%0 Journal Article
%A Martin, M
%A Zielinski, C
%A Ruiz-Borrego, M
%A Carrasco, E
%A Turner, N
%A Ciruelos, E M
%A Muñoz, M
%A Bermejo, B
%A Margeli, M
%A Anton, A
%A Kahan, Z
%A Csoszi, T
%A Casas, M I
%A Murillo, L
%A Morales, S
%A Alba, E
%A Gal-Yam, E
%A Guerrero-Zotano, A
%A Calvo, L
%A de-la-Haba-Rodriguez, J
%A Ramos, M
%A Alvarez, I
%A Garcia-Palomo, A
%A Huang-Bartlett, C
%A Koehler, M
%A Caballero, R
%A Corsaro, M
%A Huang, X
%A Garcia-Saenz, J A
%A Chacon, J I
%A Swift, C
%A Thallinger, C
%A Gil-Gil, M
%T Palbociclib in combination with endocrine therapy versus capecitabine in hormonal receptor-positive, human epidermal growth factor 2-negative, aromatase inhibitor-resistant metastatic breast cancer: a phase III randomised controlled trial-PEARL.
%D 2020
%U http://hdl.handle.net/10668/16888
%X Palbociclib plus endocrine therapy (ET) is the standard treatment of hormone receptor-positive and human epidermal growth factor receptor 2-negative, metastatic breast cancer (MBC). However, its efficacy has not been compared with that of chemotherapy in a phase III trial. PEARL is a multicentre, phase III randomised study in which patients with aromatase inhibitor (AI)-resistant MBC were included in two consecutive cohorts. In cohort 1, patients were randomised 1 : 1 to palbociclib plus exemestane or capecitabine. On discovering new evidence about estrogen receptor-1 (ESR1) mutations inducing resistance to AIs, the trial was amended to include cohort 2, in which patients were randomised 1 : 1 between palbociclib plus fulvestrant and capecitabine. The stratification criteria were disease site, prior sensitivity to ET, prior chemotherapy for MBC, and country of origin. Co-primary endpoints were progression-free survival (PFS) in cohort 2 and in wild-type ESR1 patients (cohort 1 + cohort 2). ESR1 hotspot mutations were analysed in baseline circulating tumour DNA. From March 2014 to July 2018, 296 and 305 patients were included in cohort 1 and cohort 2, respectively. Palbociclib plus ET was not superior to capecitabine in both cohort 2 [median PFS: 7.5 versus 10.0 months; adjusted hazard ratio (aHR): 1.13; 95% confidence interval (CI): 0.85-1.50] and wild-type ESR1 patients (median PFS: 8.0 versus 10.6 months; aHR: 1.11; 95% CI: 0.87-1.41). The most frequent grade 3-4 toxicities with palbociclib plus exemestane, palbociclib plus fulvestrant and capecitabine, respectively, were neutropenia (57.4%, 55.7% and 5.5%), hand/foot syndrome (0%, 0% and 23.5%), and diarrhoea (1.3%, 1.3% and 7.6%). Palbociclib plus ET offered better quality of life (aHR for time to deterioration of global health status: 0.67; 95% CI: 0.53-0.85). There was no statistical superiority of palbociclib plus ET over capecitabine with respect to PFS in MBC patients resistant to AIs. Palbociclib plus ET showed a better safety profile and improved quality of life.
%K HER2-negative
%K Capecitabine
%K Endocrine therapy
%K Hormone receptor-positive
%K Metastatic breast cancer
%K Palbociclib
%~