1. Randomized phase II study of fulvestrant plus palbociclib or placebo in endocrine-sensitive, hormone receptor-positive/HER2–advanced breast cancer: GEICAM/2014–12 (FLIPPER).
- Author
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Albanell, J., Martínez, M.T., Ramos, M., O'Connor, M., de la Cruz-Merino, L., Santaballa, A., Martínez-Jañez, N., Moreno, F., Fernández, I., Alarcón, J., Virizuela, J.A., de la Haba-Rodríguez, J., Sánchez-Rovira, P., González-Cortijo, L., Margelí, M., Sánchez-Muñoz, A., Antón, A., Casas, M., Bezares, S., and Rojo, F.
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THERAPEUTIC use of antineoplastic agents , *SAMPLE size (Statistics) , *CONFIDENCE intervals , *LEUCOPENIA , *PROTEIN kinase inhibitors , *ESTRADIOL , *EPIDERMAL growth factor , *CELL receptors , *NEUTROPENIA , *TREATMENT effectiveness , *RANDOMIZED controlled trials , *LYMPHOPENIA , *BLIND experiment , *POSTMENOPAUSE , *SURVIVAL analysis (Biometry) , *DESCRIPTIVE statistics , *ANEMIA , *FATIGUE (Physiology) , *BREAST tumors , *DRUG resistance in cancer cells , *DISEASE complications - Abstract
The potential benefit of adding palbociclib to fulvestrant as first-line treatment in hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative endocrine-sensitive advanced breast cancer (ABC) patients remains uncharacterized. In this randomized (1:1), double-blind, phase II study, postmenopausal women with HR-positive, HER2-negative ABC with de novo metastatic disease or those who relapsed after >12 months of adjuvant endocrine therapy received palbociclib/fulvestrant or placebo/fulvestrant. Stratification was based on recurrent versus de novo metastatic disease and visceral involvement. The primary objective was one-year progression-free survival (PFS-1y) rate. The sample size was 190 patients. The two-sided alpha of 0.2, 80% of power to detect a difference between the arms, assuming PFS rates of 0.695 and 0.545 for palbociclib/fulvestrant and placebo/fulvestrant, respectively. In total, 189 patients were randomized to palbociclib/fulvestrant ([ n = 94] or placebo/fulvestrant [ n = 95]). 45.5% and 60.3% of patients had de novo metastatic disease and visceral involvement, respectively. PFS-1y rates were 83.5% and 71.9% in the palbociclib/fulvestrant and placebo/fulvestrant arms, (HR 0.55, 80% CI 0.36–0.83, P = 0.064). The median PFS were 31.8 and 22.0 months for the palbociclib/fulvestrant and placebo/fulvestrant arms (aHR 0.48, 80% CI 0.37–0.64, P = 0.001). The most frequent grade 3–4 adverse events were neutropenia (68.1% vs. 0%), leucopenia (26.6% vs. 0%), anemia (3.2% vs. 0%), and lymphopenia (14.9% vs. 2.1%) for the palbociclib/fulvestrant and placebo/fulvestrant, respectively. The most frequent non-hematologic grade 3–4 adverse event was fatigue (4.3% vs. 0%). Palbociclib/fulvestrant demonstrated better PFS-1y rates and median PFS than placebo/fulvestrant in HR-positive/HER2-negative endocrine-sensitive ABC patients. • Palbociclib + fulvestrant as first-line improved the 1-year PFS rate in ABC patients. • Palbociclib + fulvestrant significantly improved median PFS. • Palbociclib + fulvestrant had a manageable safety profile. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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