of clinical benefit (response or prolonged stable disease) at the interim analysis was 34.0% (95% CI, 29.0 to 39.3) with palbociclib-fulvestrant and 19.0% (95% CI, 13.4 to 25.6) with placebo-fulvestrant (P<0.001). |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | The median progression free survival was 9.2 months (95% confidence interval [CI], 7.5 to not estimable) with palbociclibfulvestrant and 3.8 months (95% CI, 3.5 to 5.5) with placebofulvestrant (hazard ratio for disease progression or death, 0.42; 95% CI, 0.32 to 0.56; P<0.001). |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | The most common grade 3 or 4 adverse events in the palbociclibfulvestrant group were neutropenia (62.0%, vs. 0.6% in the placebofulvestrant group), leukopenia (25.2% vs. 0.6%), anemia (2.6% vs. 1.7%), thrombocytopenia (2.3% vs. 0%), and fatigue (2.0% vs. 1.2%). Febrile neutropenia was reported in 0.6% of palbociclibtreated patients and 0.6% of placebotreated patients. The rate of discontinuation due to adverse events was 2.6% with palbociclib and 1.7% with placebo. |
| Conclusions: | Among patients with hormonereceptorpositive metastatic breast cancer who had progression of disease during prior endocrine therapy, palbociclib combined with fulvestrant resulted in longer progression free survival than fulvestrant alone |