000100717 001__ 100717 000100717 005__ 20230519145418.0 000100717 0247_ $$2doi$$a10.1016/j.annonc.2020.12.013 000100717 0248_ $$2sideral$$a123397 000100717 037__ $$aART-2021-123397 000100717 041__ $$aeng 000100717 100__ $$aMartin, M. 000100717 245__ $$aPalbociclib 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 000100717 260__ $$c2021 000100717 5060_ $$aAccess copy available to the general public$$fUnrestricted 000100717 5203_ $$aBackground: 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. 000100717 540__ $$9info:eu-repo/semantics/openAccess$$aby-nc-nd$$uhttp://creativecommons.org/licenses/by-nc-nd/3.0/es/ 000100717 590__ $$a51.769$$b2021 000100717 592__ $$a8.59$$b2021 000100717 594__ $$a47.3$$b2021 000100717 591__ $$aONCOLOGY$$b5 / 245 = 0.02$$c2021$$dQ1$$eT1 000100717 593__ $$aMedicine (miscellaneous)$$c2021$$dQ1 000100717 593__ $$aHematology$$c2021$$dQ1 000100717 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion 000100717 700__ $$aZielinski, C. 000100717 700__ $$aRuiz-Borrego, M. 000100717 700__ $$aCarrasco, E. 000100717 700__ $$aTurner, N. 000100717 700__ $$aCiruelos, E.M. 000100717 700__ $$aMuñoz, M. 000100717 700__ $$aBermejo, B. 000100717 700__ $$aMargeli, M. 000100717 700__ $$0(orcid)0000-0002-9159-4988$$aAnton, A.$$uUniversidad de Zaragoza 000100717 700__ $$aKahan, Z. 000100717 700__ $$aCsöszi, T. 000100717 700__ $$aCasas, M.I. 000100717 700__ $$aMurillo, L. 000100717 700__ $$aMorales, S. 000100717 700__ $$aAlba, E. 000100717 700__ $$aGal-Yam, E. 000100717 700__ $$aGuerrero-Zotano, A. 000100717 700__ $$aCalvo, L. 000100717 700__ $$ade la Haba-Rodriguez, J. 000100717 700__ $$aRamos, M. 000100717 700__ $$aAlvarez, I. 000100717 700__ $$aGarcia-Palomo, A. 000100717 700__ $$aHuang Bartlett, C. 000100717 700__ $$aKoehler, M. 000100717 700__ $$aCaballero, R. 000100717 700__ $$aCorsaro, M. 000100717 700__ $$aHuang, X. 000100717 700__ $$aGarcia-Sáenz, J.A. 000100717 700__ $$aChacón, J.I. 000100717 700__ $$aSwift, C. 000100717 700__ $$aThallinger, C. 000100717 700__ $$aGil-Gil, M. 000100717 7102_ $$11007$$2610$$aUniversidad de Zaragoza$$bDpto. Medicina, Psiqu. y Derm.$$cArea Medicina 000100717 773__ $$g32, 4 (2021), 488-499$$pAnn. oncol.$$tANNALS OF ONCOLOGY$$x0923-7534 000100717 8564_ $$s488551$$uhttps://zaguan.unizar.es/record/100717/files/texto_completo.pdf$$yVersión publicada 000100717 8564_ $$s3258238$$uhttps://zaguan.unizar.es/record/100717/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada 000100717 909CO $$ooai:zaguan.unizar.es:100717$$particulos$$pdriver 000100717 951__ $$a2023-05-18-14:04:02 000100717 980__ $$aARTICLE