Article
作者: Zurlo, Christian ; Chiappe, Edoardo ; Mariani, Luigi ; Sartori, Donata ; Pedersini, Rebecca ; Jacobs, Flavia ; Gennari, Alessandra ; Armani, Giovanna ; De Angelis, Carmine ; Criscitiello, Carmen ; Giordano, Monica ; Vernieri, Claudio ; Menichetti, Alice ; Sirico, Marianna ; Griguolo, Gaia ; Schianca, Ambra Carnevale ; Toss, Angela ; Rizzo, Gianpiero ; Ligorio, Francesca ; Marra, Antonio ; Capasso, Camilla ; Tagliaferri, Barbara ; Provenzano, Leonardo ; Scagnoli, Simone ; Guarneri, Valentina ; Curigliano, Giuseppe ; Arpino, Grazia ; Dieci, Maria Vittoria ; Faso, Valeria ; Piras, Marta ; Botticelli, Andrea ; Munzone, Elisabetta ; Generali, Daniele ; Fotia, Giuseppe ; La Verde, Nicla ; Pisegna, Simona ; Giuliano, Mario ; De Monte, Matteo ; Mazzoli, Giacomo ; Pruneri, Giancarlo ; Lambertini, Matteo ; Zambelli, Alberto
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.