Martin, MiguelZielinski, ChristophRuiz-Borrego, ManuelCarrasco, EvaCiruelos, Eva MMuñoz, MontserratBermejo, BegoñaMargeli, MireiaCsöszi, TiborAnton, AntonioTurner, NicholasCasas, Maria IMorales, SerafinAlba, EmilioCalvo, Lourdesde la Haba-Rodriguez, JuanRamos, ManuelMurillo, LauraSantaballa, AnaAlonso-Romero, Jose LSanchez-Rovira, PedroCorsaro, MassimoHuang, XinThallinger, ChristianeKahan, ZsuzsannaGil-Gil, Miguel2023-05-032023-05-032022-03-07Martín M, Zielinski C, Ruiz-Borrego M, Carrasco E, Ciruelos EM, Muñoz M, et al. Overall survival with palbociclib plus endocrine therapy versus capecitabine in postmenopausal patients with hormone receptor-positive, HER2-negative metastatic breast cancer in the PEARL study. Eur J Cancer. 2022 Jun;168:12-24http://hdl.handle.net/10668/22172An earlier analysis of the PEARL phase III study showed that palbociclib plus endocrine therapy (ET) does not improve progression-free survival (PFS) over capecitabine in aromatase inhibitor-resistant, hormone receptor-positive/human epidermal growth factor receptor 2-negative metastatic breast cancer (MBC) patients. Here, we report the final overall survival (OS) analysis. Postmenopausal patients (N = 601) were randomized 1:1 to capecitabine or palbociclib plus ET (exemestane, Cohort 1; fulvestrant, Cohort 2). OS was analysed in Cohort 2, the wild-type ESR1 population and the overall population. Additionally, we analysed subsequent systemic therapies and explored PFS2 (time from randomization to the end of the first subsequent therapy/death). OS was 31.1 months for palbociclib plus fulvestrant and 32.8 months for capecitabine (adjusted hazard ratio [aHR] 1.10, 95% confidence interval [CI] 0.81-1.50, P = 0.550). In the wild-type ESR1 population, OS was 37.2 months for palbociclib plus ET and 34.8 months for capecitabine (aHR 1.06, 95% CI 0.81-1.37, P = 0.683). In OS analyses, no subgroup showed superiority for palbociclib plus ET over capecitabine. OS in the overall population was 32.6 months for palbociclib plus ET and 30.9 months for capecitabine (P = 0.995). Subsequent systemic therapy was given to 79.8% and 82.9% of patients with palbociclib plus ET and capecitabine, respectively. Median PFS2 was similar between study arms (Cohort 2, P = 0.941; wild-type ESR1 population, P = 0.827). No new safety findings were observed. Palbociclib plus ET did not show a statistically superior OS compared to capecitabine in MBC patients progressing on aromatase inhibitors.enAttribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/CDK4/6 inhibitorCapecitabineEndocrine therapyHER2–negativeHormone receptor-positive metastatic breast cancerOverall survivalPalbociclibAntineoplastic combined chemotherapy protocolsAromatase inhibitorsBreast neoplasmsCapecitabineFemaleFulvestrantHumansPiperazinesPostmenopausePyridinesReceptor, ErbB-2Receptors, estrogenresearch article35429901open accessCapecitabinaInhibidores de la aromatasaNeoplasias de la mamaPiperazinasPiridinasPosmenopausiaProtocolos de quimioterapia combinada Antineoplásica10.1016/j.ejca.2022.03.0061879-0852http://www.ejcancer.com/article/S0959804922001460/pdf