Real-World Outcomes of Ribociclib and Aromatase Inhibitor Use in First Line Hormone Receptor Positive, HER2-Negative Metastatic Breast Cancer

KARMA, a registry of patients who received first-line treatment with ribociclib and aromatase inhibitor (AI) for hormone receptor positive, HER2 negative metastatic breast cancer, was designed to analyse real-world treatment and survival outcomes. This study demonstrated that ribociclib and AI in this real-world clinical setting were well tolerated with encouraging survival data when compared to MONALEESA-2, the landmark clinical trial. Background: International guidelines recommend combining a CDK4/6 inhibitor and endocrine therapy (ET) as first line treatment for hormone receptor (HR) positive, HER2 negative metastatic breast cancer (MBC). Results from MONALEESA-2 demonstrate superior progression free survival (PFS) and overall survival (OS) with ribociclib (CDK4/6 inhibitor) and ET compared to ET alone. Real world outcomes have yet to be reported. Materials and Methods: KARMA is a non-interventional registry of Australian patients receiving first-line treatment with ribociclib and aromatase inhibitor (AI), obtained via a Medicine Access Program (MAP) for HR+, HER2- MBC. Outcomes were compared with the ribociclib/letrozole cohort in MONALEESA-2. Results: Data from 160 patients at 17 sites was analysed. Median follow-up is 36.5 months. Compared to MONALEESA-2, patients were numerically younger (54.3 vs. 62 years), with higher rates of bone-only metastases (31% vs. 21%). A total of 63 of 160 (39%) patients remain on treatment. A total of 56% of patients had at least 1 dose reduction, with neutropenia (68%) and abnormal liver enzymes (17%) the most common reasons. A total of 17 of 160 (11%) discontinued treatment due to toxicity, with no treatment related deaths. Median PFS was not reached (95% CI 29.9- NR), with PFS at 12 months and 18 months being 76% and 67% respectively versus 25.3 months, 73% and 63% in MONALEESA-2. Conclusion: The ribociclib and AI combination was well tolerated in this real-world setting. The KARMA registry cohort achieved a superior PFS ( >36.5 months) to MONALEESA-2, potentially due to more favourable baseline disease characteristics. Less frequent assessment scheduling in this non trial setting may also contribute.