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
| Autor: | Isabel Alvarez, Miguel Gil-Gil, C Huang Bartlett, Montse Muñoz, Christiane Thallinger, J. de la Haba-Rodríguez, E. Alba, Xin-Yun Huang, A. García-Palomo, Manuel Ramos, Manuel Ruiz-Borrego, Christoph C. Zielinski, Serafin Morales, Jose Ignacio Chacon, Angel Guerrero-Zotano, Tibor Csoszi, M Casas, Eva Carrasco, Mireia Margeli, Massimo Corsaro, Begoña Bermejo, Maria Koehler, Nicholas C. Turner, Antonio Antón, Eva Ciruelos, Lourdes Calvo, Rosalia Caballero, José A. García-Sáenz, L. Murillo, Zsuzsanna Kahán, Einav Nili Gal-Yam, Claire Swift, Miguel Martin |
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| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Oncology EGF Family of Proteins medicine.medical_specialty palbociclib Pyridines Receptor ErbB-2 medicine.drug_class Breast Neoplasms Palbociclib Piperazines Càncer de mama Capecitabine 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Breast cancer Exemestane Internal medicine Antineoplastic Combined Chemotherapy Protocols medicine Humans Hormone therapy Aromatase inhibitor Fulvestrant Aromatase Inhibitors business.industry endocrine therapy Standard treatment capecitabine Hematology medicine.disease Metastatic breast cancer 030104 developmental biology Receptors Estrogen chemistry 030220 oncology & carcinogenesis Cohort Quality of Life hormone receptor-positive metastatic breast cancer business HER2-negative Hormonoteràpia medicine.drug |
| Zdroj: | Dipòsit Digital de la UB Universidad de Barcelona Annals of Oncology r-IGTP. Repositorio Institucional de Producción Científica del Instituto de Investigación Germans Trias i Pujol instname Zaguán. Repositorio Digital de la Universidad de Zaragoza Annals of oncology : official journal of the European Society for Medical Oncology r-INCLIVA. Repositorio Institucional de Producción Científica de INCLIVA Zaguán: Repositorio Digital de la Universidad de Zaragoza Universidad de Zaragoza |
| ISSN: | 0923-7534 1569-8041 |
| Popis: | BACKGROUND: Palbociclib plus endocrine therapy (ET) is the standard treatment for 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 inhibitors (AIs)-resistant MBC were included in two consecutive cohorts. In cohort 1 (C1), patients were randomised 1:1 to palbociclib plus exemestane or capecitabine. On discovering new evidence about oestrogen receptor-1 (ESR1) mutations inducing resistance to AIs, the trial was amended to include cohort 2 (C2), 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 C2 and in wild-type ESR1 patients (C1+C2). ESR1 hotspot mutations were analysed in baseline circulating tumour DNA. RESULTS: From March-2014 to July-2018, 296 and 305 patients were included in C1 and C2, respectively. Palbociclib plus ET was not superior to capecitabine in both C2 (median PFS: 7.5 vs. 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 vs. 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 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. |
| Databáze: | OpenAIRE |
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