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, PhD^1,2,3; 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, PhD^10,11; Vega Iranzo, MD, PhD^12,13; Duncan Wheatley, MD, PhD¹⁴; Sonia del Barco Berrón, MD, PhD¹⁵; Antonio Antón, MD, PhD^16,17; Erion Dobi, MD, PhD¹⁸; Manuel Ruiz-Borrego, MD, PhD¹⁹; Daniel Alcalá-López, PhD¹; Jhudit Pérez-Escuredo, PhD¹; Gabriele Antonarelli, MD, PhD^20,21; Miguel Sampayo-Cordero, PhD¹; José Manuel Pérez-García, MD, PhD^1,22; Javier Cortés, MD, PhD^1,22,23,24;

Source: DOI:10.1200/JCO-24-01865

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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