First- and second-line treatment strategies for hormone-receptor (HR)-positive HER2-negative metastatic breast cancer: A real-world study. (June 2021) - Basile, Debora
Abstract: 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. Highlights: To define the best treatment strategy for 1st and 2nd L is crucial for luminal mBC. 1st L CDK4/6i-based therapies represent the standard treatment in luminal mBC. This study confirmed the key role of 1st L CDK4/6i on a real-world cohort. This study suggested a preeminent role for ET after first-line CDK4/6i. The 2nd line ET with other molecules could allow to further postpone CT.