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

Martin, M. ; Zielinski, C. ; Ruiz-Borrego, M. ; Carrasco, E. ; Turner, N. ; Ciruelos, E.M. ; Muñoz, M. ; Bermejo, B. ; Margeli, M. ; Anton, A. (Universidad de Zaragoza) ; Kahan, Z. ; Csöszi, T. ; Casas, M.I. ; 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, J.A. ; Chacón, J.I. ; Swift, C. ; Thallinger, C. ; Gil-Gil, M.

Resumen: 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.

Idioma: Inglés

DOI: 10.1016/j.annonc.2020.12.013

Año: 2021

Publicado en: ANNALS OF ONCOLOGY 32, 4 (2021), 488-499
ISSN: 0923-7534

Factor impacto JCR: 51.769 (2021)

Categ. JCR: ONCOLOGY rank: 5 / 245 = 0.02 (2021) - Q1 - T1

Factor impacto CITESCORE: 47.3 - Medicine (Q1)

Factor impacto SCIMAGO: 8.59 - Medicine (miscellaneous) (Q1) - Hematology (Q1)

Tipo y forma: Artículo (Versión definitiva)

Área (Departamento): Area Medicina (Dpto. Medicina, Psiqu. y Derm.)