Breast cancer is the most common cancer in women. Hormone therapy is the major treatment option for patients with estrogen receptor-positive (ER+) and Her2-negative (Her2-) breast cancer. ESR1 mutation is one of the resistance mechanism which will be developed after the long-term hormone therapy treatment. Selective estrogen receptor degrader (SERD) is the potential option for patients with ESR1-mutated breast cancer. SAR439859 is a new oral SERD drug. In a phase I/II study, 63 patients previously treated with hormone therapy were received SAR439859. The paired biopsies and plasma samples were collected for monitoring the protein, RNA, and cfDNA change. In the results of the paired biopsies analysis, the decreasing of ER/PR/Ki67 protein and ER-activated gene expression indicated the on-targeted activity of SAR439859. In the results of plasma analysis, the decrease or clearance in ESR1 mutation was observed, including ESR1 D538G and Y537S. The clinical benefits were shown in 40% (12/30) ESR1 wild-type patients and 32% (9/28) ESR1-mutated patients. The results indicated that SAR439859 is a potential oral SERD for ER+/Her2- breast cancer.
Annals of Oncology (2020) 31 (suppl_4): S351