Albanell, JMartínez, M TRamos, MO'Connor, Mde la Cruz-Merino, LSantaballa, AMartinez-Jañez, NMoreno, FFernandez, IAlarcon, JVirizuela, J Ade la Haba-Rodriguez, JSanchez-Rovira, PGonzalez-Cortijo, LMargeli, MSanchez-Muñoz, AAnton, ACasas, MBezares, SRojo, F2023-05-032023-05-032021-11-06Albanell J, Martínez MT, Ramos M, O'Connor M, de la Cruz-Merino L, Santaballa A, et al. Randomized phase II study of fulvestrant plus palbociclib or placebo in endocrine-sensitive, hormone receptor-positive/HER2-advanced breast cancer: GEICAM/2014-12 (FLIPPER). Eur J Cancer. 2022 Jan;161:26-37http://hdl.handle.net/10668/22170The 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.enAttribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/Breast cancerCDK 4/6Endocrine-sensitiveFirst-lineFulvestrantMetastaticPalbociclibAdultAgedAged, 80 and overBreast NeoplasmsDouble-Blind MethodFemaleFulvestrantHumansMiddle AgedPiperazinesPyridinesresearch article34902765open accessMétodo doble ciegoNeoplasias de la mamaPersona de mediana edadPiperazinasPiridinas10.1016/j.ejca.2021.11.0101879-0852https://doi.org/10.1016/j.ejca.2021.11.010