Abstract PS2-02-29: Real world evidence of systemic therapy in hormone receptor positive advanced breast cancer (HR+ ABC) in Australia - ARORA Registry

Abstract

BACKGROUND: The incorporation of cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) into first line (1L) systemic treatment for patients with HR+ ABC is now standard practice and leads to improved survival. However, there is a paucity of data on uptake of standard therapies and their associated toxicities in the real-world setting. Here, we present updated results from the ARORA registry.

METHODS: ARORA is a secondary data use study of Australian patients aged ≥18 years and diagnosed with HR+ ABC after 1 Jan 2020. Prospective data is captured on patient characteristics, disease course, systemic therapy sequencing and treatment outcomes in routine clinical practice. Database lock for analysis was 19 May 2025.

RESULTS: Data was analysed from 457 patients at 17 sites, with a median follow-up of 38.8 months. Median age was 64 years (24% ≥75 years). 65.6% were ECOG 0-1 and 2.8% had a BRCA1/2 pathogenic variant. 44.2% had liver or lung metastases, and 19% had bone-only disease. 60.4% had relapsed metastatic disease. Of these, 9.1% and 46.7% had received neoadjuvant and adjuvant chemotherapy respectively following early stage disease, and 75.2% had received adjuvant endocrine therapy (ET). 44.5% relapsed within 12 months of stopping adjuvant ET. 9 patients (2%) did not receive any systemic therapy for ABC. Of the 448 patients on 1L therapy, 335 (74.8%) received CDK4/6i + ET, 67 (15%) received ET alone and 41 (9.1%) received chemotherapy. Clinician preference for 1L CDK4/6i was palbociclib (32.6%), followed by ribociclib (27.2%) and abemaciclib (11.2%). Patients who received 1L ET alone were older (median 79 vs 63 years, 62.7% vs 18.5% ≥75 years), with poorer performance status (44.8% vs 8.7% ECOG ≥2) and more co-morbidities (29.8% vs 10.5% Charlson index ≥2). Conversely, those who received 1L chemotherapy were younger (median 58 years, 7.3% ≥75 years), with better performance status (46.3% vs 37.9% ECOG 0) and fewer co-morbidities (92.7% vs 88.9% Charlson index <2). They were more likely to have visceral metastases compared to those on CDK4/6i + ET (58.5% vs 45.7%), particularly liver metastases (46.3% vs 19.1%). Median 1L progression-free survival with 1L CDK4/6i + ET was 33.9 months, consistent with the upper end reported in trials (23.8–33.6 months). Common reported toxicities with CDK4/6i were diarrhoea (62.2% abemaciclib vs 10% ribociclib vs 6.6% palbociclib), neutropenia (44.9% palbociclib vs 40.8% ribociclib vs 22.2% abemaciclib) and nausea/vomiting (28.3% ribociclib vs 22.2% abemaciclib vs 17.6% palbociclib). Hepatotoxicity occurred in 5.8% ribociclib vs 4.6% abemaciclib vs 0.7% palbociclib. 2.5% of patients on ribociclib had QTc prolongation. Pneumonitis occurred in 1 patient on each CDK4/6i. Treatment was stopped due to toxicity for 20.5% ribociclib, 18% abemaciclib and 12.3% palbociclib. At the time of database lock, 117 of 335 patients (34.9%) who received 1L CDK4/6i + ET had moved to second line (2L). 60 (51.3%) received chemotherapy alone, 39 (33.3%) received ET alone and 5 (4.3%) received targeted therapies (e.g. mTOR or PIK3CA inhibitors). Capecitabine was the most common chemotherapy regimen (44/60, 73.3%). Median 2L duration of treatment was longest with targeted therapies (6.8 months), followed by chemotherapy (4.8 months) and ET alone (3.3 months). Overall survival data is immature.

CONCLUSION: While CDK4/6i + ET is recommended as 1L treatment of HR+ ABC, three-quarters of routinely treated patients received this combination. A substantial minority received ET alone or chemotherapy. Age, ECOG, co-morbidity burden and presence of visceral disease remain major determinants of treatment choice. CDK4/6i toxicity profiles are consistent with trials. In 2L, chemotherapy is preferred in over half of patients, but clinical outcomes trend better if targeted therapies are available.

Citation Format: M. Li, V. Wong, S. Baron-Hay, R. de Boer, F. Boyle, A. Campbell, I. M. Collins, K. Cuff, L. Gately, C. Georgiou, S. Greenberg, E. Jude, B. Karki, K. Mok, C. Morton, L. Nott, M. Nottage, N. Rainey, J. Torres, I. Tung, P. Gibbs, S. Lok. Real world evidence of systemic therapy in hormone receptor positive advanced breast cancer (HR+ ABC) in Australia - ARORA Registry [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS2-02-29.