Claudia von Arx, Alessandra Calabrese, Michela Piezzo, Vincenzo Di Lauro, Claudia Martinelli, Claudia Calderaio, Margherita Tafuro, Annarita Verrazzo, Raffaella Di Monda, Enrico Magri, Maria Luisa D'aulisio Garigliota, Anna Maria Di Filippo, Roberto Buonaiuto, Giuseppe Buono, Roberta Caputo, Daniela Cianniello, Ivana Cerillo, Stefania Cocco, Rossana Di Rienzo, Francesco Nuzzo, Carmen Pacilio, Martina Pagliuca, Sara Parola, Matilde Pensabene, Francesca Poggio, Carmine De Angelis, Lucia Del Mastro, Michelino De Laurentiis
CDK4/6i represent a safe and effective therapeutic option for mSTBC. Nevertheless, dedicated studies and tailored treatment strategies are warranted to optimize post-CDK4/6i treatment in these subgroups.
BACKGROUND: Metastatic (m) HR-positive/HER2-negative special-type breast cancer (STBC) exhibits distinct biological behaviors compared with no special-type BC (NSTBC), yet their management is largely extrapolated from trials dominated by NSTBC. To improve understanding of real-world (rw) clinical outcomes, this study evaluated the effectiveness of CDK4/6 inhibitors (i) specifically in patients with mSTBC, providing clinical relevant insights into their therapeutic impact.
PATIENTS AND METHODS: This retrospective cohort study included patients with mSTBC treated with first- or second-line CDK4/6i plus endocrine therapy (ET). Real-world progression-free survival (rwPFS) and overall survival (rwOS) were estimated using the Kaplan-Meier method, and differences between subgroups were evaluated using log-rank tests.
RESULTS: From April 2016 to December 2024, 181 patients received CDK4/6i-based therapy. Median rwPFS was 18.2 months (95% CI, 16-22.1) and median rwOS was 58.1 months (95% CI, 49.4-77.4). A statistically significant difference in rwOS was observed between patients treated with aromatase inhibitors + CDK4/6i versus fulvestrant + CDK4/6i (77.4 vs. 42.4 months; unadjusted HR = 2.2; P = .002). No other subgroup analyses demonstrated statistically significant differences. Common adverse events included neutropenia, anemia, and diarrhea; 32% of patients required dose reductions, which did not adversely affect survival outcomes. Following CDK4/6i progression, overall rwPFS2 was 29.7 months (95% CI, 25.9-32.2). Chemotherapy was the most frequently used post-CDK4/6i treatment, while ET combined with an mTOR-inhibitor provided the longest rwPFS2.
CONCLUSION: CDK4/6i represent a safe and effective therapeutic option for mSTBC. Nevertheless, dedicated studies and tailored treatment strategies are warranted to optimize post-CDK4/6i treatment in these subgroups.