2026-04-17T03:25:02Zhttps://recercat.cat/oai/request

oai:recercat.cat:11351/134992025-09-30T02:07:43Zcom_2072_378070com_2072_378040col_2072_378092

2025-09-30T02:07:42Z urn:hdl:11351/13499 Extended follow-up of palbociclib with fulvestrant or letrozole for endocrine-sensitive, hormone receptor-positive/HER2-negative advanced breast cancer in the PARSIFAL trial Pérez-García, José Manuel Gil Gil, Miguel J. Ruiz-Borrego, Manuel Llombart Cussac, Antonio Bellet Ezquerra, Meritxell dalenc, florence Mama - Càncer - Tractament Quimioteràpia combinada Proteïnes quinases - Inhibidors - Ús terapèutic DISEASES::Neoplasms::Neoplasms by Site::Breast Neoplasms Other subheadings::Other subheadings::Other subheadings::/drug therapy ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Therapeutics::Therapeutics::Drug Therapy::Antineoplastic Protocols::Therapeutics::Drug Therapy::Antineoplastic Combined Chemotherapy Protocols CHEMICALS AND DRUGS::Chemical Actions and Uses::Pharmacologic Actions::Molecular Mechanisms of Pharmacological Action::Enzyme Inhibitors::Protein Kinase Inhibitors ENFERMEDADES::neoplasias::neoplasias por localización::neoplasias de la mama Otros calificadores::Otros calificadores::Otros calificadores::/farmacoterapia TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::terapéutica::terapéutica::farmacoterapia::protocolos antineoplásicos::terapéutica::farmacoterapia::protocolos de quimioterapia antineoplásica combinada COMPUESTOS QUÍMICOS Y DROGAS::acciones y usos químicos::acciones farmacológicas::mecanismos moleculares de acción farmacológica::inhibidores enzimáticos::inhibidores de proteínas cinasas Advanced breast cancer; Extended overall survival; Hormone receptor positive/HER2 negative Cáncer de mama avanzado; Supervivencia global prolongada; Receptor hormonal positivo/HER2 negativo Càncer de mama avançat; Supervivència global prolongada; Receptor hormonal positiu/HER2 negatiu Background Cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i) are the mainstay for hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer (ABC). While the approved CDK4/6i have demonstrated significant improvements in progression-free survival (PFS), inconsistencies exist for overall survival (OS) benefits. Here, we report updated efficacy results from PARSIFAL, a randomized phase II study, that evaluated first-line palbociclib with either letrozole or fulvestrant in postmenopausal patients with endocrine-sensitive, HR-positive/HER2-negative ABC. Patients and methods PARSIFAL-LONG was an international, multicenter, observational study that extended follow-up for patients included in PARSIFAL. The primary objective evaluated updated OS of palbociclib combined with endocrine therapy (fulvestrant or letrozole). Secondary objectives included updated investigator-assessed PFS and subsequent antineoplastic therapies. Exploratory endpoints included identification of new clinical prognostic markers for OS, specifically PFS duration. Results A total of 419 of 486 (86.2%) patients from PARSIFAL were included. Median follow-up was 7.3 years (interquartile range 6.7-7.7 years). At data cut-off (8 January 2024), no differences in efficacy were observed between fulvestrant and letrozole for OS (hazard ratio 1.01, 95% confidence interval [CI], 0.80-1.28, P = 0.927) or PFS (hazard ratio 1.06,95% CI, 0.85-1.31, P = 0.612). Median OS for the overall PARSIFAL-LONG population was 61.8 months (95% CI 56.5-68.4 months), representing the highest OS reported to date for palbociclib and aligning with outcomes observed for other CDK4/6i in this setting. Median PFS was 32.6 months (95% CI 27.5-38.1 months). A total of 85 (20.3%) patients were defined as early progressors (PFS ≤ 12 months). These patients had a shorter median post-progression OS than patients who remained progression free at 12 months (18.7 versus 27.4 months; hazard ratio 0.65, P = 0.004). Conclusions Extended analysis from PARSIFAL confirmed no difference between fulvestrant and letrozole when combined with palbociclib for patients with endocrine-sensitive, HR-positive/HER2-negative ABC. Efficacy results were consistent with those reported in the pivotal first-line trials involving CDK4/6i. Progression within the first year on CDK4/6i may indicate a poorer prognosis. This work was supported by Pfizer S.L.U (Madrid, Spain) (no grant number). Fulvestrant was provided by AstraZeneca. 2025-09-30T02:07:42Z 2025-09-30T02:07:42Z 2025-08-07T06:27:39Z 2025-08-07T06:27:39Z 2025-07 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion http://hdl.handle.net/11351/13499 ESMO Open;10(7) https://doi.org/10.1016/j.esmoop.2025.105309 Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ info:eu-repo/semantics/openAccess Elsevier Scientia