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.
CDK4/6i in the Underrepresented Histological Subtypes of HR±/HER2- Metastatic Breast Cancer: A Real-World Cohort Study of Effectiveness and Safety
Poggio, Francesca;Del Mastro, Lucia;
2026-01-01
Abstract
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.
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