| Title: |
Effectiveness comparison of first-line CDK4/6 inhibitors in patients with hormone-positive HER2-negative advanced breast cancer according to tumor histology: a sub-analysis of the real-world, multicenter, Italian study PALMARES-2 |
| Authors: |
Mazzoli, Giacomo; Provenzano, Leonardo; Dieci, Maria Vittoria; Curigliano, Giuseppe; Giuliano, Mario; Botticelli, Andrea; Lambertini, Matteo; Rizzo, Gianpiero; Pedersini, Rebecca; Sirico, Marianna; La Verde, Nicla; Gennari, Alessandra; Zambelli, Alberto; Toss, Angela; Piras, Marta; Giordano, Monica; Tagliaferri, Barbara; Generali, Daniele; Sartori, Donata; Fotia, Giuseppe; De Monte, Matteo; Ligorio, Francesca; Jacobs, Flavia; Armani, Giovanna; Zurlo, Christian; Menichetti, Alice; Griguolo, Gaia; Faso, Valeria; Schianca, Ambra Carnevale; Munzone, Elisabetta; Marra, Antonio; Chiappe, Edoardo; Scagnoli, Simone; Pisegna, Simona; Capasso, Camilla; De Angelis, Carmine; Arpino, Grazia; Criscitiello, Carmen; Guarneri, Valentina; Pruneri, Giancarlo; Mariani, Luigi; the PALMARES-2 study group; Vernieri, Claudio |
| Contributors: |
G. Mazzoli; L. Provenzano; M.V. Dieci; G. Curigliano; M. Giuliano; A. Botticelli; M. Lambertini; G. Rizzo; R. Pedersini; M. Sirico; N. La Verde; A. Gennari; A. Zambelli; A. To; M. Pira; M. Giordano; B. Tagliaferri; D. Generali; D. Sartori; G. Fotia; M. De Monte; F. Ligorio; F. Jacob; G. Armani; C. Zurlo; A. Menichetti; G. Griguolo; V. Faso; A.C. Schianca; E. Munzone; A. Marra; E. Chiappe; S. Scagnoli; S. Pisegna; C. Capasso; C. De Angeli; G. Arpino; C. Criscitiello; V. Guarneri; G. Pruneri; L. Mariani; G. the PALMARES-2 study; C. Vernieri |
| Publisher Information: |
Churchill Livingstone |
| Publication Year: |
2026 |
| Collection: |
The University of Milan: Archivio Istituzionale della Ricerca (AIR) |
| Subject Terms: |
CDK4/6 inhibitor; HR+/HER2-advanced breast cancer; Histology; Inverse probability of treatment weighting; Lobular; PALMARES-2; Real-world; Settore MEDS-09/A - Oncologia medica |
| Description: |
Introduction: Invasive lobular breast cancer (ILC) is the second most common breast cancer subtype, with distinctive biological and epidemiologic features. Although phase III trials of cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) in hormone receptor-positive, HER2-negative advanced breast cancer (HR+/HER2-aBC) included patients with ILC, their real-world effectiveness in this population remains poorly characterized. Material and methods: In this sub-analysis of the multicenter, real-world PALMARES-2 study (NCT06805812), we assessed the predictive and prognostic value of lobular histology in HR+/HER2-aBC treated with first-line endocrine therapy (ET) plus CDK4/6i. The primary endpoint was real-world progression-free survival (rwPFS). Associations between histology and outcomes were adjusted for 15 covariates using multivariable Cox-regression and inverse probability of treatment weighting. Results: Among 1982 patients, 367 (18.5 %) had ILC and 1481 (74.7 %) non-special type (NST). Median follow-up was 29.8 and 31.2 months, respectively. ILC was associated with shorter rwPFS versus NST (adjusted hazard ratio [aHR]: 1.24, 95 %CI:1.04–1.47, P=0.017). Palbociclib efficacy was not affected by lobular histology (P for interaction = 0.553) while abemaciclib was less effective in ILC (P = 0.009). All three CDK4/6i achieved similar rwPFS in ILC (ribociclib vs palbociclib: aHR: 1.01, 95 %CI: 0.67–1.45, P = 0.949; abemaciclib vs palbociclib: aHR: 1.13, 95 %CI: 0.75–1.71, P = 0.551; abemaciclib vs ribociclib: aHR: 1.15, 95 %CI: 0.73–1.80, P = 0.549). Conclusions: Tumor histology affects the real-world effectiveness of first line ET plus CDK4/6i. In ILC, all three CDK4/6i performed similarly; therefore, treatment selection should prioritize tolerability, manageability, drug-drug interactions, and patient preferences. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
info:eu-repo/semantics/altIdentifier/pmid/41619649; info:eu-repo/semantics/altIdentifier/wos/WOS:001682628000001; volume:86; firstpage:1; lastpage:11; numberofpages:11; journal:BREAST; https://hdl.handle.net/2434/1219635 |
| DOI: |
10.1016/j.breast.2026.104692 |
| Availability: |
https://hdl.handle.net/2434/1219635; https://doi.org/10.1016/j.breast.2026.104692 |
| Rights: |
info:eu-repo/semantics/openAccess ; license:Creative commons ; license uri:http://creativecommons.org/licenses/by-nc-nd/4.0/ |
| Accession Number: |
edsbas.596047E8 |
| Database: |
BASE |