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
Year: 2026
Type: article
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.
Source: The Breast
Authors: Francesca Ligorio, Leonardo Provenzano, Giuseppe Fotia, Maria Vittori Dieci, Giuseppe Curigliano, Mario Giuliano, Andrea Botticelli, Matteo Lambertini, Gianpiero Rizzo, Rebecca Pedersini, Marianna Sirico, Nicla La Verde, Alessandra Gennari, Alberto Zambelli, Angela Toss, Marta Piras, Monica Giordano, Barbara Tagliaferri, Daniele Generali, Donata Sartori, Giacomo Mazzoli, Flavia Jacobs, Giovanna Armani, Caterina Sposetti, Christian Zurlo, Alice Menichetti, Gaia Griguolo, Valeria Faso, Laura Boldrini, Elisabetta Munzone, Antonio Marra, Edoardo Chiappe, Simone Scagnoli, Simona Pisegna, Camilla Capasso, Carmine De Angelis, Grazia Arpino, Carmen Criscitiello, Valentina Guarneri, Giancarlo Pruneri, Luigi Mariani, Gianpaolo Bianchini, Daniela Miliziano, Matteo De Monte, Chiara Corti, Pier Paolo Berton Giachetti, Ambra Carnevale Schianca, Jalissa Katrini, Maria Silvia Cona, Vincenza Cantile, Angela Grieco, Miriam Pirolo, Maria Zappulo, Maria Anna Rachele De Giglio, Marta Laganà, Deborah Cosentini, Ugo De Giorgi, Andrea Vingiani, Antonino Belfiore, Alice Abate, Valentina Bianchessi, Giuseppe Capri, Giulia Valeria Bianchi, Filippo de Braud, Paolo Baili, Ilaria Cavallo, Cristina Ferraris, Gabriele Martelli, Secondo Folli, Gianfranco Scaperrotta, Catherine Depretto, Angioletta Lasagna, Ornella Ponzoni, Stefano Maccarone, Carla Strina, Silvia Coccato, Rosalinda Coviello, Claudio Vernieri
Institutions: IFOM, Fondazione IRCCS Istituto Nazionale dei Tumori, University of Milan, University of Padua, Istituto Oncologico Veneto, European Institute of Oncology, Federico II University Hospital, University of Naples Federico II, Sapienza University of Rome, Ospedale Policlinico San Martino, University of Genoa, Policlinico San Matteo Fondazione, Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, Luigi Sacco Hospital, ASST Fatebenefratelli Sacco, Università degli Studi del Piemonte Orientale “Amedeo Avogadro”, Azienda Ospedaliero Universitaria Maggiore della Carita, Ospedale Papa Giovanni XXIII, University of Milano-Bicocca, University of Modena and Reggio Emilia, Azienda Ospedaliero-Universitaria di Modena, IRCCS Ospedale San Raffaele, Azienda Socio Sanitaria Territoriale Lariana, Istituti Clinici Scientifici Maugeri, University of Trieste, Azienda Socio Sanitaria Territoriale di Cremona, Ospedale di Mirano, Dana-Farber Cancer Institute, Azienda Ospedaliera Sant'Andrea, Istituto Nazionale Tumori IRCCS "Fondazione G. Pascale", IRCCS Humanitas Research Hospital, Vita-Salute San Raffaele University, University of Salento, Ospedale Vito Fazzi
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,200
OpenAlex ID: W7143626367