224P Efficacy of single-agent second-line fulvestrant (FUL) in metastatic invasive lobular carcinoma (mILC) exposed to first-line aromatase inhibitors (AI) and cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6is)

Endocrine therapy (ET)-sensitive mILC responds well to first-line AI in combination with CDK4/6is. Recent studies have assessed the efficacy of single agent oral selective estrogen receptor degrader (SERD) in comparison to FUL post exposure to AI plus CDK4/6is revealing markedly reduced median progression-free survival (mPFS) in the FUL arm of approximately 2 months. This showcases an area of unmet need for patients post exposure to AI plus CDK4/6is. The impact of histology was not examined and could have important clinical implications. Establishing a historical control dataset for single-agent FUL can be hypothesis generating, offering valuable insights that may inform the design of future ILC-specific studies. In an observational, single-institution investigation using data from the MD Anderson breast cancer prospectively collected electronic database, we searched for patients with a diagnosis of HR+ HER2-negative mILC who received second-line FUL following AI plus CDK4/6is. The method of Kaplan and Meier was used to estimate the distribution of overall survival (OS) and PFS. We reviewed 369 mILC patients, of whom 25 received single agent FUL and were included in the final analysis. Patient characteristics showed a median age of 60, 85% were non-Hispanic, 90% were White; all had ER positive tumors, 70% were PR positive, and 60% were HER2-low. 80% of the patients received prior palbociclib with 15% receiving ribociclib, and 5% receiving abemaciclib. The mPFS was 2.2 months with 95% confidence interval (CI) 1.8 – 4.5, and a 6-month PFS of 17.7%. The mOS was 10.4 months with 95% CI 7.5 – 15.4, and a 12-month OS of 44.3%. This is the only analysis to date to report outcomes of second-line single agent FUL in mILC patients exposed to AI plus CDK4/6is. Our findings underscore the urgent need for exploring novel therapeutic approaches and combinations in this patient population to improve outcomes in mILC. These results serve as an important historical controls for informing the design and development of future studies tailored specifically to address the unique challenges posed by mILC.