Real world evidence of systemic therapy in hormone receptor positive advanced breast cancer (HR+ ABC) in Australia: ARORA Registry.

Abstract

Background: The last decade has seen a rapid increase in systemic treatment options for patients with HR+ ABC. The incorporation of CDK4/6 inhibitors in first line (1L) is now standard practice leading to improved survival. However, there is a paucity of data on uptake of standard therapies and associated toxicities in the real-world setting. Methods: ARORA is a secondary data use study of Australian patients with HR+ ABC capturing prospective data on patient characteristics, systemic therapy sequencing and treatment outcomes in routine clinical practice. Patients aged > 18 diagnosed after 1 Jan 2020 are eligible. Results: Data from 294 patients at 16 sites was analysed with a median follow up of 15 months. Mean age was 63 years; 23% > 75 years. 64% were ECOG 0, 5.4% had a familial syndrome, 61% had relapsed metastatic disease and 19.4% had bone only metastases at diagnosis. Of patients who relapsed, 14.6% and 52.8% received neoadjuvant and adjuvant chemotherapy respectively, and 77.5% received adjuvant endocrine therapy (ET). 41% relapsed on or within 12 months of stopping adjuvant ET. 5 patients (1.7%) did not receive any systemic therapy for ABC. Of those on 1L therapy, 223 (77%) received CDK4/6i + ET, 38 (13.1%) received ET alone and 26 (9%) received chemotherapy. Choice of 1L CDK4/6i was palbociclib (50.7%), ribociclib (34.5%) and abemaciclib (9.9%). Patients who received 1L ET alone were older (mean age 75 vs 62 years; 68.4 vs 16.6% > 75 years) with poorer performance status (34.2 vs 6.3% ECOG ≥2) and more comorbidities (76.3 vs 36.8% Charlson index > 2) compared to those who received 1L CDK4/6i + ET. Conversely, those on 1L chemotherapy were younger (mean age 54, 96.2% < 75years), with better performance status (69.2% ECOG 0-1) and fewer comorbidities (88.5% Charlson index < 2). Patients receiving 1L chemotherapy were more likely to have visceral metastases compared to those on CDK4/6i + ET (69.2 vs 43.1%, p = 0.01). The most common reported toxicities in patients receiving CDK4/6i were diarrhea (59% abemaciclib vs 3.9% ribociclib vs 2.7% palbociclib), neutropenia (38.1% palbociclib vs 32.5% ribociclib vs 22.7% abemaciclib) and nausea/vomiting (27.3% abemaciclib vs 22.1% ribociclib vs 12.4% palbociclib). Abnormal LFTs occurred in 9.1% of patients on abemaciclib (vs 3.9% ribociclib and < 1% palbociclib). 2 patients (1.8%) on palbociclib had pneumonitis whilst 1 (1.3%) on ribociclib had QTc prolongation. Survival data is immature. Conclusions: Despite CDK4/6i + ET being gold standard treatment in 1L HR+ ABC, only 3/4 of patients received this combination, with a substantial minority receiving ET alone or chemotherapy. Age, ECOG status, comorbidity burden and presence of visceral disease appear to be major determinants of treatment choice. Toxicity profile of the CDK4/6i agents were mostly in line with clinical trial results, although longer follow up is needed to confirm this.