Real-world treatment patterns and outcomes during and after treatment with CDK4/6 inhibitors for HR-positive and HER2-negative metastatic breast cancer.

Abstract

e13052 Background: The purpose of this multicenter study was to investigate treatment patterns and real-world outcomes among patients with hormone receptor-positive and human epidermal growth factor 2 receptor-negative (HR+/HER2-) metastatic breast cancer (MBC) treated with cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i) in northwest China. Methods: Patients with HR+/HER2- MBC who received CDK4/6i for the first time between July 2017 and December 2024 at 11 centers were retrospectively included. Results: A total of 605 women were eligible for analysis, including 398 (67.2%), 126 (21.3%), and 68 (11.5%) who received CDK4/6i therapy as first-, second-, and third- or later-line treatment, respectively. The median PFS was 22.9 months (95% CI, 19.6-26.7 months). The earlier the CDK4/6i was used, the longer the mPFS was achieved (first-line 26.6 vs second-line 21.0 vs later-line 11.0 months, P = 0.00014). The data on at least two consecutive lines’ treatment after progression on CDK4/6i were available for 225 patients. The first post-CDK4/6i regimen was chemotherapy (CT), endocrine therapy (ET), or antibody–drug conjugates (ADC) in 121 (53.8%), 88 (39.1%), and 16 (7.1%) patients, respectively, with different mPFSb observed among the three group (CT 5.67 vs ET 9.20 vs ADC 10.03 months, P = 0.00029). Among all different sequential treatment combinations, there was a statistically significant difference in mPFS3 across different treatment regimens in the cohort that selected ET after progression on CDK4/6i (CDK4/6i→ET→ET 32.93 vs CDK4/6i→ET→CT 23.53 vs CDK4/6i→ET→ADC 33.67 months, P = 0.0017). Conclusions: Our findings support the early initiation of CDK4/6i plus ET in patients. After progression on CDK4/6i, ET should be preferred for patients maintaining endocrine sensitivity, otherwise ADC especially for HER2-low patients, whereas CT should be delayed as much as clinical feasible, as it seems that CT may weaken the efficacy of its subsequent ET or ADC. Patterns of post-progression therapy with CDK4/6i in different lines. All patients (n = 225) 1st line (n = 144) 2nd line (n=55) ≥ 3rd line (n=26) P CT 121 (53.8) 70 (48.6) 35 (63.6) 16 (61.7) 0.027 Taxanes 75 (33.3) 47 (32.6) 23 (41.8) 5 (19.3) Three-bines* 17 (7.6) 9 (6.3) 6 (10.9) 2 (7.7) Utidelone/Eribulin/others 29 (12.9) 14 (9.7) 6 (10.9) 9 (34.7) ET 88 (39.1) 64 (44.4) 16 (29.1) 8 (30.7) 0.041 Single SERD 11 (4.8) 6 (4.1) 4 (7.3) 1 (3.8) ET + overline CDK4/6i Palbociclib 11 (4.8) 8 (5.7) 2 (3.6) 1 (3.8) Abemaciclib 25 (11.1) 15 (10.4) 5 (9.1) 5 (19.3) Ribociclib 17 (7.6) 15 (10.4) 2 (3.6) 0 (0.0) Dalpiciclib 17 (7.6) 13 (9.0) 3 (5.5) 1 (3.8) PAM inhibitor* + FUL/AI 7 (3.2) 7 (4.8) 0 (0.0) 0 (0.0) ADC 16 (7.1) 10 (7.0) 4 (7.3) 2 (7.6) 0.73 *three-bines including Gemcitabine, Vinorelbine, or Capecitabine *PAM inhibitor including PI3K inhibitors, AKT inhibitors, mTOR inhibitors, etc.