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

Author(s): Antonio Llombart-Cussac, MD, PhD1,2,3; Catherine Harper-Wynne, MD, PhD4; Antonia Perelló, MD, PhD5; Audrey Hennequin, MD, PhD6; Adela Fernández-Ortega, MD, PhD7; Marco Colleoni, MD, PhD8; Sara Marín, MD, PhD2; Vanesa Quiroga, MD, PhD9; Jacques Medioni, MD, PhD10,11; Vega Iranzo, MD, PhD12,13; Duncan Wheatley, MD, PhD14; Sonia del Barco Berrón, MD, PhD15; Antonio Antón, MD, PhD16,17; Erion Dobi, MD, PhD18; Manuel Ruiz-Borrego, MD, PhD19; Daniel Alcalá-López, PhD1; Jhudit Pérez-Escuredo, PhD1; Gabriele Antonarelli, MD, PhD20,21; Miguel Sampayo-Cordero, PhD1; José Manuel Pérez-García, MD, PhD1,22; Javier Cortés, MD, PhD1,22,23,24;
Source: DOI:10.1200/JCO-24-01865
Original Article
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Dr. Maen Hussein's Thoughts

Adding Palbociclib did not help, revealing that there is no need to continue with different hormonal therapy than the one used in first line. It also added more toxicity.

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.

Author Affiliations

1Medica Scientia Innovation Research (MEDSIR), Barcelona, Spain; 2Hospital Arnau de Vilanova, FISABIO, Valencia, Spain; 3Translational Oncology Group, Medicine Department, Facultad de Ciencias de la Salud, Universidad Cardenal Herrera-CEU, Alfara del Patriarca, Spain; 4Maidstone Hospital – Kent Oncology Centre, Maidstone, United Kingdom; 5Hospital Universitari Son Espases, Palma de Mallorca, Spain; 6Centre Georges François Leclerc, Dijon, France; 7Institut Català d’Oncologia L’Hospitalet (ICO), Barcelona, Spain; 8IEO, Instituto Europeo di Oncologia, IRCCS, Milan, Italy; 9Institut Català d’Oncologia Badalona (ICO), Barcelona, Spain; 10Hôpital Européen Georges Pompidou, Paris, France; 11University Paris Cité, Paris, France; 12Consorci Hospital General Universitari de València, Valencia, Spain; 13Universitat de València, Valencia, Spain; 14Royal Cornwall Hospital NHS Trust, Cornwall, United Kingdom; 15Institut Català d’Oncologia Girona (ICO), Girona, Spain; 16Hospital Universitario Miguel Servet, Zaragoza, Spain; 17Instituto Investigación Sanitaria Aragón (IISA), Universidad de Zaragoza (UNIZAR), Zaragoza, Spain; 18Hôpital Jean Minjoz, Doubs, France; 19Hospital Universitario Virgen del Rocío, Sevilla, Spain; 20Division of New Drugs and Early Drug Development for Innovative Therapies, European Institute of Oncology, IRCCS, Milan, Italy; 21Department of Oncology and Hemato-Oncology (DIPO), University of Milan, Milan, Italy; 22International Breast Cancer Center (IBCC), Pangaea Oncology, Quiron Group, Barcelona, Spain; 23Department of Medicine, Faculty of Biomedical and Health Sciences, Universidad Europea de Madrid, Madrid, Spain; 24IOB Madrid, Hospital Beata María Ana, Madrid, Spain;

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