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.
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 / 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. Toss, M. Piras, M. Giordano, B. Tagliaferri, D. Generali, D. Sartori, G. Fotia, M. De Monte, F. Ligorio, F. Jacobs, 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 Angelis, G. Arpino, C. Criscitiello, V. Guarneri, G. Pruneri, L. Mariani, G. the PALMARES-2 study, C. Vernieri. - In: BREAST. - ISSN 1532-3080. - 86:(2026 Apr), pp. 104692.1-104692.11. [10.1016/j.breast.2026.104692]
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
G. MazzoliPrimo
;L. ProvenzanoSecondo
;G. Curigliano;D. Generali;G. Fotia;M. De Monte;F. Ligorio;V. Faso;A.C. Schianca;A. Marra;C. Criscitiello;G. Pruneri;C. Vernieri
2026
Abstract
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.
| File | Dimensione | Formato | |
|---|---|---|---|
|
1-s2.0-S0960977626000020-main.pdf
accesso aperto
Tipologia:
Publisher's version/PDF
Licenza:
Creative commons
Dimensione
3.07 MB
Formato
Adobe PDF
|
3.07 MB | Adobe PDF | Visualizza/Apri |
Pubblicazioni consigliate
I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
