Therapeutic impact of novel agents in patients with stage IV de novo HR+ve/Her2-ve breast cancer: Results from a real world dataset.

Abstract

1085 Background: The objective of this retrospective analysis was to look at the therapeutic impact of CDK4/6i and novel agents among pts with stage IV Denovo HR+ve/HER2-ve breast cancer (BC). Methods: We utilized a federated network of de-identified health data representing approximately 165 million pt lives available through the TriNetX Research Network. We identified 41,843 pts with HR+ve/HER2-ve stage IV Denovo BC treated diagnosed between Jan 2005 - Jan 2025. Propensity score matching analysis by age and site of metastases was carried out. OS was computed using the Kaplan Meier product limit method. The index event is the date of diagnosis. Results: 8,541(20.4%) received a CDK4/6i. Among pts treated with CDK4/6i 1,396(16.3%), 6,169 (72.2%) and 2,157 (25.2%) pts received Ribo, Palbo and Abema respectively. Over time there has been a significant decrease in use of palbocilcib with significant increase in use of abema and ribo. Median OS was similar between Ribo and Abema(HR 0.88; 95%CI (0.75,1.04) p=0.14). Compared to pts receiving palbo median OS was signficantly better among pts receiving abema (HR 0.77; 95%CI (0.69,0.85) p<0.0001) or ribociclib (HR 0.69; 95%CI (0.60,0.81) p<0.0001).628 pts received more than one CDK4/6i. (152 palbo + ribo, 118 ribo + abema, 368 abema+ palbo). 5-year OS was 63.9% and 70.4%(HR 1.37; 95%CI 1.06,1.77) respectively among pts who received 1 vs >1 CDK4/6i. Among patients treated with CDK4/6i, OS was significantly longer among pts who received elacestrant vs those who did not (HR 0.401; 95%CI (0.215,0.745). 228 pts treated with a CDK4/6i received an antibody drug conjugate (ADC). Median time to use of an ADC was 45m. 5yr OS was 75.8% vs 58.7% among those who did and did not receive an ADC respectively (HR 0.45, 95%0.30,0.67). 5yr OS was 76.2% vs 52.7% among those who did and did not receive Trastuzumab deruxtecan respectively (HR 0.37, 95%0.19,0.70). 5yr OS was 76.2% vs 60.4% among those who did and did not receive Sacituzumab govetican respectively (HR 0.40, 95%0.25,0.65). Conclusions: Among pts with stage IV Denovo HR+ve/HER2-ve BC treated with a CDK4/6i using a CDK4/6i beyond progression is an option. Novel agents such as oral SERDS and ADCs are also associated with improved prognostic outcome in the real world setting.