Treatment Patterns in Hormone Receptor-Positive Advanced Breast Cancer following Disease Progression on First-Line CDK4/6 Inhibitor + Endocrine Therapy
| Wednesday, August 13, 2025 |
| 1:47 PM - 1:53 PM |
| Ballroom 2 and 3 |
Overview
Dr Carl He
Speaker
Dr Carl He
Physician Trainee
Eastern Health
Treatment Patterns in Hormone Receptor-Positive Advanced Breast Cancer following Disease Progression on First-Line CDK4/6 Inhibitor + Endocrine Therapy
Abstract
Background:
Cyclin-dependent kinase inhibitor + endocrine therapy (CDK4/6i+ET) is standard first-line(1L) treatment for hormone receptor-positive advanced breast cancer (HR+/HER2-ABC). Treatments after 1L-progression vary, with limited trial data to inform treatment selection. This retrospective study evaluates patterns of second-line(2L) and beyond treatment in patients with HR+ABC.
Methods:
Data was retrieved from ARORA, a multi-centre Australian registry capturing patient, tumour, treatment and outcome information for patients with HR+/HER2-ABC. Patients who received 2L-treatment after failure of 1L CDK4/6i+ET were included. Univariate and multivariate analyses were conducted with SPSS. Correlation was assessed with Chi-square and Fisher’s exact testing, with Log-rank for survival analyses.
Results:
454 patients diagnosed with HR+/HER2-ABC from 1/1/2020-9/9/2024 were enrolled in ARORA, with 300 receiving 1L CDK4/6i+ET. 72(16%) patients who received 1L CDK4/6i+ET had experienced progression, and initiated 2L treatment at time of analysis and were included.
Median follow-up from ABC diagnosis was 39.2 months. Median age of 2L patients was 61.5 years(range 34-85). 39%(n=28) received 2L-chemotherapy and 26%(n=19) received 2L-fulvestrant. 35%(n=25) received other treatment, including 8%(n=6) CDK4/6i+fulvestrant, 3%(n=2) everolimus, 6%(n=4) AKT-inhibitor, 1%(n=1) PIK3CA-inhibitor and 1%(n=1) clinical trial. Greater 2L-chemotherapy use occurred in age<75 vs ≥75 years (48% vs 6%, p=0.002), with 79%(n=22) receiving capecitabine. There was no significant difference in ECOG performance status(p=0.315), nor sites of metastases(p=0.695), between the 2L-chemotherapy vs 2L-fulvestrant groups. Median PFS on 2L-chemotherapy and 2L-fulvestrant was 5.49 and 3.91 months, respectively(p=0.178). Of the 58 (81%) patients who had progressed on 2L, 74%(n=43) had received 3L-therapy, of which 54%(n=31) received 3L-chemotherapy, and 12%(n=7) fulvestrant. Median PFS was significantly longer on 3L-chemotherapy versus 3L-fulvestrant (4.27 vs. 2.27 months, p=0.040).
Conclusion:
Treatment patterns beyond 1L CDK4/6i+ET are heterogeneous, with chemotherapy uptake higher in younger patients and later treatment lines. With small patient numbers, overall survival data remains immature and cannot yet inform clinical practice. Patient recruitment and follow-up continues.
Cyclin-dependent kinase inhibitor + endocrine therapy (CDK4/6i+ET) is standard first-line(1L) treatment for hormone receptor-positive advanced breast cancer (HR+/HER2-ABC). Treatments after 1L-progression vary, with limited trial data to inform treatment selection. This retrospective study evaluates patterns of second-line(2L) and beyond treatment in patients with HR+ABC.
Methods:
Data was retrieved from ARORA, a multi-centre Australian registry capturing patient, tumour, treatment and outcome information for patients with HR+/HER2-ABC. Patients who received 2L-treatment after failure of 1L CDK4/6i+ET were included. Univariate and multivariate analyses were conducted with SPSS. Correlation was assessed with Chi-square and Fisher’s exact testing, with Log-rank for survival analyses.
Results:
454 patients diagnosed with HR+/HER2-ABC from 1/1/2020-9/9/2024 were enrolled in ARORA, with 300 receiving 1L CDK4/6i+ET. 72(16%) patients who received 1L CDK4/6i+ET had experienced progression, and initiated 2L treatment at time of analysis and were included.
Median follow-up from ABC diagnosis was 39.2 months. Median age of 2L patients was 61.5 years(range 34-85). 39%(n=28) received 2L-chemotherapy and 26%(n=19) received 2L-fulvestrant. 35%(n=25) received other treatment, including 8%(n=6) CDK4/6i+fulvestrant, 3%(n=2) everolimus, 6%(n=4) AKT-inhibitor, 1%(n=1) PIK3CA-inhibitor and 1%(n=1) clinical trial. Greater 2L-chemotherapy use occurred in age<75 vs ≥75 years (48% vs 6%, p=0.002), with 79%(n=22) receiving capecitabine. There was no significant difference in ECOG performance status(p=0.315), nor sites of metastases(p=0.695), between the 2L-chemotherapy vs 2L-fulvestrant groups. Median PFS on 2L-chemotherapy and 2L-fulvestrant was 5.49 and 3.91 months, respectively(p=0.178). Of the 58 (81%) patients who had progressed on 2L, 74%(n=43) had received 3L-therapy, of which 54%(n=31) received 3L-chemotherapy, and 12%(n=7) fulvestrant. Median PFS was significantly longer on 3L-chemotherapy versus 3L-fulvestrant (4.27 vs. 2.27 months, p=0.040).
Conclusion:
Treatment patterns beyond 1L CDK4/6i+ET are heterogeneous, with chemotherapy uptake higher in younger patients and later treatment lines. With small patient numbers, overall survival data remains immature and cannot yet inform clinical practice. Patient recruitment and follow-up continues.
Biography
Carl is a physician trainee at Eastern Health with a strong interest in the clinical and research aspects of medical Oncology. He is currently studying a Master of Cancer Sciences at the University of Melbourne. He has a research interest in solid tumour oncology, particularly lung and breast malignancies. His recent work includes a publication exploring the molecular mechanisms driving small cell lung cancer metastasis. Carl's current project involves the ARORA breast cancer registry, where he has been working with his supervisors and WEHI, assessing treatment and survival in HR+/HER2- advanced breast cancer patients after failure of first-line CDK4/6-inhibitor+endocrine therapy.
Session Chair
Jessica Smith
Medical Oncologist
Macquarie University Hospital
