125 research outputs found
Overall Survival with Palbociclib and Fulvestrant in Advanced Breast Cancer
BACKGROUND
The cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor palbociclib, in combination with fulvestrant therapy, prolongs progression-free survival among patients
with hormone-receptor–positive, human epidermal growth factor receptor 2
(HER2)–negative advanced breast cancer. We report the results of a prespecified
analysis of overall survival.
METHODS
We randomly assigned patients with hormone-receptor–positive, HER2-negative
advanced breast cancer who had progression or relapse during previous endocrine
therapy to receive palbociclib plus fulvestrant or placebo plus fulvestrant. We analyzed overall survival; the effect of palbociclib according to the prespecified
stratification factors of presence or absence of sensitivity to endocrine therapy,
presence or absence of visceral metastatic disease, and menopausal status; the efficacy of subsequent therapies after disease progression; and safety.
RESULTS
Among 521 patients who underwent randomization, the median overall survival
was 34.9 months (95% confidence interval [CI], 28.8 to 40.0) in the palbociclib–
fulvestrant group and 28.0 months (95% CI, 23.6 to 34.6) in the placebo–fulvestrant group (hazard ratio for death, 0.81; 95% CI, 0.64 to 1.03; P=0.09; absolute
difference, 6.9 months). CDK4/6 inhibitor treatment after the completion of the
trial regimen occurred in 16% of the patients in the placebo–fulvestrant group.
Among 410 patients with sensitivity to previous endocrine therapy, the median
overall survival was 39.7 months (95% CI, 34.8 to 45.7) in the palbociclib–fulvestrant group and 29.7 months (95% CI, 23.8 to 37.9) in the placebo–fulvestrant
group (hazard ratio, 0.72; 95% CI, 0.55 to 0.94; absolute difference, 10.0 months).
The median duration of subsequent therapy was similar in the two groups, and
the median time to the receipt of chemotherapy was 17.6 months in the palbociclib–
fulvestrant group, as compared with 8.8 months in the placebo–fulvestrant group
(hazard ratio, 0.58; 95% CI, 0.47 to 0.73; P<0.001). No new safety signals were
observed with 44.8 months of follow-up.
CONCLUSIONS
Among patients with hormone-receptor–positive, HER2-negative advanced breast
cancer who had sensitivity to previous endocrine therapy, treatment with palbociclib–fulvestrant resulted in longer overall survival than treatment with placebo–
fulvestrant. The differences in overall survival in the entire trial group were not
significant. (Funded by Pfizer; PALOMA-3 ClinicalTrials.gov number, NCT01942135.
Overall survival (OS) with palbociclib plus fulvestrant in women with hormone receptor-positive (HR1), human epidermal growth factor receptor 2-negative (HER22) advanced breast cancer (ABC): Analyses from PALOMA-3
Background: Endocrine therapy (ET)–resistant ABC is dependent on cyclin dependent
kinase (CDK) 4/6. In the prospective, randomized, double-blind, phase 3 PALOMA-3
study, the CDK4/6 inhibitor PAL in combination with FUL significantly improved progression-free survival (PFS) vs placebo (PBO)þFUL (median PFS, 11.2 vs 4.6 mo; absolute difference, 6.6 mo; hazard ratio [HR] 0.50 [95% CI, 0.40–0.62]; P < 0.000001).
Here, we report OS analysis with a median follow up of 44.8 mo.
Methods: HRþ/HER2– ABC (N ¼ 521) patients (pts) who had relapsed or progressed
on prior ET were randomized 2:1 to PAL (125 mg/d orally, schedule 3/1) þ FUL
(500 mg per standard of care) or PBOþFUL. Primary endpoint was investigator-assessed PF
Refined histopathological predictors of BRCA1 and BRCA2 mutation status: A large-scale analysis of breast cancer characteristics from the BCAC, CIMBA, and ENIGMA consortia
Introduction: The distribution of histopathological features of invasive breast tumors in BRCA1 or BRCA2 germline mutation carriers differs from that of individuals with no known mutation. Histopathological features thus have utility for mutation prediction, including statistical modeling to assess pathogenicity of BRCA1 or BRCA2 variants of uncertain clinical significance. We analyzed large pathology datasets accrued by the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA) and the Breast Cancer Association Consortium (BCAC) to reassess histopathological predictors of BRCA1 and BRCA2 mutation status, and provide robust likelihood ratio (LR) estimates for statistical modeling. Methods: Selection criteria for study/center inclusion were estrogen receptor (ER) status or grade data available for invasive breast cancer diagnosed younger than 70 years. The dataset included 4,477 BRCA1 mutation carriers, 2,565 BRCA2 mutation carriers, and 47,565 BCAC breast cancer cases. Country-stratified estimates of the
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