Second-Line Endocrine Therapy With or Without Palbociclib Rechallenge in Patients With Hormone Receptor–Positive/Human Epidermal Growth Factor Receptor 2–Negative Advanced Breast Cancer: PALMIRA Trial

Llombart-Cussac, Antonio ; Harper-Wynne, Catherine ; Perelló, Antonia ; Hennequin, Audrey ; Fernández-Ortega, Adela ; Colleoni, Marco ; Marín, Sara ; Quiroga, Vanesa ; Medioni, Jacques ; Iranzo, Vega ; Wheatley, Duncan ; del Barco Berrón, Sonia ; Antón, Antonio (Universidad de Zaragoza) ; Dobi, Erion ; Ruiz-Borrego, Manuel ; Alcalá-López, Daniel ; Pérez-Escuredo, Jhudit ; Antonarelli, Gabriele ; Sampayo-Cordero, Miguel ; Pérez-García, José Manuel ; Cortés, Javier

Resumen: Purpose. Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors plus endocrine therapy (ET) represents the standard first-line treatment for patients with hormone receptor–positive/human epidermal growth factor receptor 2–negative (HER2-negative) advanced breast cancer (ABC). However, there is no definitive consensus on the preferred second-line treatment option. The PALMIRA trial investigated whether palbociclib rechallenge with an alternative ET would improve the antitumor activity in patients progressing after a first-line palbociclib-containing regimen.
Methods. This international, randomized, open-label, phase II study enrolled 198 patients with hormone receptor–positive/HER2-negative ABC with disease progression after first-line palbociclib plus ET (aromatase inhibitor or fulvestrant). Patients were eligible if they showed clinical benefit to the previous regimen (response or stable disease ≥24 weeks) or had progressed on a palbociclib-based therapy in the adjuvant setting. Patients were randomly assigned (2:1 ratio) to either palbociclib rechallenge plus second-line ET (fulvestrant or letrozole) or second-line ET alone. Stratification factors were previous ET and visceral involvement. The primary end point was investigator-assessed progression-free survival (PFS).
Results. Between April 2019 and October 2022, 136 and 62 patients were randomly assigned to palbociclib plus ET or ET alone, respectively. Median investigator-assessed PFS was 4.9 months (95% CI, 3.6 to 6.1) with palbociclib plus ET versus 3.6 months (95% CI, 2.5 to 4.2) with ET alone (hazard ratio, 0.84 [95% CI, 0.66 to 1.07]; P = .149). Grade ≥3 treatment-emergent adverse events were higher with palbociclib plus ET (47.4% v 10.0%), without new safety signals.
Conclusion. Palbociclib rechallenge plus an alternative ET did not significantly improve PFS compared with ET alone in patients with hormone receptor–positive/HER2-negative ABC progressing on a first-line palbociclib-based ET regimen.

Idioma: Inglés

DOI: 10.1200/JCO-24-01865

Año: 2025

Publicado en: JOURNAL OF CLINICAL ONCOLOGY 43, 18 (2025), 2084-2093
ISSN: 0732-183X

Tipo y forma: Artículo (Versión definitiva)

Área (Departamento): Area Medicina (Dpto. Medicina, Psiqu. y Derm.)