First- and second-line treatment strategies for hormone-receptor (HR)-positive HER2-negative metastatic breast cancer: A real-world study

Background Endocrine therapy (ET) plus cyclin-dependent-kinases 4/6 inhibitors (CDK4/6i) represents the standard treatment for luminal-metastatic breast cancer (MBC). However, prospective head-to-head comparisons are still lacking for 1st line (L) options, and it is still crucial to define the best strategy between 1st and 2nd L. Materials and methods 717 consecutive luminal-MBC pts treated between 2008 and 2020 were analyzed at the Oncology Department of Aviano and Udine, Italy. Differences about survival outcomes (OS, PFS and PPS) were tested by log-rank test. The attrition rate (AR) between 1st and 2ndL was calculated. Results At 1 st L, pts were treated with ET (49%), chemotherapy (CT) (31%) and ET-CDKi (20%) while, at 2 nd L, 33% received ET, 33% CT and 8% ET-CDKi. Overall AR was 10%, 7% for CT, 8% for ET and 17% for ET-CDKi. By multivariate analysis, 1 st L ET-CDK4/6i showed a better mPFS1 and OS. Moreover, 2 nd L ET-CDK4/6i demonstrated better mPFS2 compared to ET and CT. Notably, 1 st L ET-CDKi resulted in higher mPFS than 2ndL ET-CDKi. Intriguingly, 1 st L ET-CDK4/6i was associated with worse mPPS compared to CT and ET. Secondarily, 1 st L ET-CDK4/6i followed by CT had worse OS compared to 1 st L ET-CDK4/6i followed by ET. Notably, none of baseline characteristics at 2 nd L influenced 2 nd L treatment choice (ET vs. CT) after ET-CDKi. Conclusion Our real-world data demonstrated that ET-CDKi represents the best option for 1 st L luminal-MBC compared to ET and CT. Also, the present study pointed out that 2 nd L ET, potentially combined with other molecules, could be a feasible option after CDK4/6i failure, postponing CT on later lines.