000161903 001__ 161903 000161903 005__ 20251017144638.0 000161903 0247_ $$2doi$$a10.1200/JCO-24-01865 000161903 0248_ $$2sideral$$a144476 000161903 037__ $$aART-2025-144476 000161903 041__ $$aeng 000161903 100__ $$aLlombart-Cussac, Antonio 000161903 245__ $$aSecond-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 000161903 260__ $$c2025 000161903 5060_ $$aAccess copy available to the general public$$fUnrestricted 000161903 5203_ $$aPurpose. 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. 000161903 540__ $$9info:eu-repo/semantics/openAccess$$aby-nc-nd$$uhttps://creativecommons.org/licenses/by-nc-nd/4.0/deed.es 000161903 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion 000161903 700__ $$aHarper-Wynne, Catherine 000161903 700__ $$aPerelló, Antonia 000161903 700__ $$aHennequin, Audrey 000161903 700__ $$aFernández-Ortega, Adela 000161903 700__ $$aColleoni, Marco 000161903 700__ $$aMarín, Sara 000161903 700__ $$aQuiroga, Vanesa 000161903 700__ $$aMedioni, Jacques 000161903 700__ $$aIranzo, Vega 000161903 700__ $$aWheatley, Duncan 000161903 700__ $$adel Barco Berrón, Sonia 000161903 700__ $$0(orcid)0000-0002-9159-4988$$aAntón, Antonio$$uUniversidad de Zaragoza 000161903 700__ $$aDobi, Erion 000161903 700__ $$aRuiz-Borrego, Manuel 000161903 700__ $$aAlcalá-López, Daniel 000161903 700__ $$aPérez-Escuredo, Jhudit 000161903 700__ $$aAntonarelli, Gabriele 000161903 700__ $$aSampayo-Cordero, Miguel 000161903 700__ $$aPérez-García, José Manuel 000161903 700__ $$aCortés, Javier 000161903 7102_ $$11007$$2610$$aUniversidad de Zaragoza$$bDpto. Medicina, Psiqu. y Derm.$$cArea Medicina 000161903 773__ $$g43, 18 (2025), 2084-2093$$pJ. clin. oncol.$$tJOURNAL OF CLINICAL ONCOLOGY$$x0732-183X 000161903 8564_ $$s944849$$uhttps://zaguan.unizar.es/record/161903/files/texto_completo.pdf$$yVersión publicada 000161903 8564_ $$s2692202$$uhttps://zaguan.unizar.es/record/161903/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada 000161903 909CO $$ooai:zaguan.unizar.es:161903$$particulos$$pdriver 000161903 951__ $$a2025-10-17-14:30:28 000161903 980__ $$aARTICLE