dc.contributor.author | Martin, M | |
dc.contributor.author | Zielinski, C | |
dc.contributor.author | Ruiz-Borrego, M | |
dc.contributor.author | Carrasco, E | |
dc.contributor.author | Turner, N | |
dc.contributor.author | Ciruelos, EM | |
dc.contributor.author | Muñoz, M | |
dc.contributor.author | Bermejo, B | |
dc.contributor.author | Margeli, M | |
dc.contributor.author | Anton, A | |
dc.contributor.author | Kahan, Z | |
dc.contributor.author | Csöszi, T | |
dc.contributor.author | Casas, MI | |
dc.contributor.author | Murillo, L | |
dc.contributor.author | Morales, S | |
dc.contributor.author | Alba, E | |
dc.contributor.author | Gal-Yam, E | |
dc.contributor.author | Guerrero-Zotano, A | |
dc.contributor.author | Calvo, L | |
dc.contributor.author | de la Haba-Rodriguez, J | |
dc.contributor.author | Ramos, M | |
dc.contributor.author | Alvarez, I | |
dc.contributor.author | Garcia-Palomo, A | |
dc.contributor.author | Huang Bartlett, C | |
dc.contributor.author | Koehler, M | |
dc.contributor.author | Caballero, R | |
dc.contributor.author | Corsaro, M | |
dc.contributor.author | Huang, X | |
dc.contributor.author | Garcia-Sáenz, JA | |
dc.contributor.author | Chacón, JI | |
dc.contributor.author | Swift, C | |
dc.contributor.author | Thallinger, C | |
dc.contributor.author | Gil-Gil, M | |
dc.date.accessioned | 2021-01-22T10:39:48Z | |
dc.date.issued | 2021-03-15 | |
dc.identifier.citation | Annals of oncology : official journal of the European Society for Medical Oncology, 2020 | |
dc.identifier.issn | 0923-7534 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/4306 | |
dc.identifier.eissn | 1569-8041 | |
dc.identifier.doi | 10.1016/j.annonc.2020.12.013 | |
dc.description.abstract | 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. | |
dc.format | Print-Electronic | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | ELSEVIER | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0 | |
dc.title | 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. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2020-12-17 | |
rioxxterms.versionofrecord | 10.1016/j.annonc.2020.12.013 | |
rioxxterms.licenseref.uri | https://creativecommons.org/licenses/by/4.0 | |
rioxxterms.licenseref.startdate | 2020-12-29 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | Annals of oncology : official journal of the European Society for Medical Oncology | |
pubs.notes | Not known | |
pubs.organisational-group | /ICR | |
pubs.organisational-group | /ICR/Primary Group | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Breast Cancer Research | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Breast Cancer Research/Molecular Oncology | |
pubs.organisational-group | /ICR | |
pubs.organisational-group | /ICR/Primary Group | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Breast Cancer Research | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Breast Cancer Research/Molecular Oncology | |
pubs.publication-status | Published | |
pubs.embargo.terms | Not known | |
icr.researchteam | Molecular Oncology | |
dc.contributor.icrauthor | Turner, Nicholas | |