Real-world effectiveness of CDK4/6 inhibitors in older patients with HR+/HER2- advanced breast cancer: a sub-analysis of the multicenter, PALMARES-2 study

BACKGROUND: Older patients with Hormone Receptor-positive, HER2-negative advanced breast cancer (HR+/HER2- aBC) are often frailer than younger patients. Endocrine therapy (ET) plus CDK4/6 inhibitors (CDK4/6i) is the standard first-line treatment regardless of age; however, CDK4/6i real-world effectiveness in older patients is unknown. PATIENTS AND METHODS: PALMARES-2 (NCT06805812) is a large real-world study investigating first-line ET plus CDK4/6i effectiveness in HR+/HER2- aBC patients. We compared real-world progression-free survival (rwPFS) between older (>75 years) and younger (≤75 years) patients in the whole study cohort, as well as in palbociclib, ribociclib, or abemaciclib sub-cohorts. Cox regression models and inverse probability of treatment weighting (IPTW) were used to adjust for prognostic covariates. RESULTS: Older patients accounted for 302 (15.2%) of the PALMARES-2 study cohort (n = 1982). Compared with younger patients, older patients were less likely to have ECOG PS 0 or bone-only disease, and more likely to receive palbociclib. At multivariable analysis, older patients had better rwPFS when compared to younger patients (aHR 0.77; 95% CI 0.67-0.90, p = 0.001). In younger patients, ribociclib and abemaciclib were more effective than palbociclib, whereas in older patients palbociclib showed similar effectiveness to abemaciclib and superior effectiveness to ribociclib (p for interaction <0.001). Among patients treated with palbociclib, older patients had improved rwPFS compared with younger patients (aHR 0.69; 95% CI 0.57-0.84, p < 0.001). CONCLUSION: First-line ET plus CDK4/6i is highly effective in older patients with HR+/HER2- aBC. Based on effectiveness and clinical manageability, palbociclib represents a particularly suitable option in this population.

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Journal
The Breast
Published
2026-03-31
DOI
https://doi.org/10.1016/j.breast.2026.104769
Primary Topic
Advanced Breast Cancer Therapies
Type
article
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article

Real-world effectiveness of CDK4/6 inhibitors in older patients with HR+/HER2- advanced breast cancer: a sub-analysis of the multicenter, PALMARES-2 study

Gianpiero Rizzo, Deborah Cosentini, Donata Sartori, Francesca Ligorio et al.
The Breast
Advanced Breast Cancer Therapies
article

Real-world effectiveness of CDK4/6 inhibitors in older patients with HR+/HER2- advanced breast cancer: a sub-analysis of the multicenter, PALMARES-2 study

Gianpiero Rizzo, Deborah Cosentini, Donata Sartori, Francesca Ligorio, G Armani, Maria Silvia Cona, Angela Grieco, Giuseppe Capri, Giulia Bianchi, Valentina Bianchessi, Christian Zurlo, Giacomo Mazzoli, Paolo Baili, Simona Pisegna, Secondo Folli, Angioletta Lasagna, Monica Giordano, Nicla La Verde, Elisabetta Munzone, Vinny Faso, Daniela Miliziano, Ambra Carnevale Schianca, Alessandra Gennari, Caterina Sposetti, Alice Menichetti, Miriam Pirolo, Camilla Capasso, Gianfranco Scaperrotta, Maria Anna Rachele De Giglio, Marianna Sirico, Barbara Tagliaferri, Carla Strina, Gabriele Martelli, Silvia Coccato, Flavia Jacobs, Cristina Ferraris, Gaia Griguolo, Ornella Ponzoni, Stefano Maccarone, Jalissa Katrini, V. Cantile, Laura Boldrini, Ilaria Cavallo, Antonio Marra, Alice Abate, Marta Piras, Matteo De Monte, Edoardo Chiappe, Pier Paolo Berton Giachetti, Valentina Guarneri, Daniele Generali, Giuseppe Fotia, Mario Giuliano, Filippo de Braud, Rebecca Pedersini, Giancarlo Pruneri, Andrea Vingiani, Chiara Corti, Grazia Arpino, Maria Vittori Dieci, Antonino Belfiore, Angela Toss, Simone Scagnoli, Matteo Lambertini, Maria Zappulo, Rosalinda Coviello, Giuseppe Curigliano, Andrea Botticelli, Catherine Depretto, Marta Laganà, Luigi Mariani, Ugo De Giorgi, Leonardo Provenzano, Claudio Vernieri, Carmen Criscitiello, Alberto Zambelli, Carmine De Angelis, Gianpaolo Bianchini
article en

Abstract

BACKGROUND: Older patients with Hormone Receptor-positive, HER2-negative advanced breast cancer (HR+/HER2- aBC) are often frailer than younger patients. Endocrine therapy (ET) plus CDK4/6 inhibitors (CDK4/6i) is the standard first-line treatment regardless of age; however, CDK4/6i real-world effectiveness in older patients is unknown. PATIENTS AND METHODS: PALMARES-2 (NCT06805812) is a large real-world study investigating first-line ET plus CDK4/6i effectiveness in HR+/HER2- aBC patients. We compared real-world progression-free survival (rwPFS) between older (>75 years) and younger (≤75 years) patients in the whole study cohort, as well as in palbociclib, ribociclib, or abemaciclib sub-cohorts. Cox regression models and inverse probability of treatment weighting (IPTW) were used to adjust for prognostic covariates. RESULTS: Older patients accounted for 302 (15.2%) of the PALMARES-2 study cohort (n = 1982). Compared with younger patients, older patients were less likely to have ECOG PS 0 or bone-only disease, and more likely to receive palbociclib. At multivariable analysis, older patients had better rwPFS when compared to younger patients (aHR 0.77; 95% CI 0.67-0.90, p = 0.001). In younger patients, ribociclib and abemaciclib were more effective than palbociclib, whereas in older patients palbociclib showed similar effectiveness to abemaciclib and superior effectiveness to ribociclib (p for interaction <0.001). Among patients treated with palbociclib, older patients had improved rwPFS compared with younger patients (aHR 0.69; 95% CI 0.57-0.84, p < 0.001). CONCLUSION: First-line ET plus CDK4/6i is highly effective in older patients with HR+/HER2- aBC. Based on effectiveness and clinical manageability, palbociclib represents a particularly suitable option in this population.

The BreastVol. 87
Concordia University Wisconsin (US), University of Modena and Reggio Emilia (IT), Università degli Studi del Piemonte Orientale “Amedeo Avogadro” (IT), University of Salento (IT), Vita-Salute San Raffaele University (IT), University of Milan (IT), Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IT), Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia (IT), Fondazione Salvatore Maugeri (IT), Ospedale Papa Giovanni XXIII (IT), Azienda Ospedaliero-Universitaria di Modena (IT), Istituto Oncologico Veneto (IT), Federico II University Hospital (IT), Dana-Farber Cancer Institute (US), Azienda Ospedaliera Sant'Andrea (IT), Azienda Socio Sanitaria Territoriale Lariana (IT), Ospedale di Mirano (IT), Istituto Nazionale Tumori IRCCS "Fondazione G. Pascale" (IT), Ospedale Policlinico San Martino (IT), Policlinico San Matteo Fondazione (IT), Ospedale Vito Fazzi (IT), Fondazione IRCCS Istituto Nazionale dei Tumori (IT), ASST Fatebenefratelli Sacco (IT), Piedmont University (US), IRCCS Humanitas Research Hospital (IT), Istituti Ospitalieri di Cremona (IT), European Institute of Oncology (IT), University of Milano-Bicocca (IT), University of Naples Federico II (IT), Sapienza University of Rome (IT)
European Commission, Ministero della Salute, Associazione Italiana per la Ricerca sul Cancro
Good health and well-being
Openalex Percentile: Top 38%
Advanced Breast Cancer Therapies
DOIOpen Access PDFOpenAlex
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