ABSTRACT NUMBER – 1057
We have received a thorough explanation of SERDs. However, a selective estrogen receptor modulator (SERM) is also available that effectively targets ESR1 mutants. The only SERM currently approved for treating ESR1-mutated ER+/HER2- metastatic breast cancer in the second-line setting is lasofoxifene. Lasofoxifene is being investigated as a potent and bioavailable selective estrogen receptor modulator with a distinct safety profile that could be beneficial for postmenopausal women and premenopausal women with ovarian suppression dealing with locally advanced or metastatic ER+ breast cancer. According to data presented at ASCO 2023, as of April 2023, out of the 29 patients enrolled, 6 were still undergoing treatment, 17 experienced disease progression, and 1 had discontinued due to adverse events (AEs).
Regarding safety findings, the combination of lasofoxifene and abemaciclib was generally well tolerated, with mostly grade 1/2 treatment-emergent adverse events (TRAEs) observed, including diarrhea, nausea, fatigue, and vomiting. Additionally, there were grade 3 and higher TRAEs reported, such as anemia (10.3%), hypokalemia (10.3%), falls (6.9%), and others. Notably, there were no deaths recorded during the treatment period, which is a promising outcome.
In terms of efficacy, the lasofoxifene/abemaciclib combination demonstrated a clinically significant median progression-free survival (PFS) of 13 months, along with a clinical benefit rate (CBR) of 65.5% and an objective response rate (ORR) of 55.6%. The median overall survival could not be estimated during the study. Furthermore, the PFS rates at 6, 12, and 18 months were 76.1%, 56.1%, and 38.8%, respectively. This combination of lasofoxifene and abemaciclib exhibited strong therapeutic activity by overcoming endocrine resistance-associated alterations.
