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.
Date
2021-03-15ICR Author
Author
Martin, M
Zielinski, C
Ruiz-Borrego, M
Carrasco, E
Turner, N
Ciruelos, EM
Muñoz, M
Bermejo, B
Margeli, M
Anton, A
Kahan, Z
Csöszi, T
Casas, MI
Murillo, L
Morales, S
Alba, E
Gal-Yam, E
Guerrero-Zotano, A
Calvo, L
de la Haba-Rodriguez, J
Ramos, M
Alvarez, I
Garcia-Palomo, A
Huang Bartlett, C
Koehler, M
Caballero, R
Corsaro, M
Huang, X
Garcia-Sáenz, JA
Chacón, JI
Swift, C
Thallinger, C
Gil-Gil, M
Type
Journal Article
Metadata
Show full item recordAbstract
BACKGROUND: 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. PATIENTS AND METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.
Collections
Research team
Molecular Oncology
Language
eng
Date accepted
2020-12-17
License start date
2020-12-29
Citation
Annals of oncology : official journal of the European Society for Medical Oncology, 2020
Publisher
ELSEVIER