REAL WORLD ELACESTRANT

In this video, Prof Dr François Duhoux and Dr Maxwell Lloyd discuss the data of a Real World Study with elacestrant that was presented during Poster Spotlight Session 7 at SABCS 2024  on targeting the ER and PI3K pathway with novel drugs and combinations.

Elacestrant, the first and currently only approved oral selective estrogen receptor degrader (SERD), has been integrated into routine clinical practice for patients with ESR1-mutated, hormone receptor-positive metastatic breast cancer following the positive results of the EMERALD trial. A real-world analysis was conducted using the GuardantINFORM database, which combines clinical and genomic data from circulating tumour DNA sequencing and treatment claims records. This analysis included 756 patients with ESR1-mutated advanced breast cancer who had started elacestrant therapy within six months of detecting the mutation.

The real-world cohort tended to be more heavily pretreated than the population in the EMERALD trial. While all patients had prior endocrine therapy, a majority had received CDK4/6 inhibitors, over 40% had undergone one or more lines of chemotherapy, and most received elacestrant as a fourth-line or later option. A trend was observed toward earlier use in second or third-line settings as the drug gained acceptance in clinical practice.

Key outcomes assessed were time-to-next treatment (a surrogate for progression-free survival) and time-to-treatment discontinuation. The median time-to-next treatment was 6.4 months, and the median time-to-treatment discontinuation was 4.6 months in the overall cohort. Biomarker analysis revealed that patients with tumours harbouring PI3K pathway alterations (PIK3CA, AKT1, or PTEN mutations) had significantly worse outcomes, including shorter time-to-next treatment, shorter time-to-treatment discontinuation, and worse overall survival. Clinical factors, such as prior fulvestrant exposure, showed a trend toward worse outcomes, although this finding was not statistically significant.

These findings provide valuable insights into real-world elacestrant use, confirming its role in heavily pretreated populations while highlighting the impact of genomic alterations and prior therapies on treatment outcomes. Future analyses may further refine the optimal placement of elacestrant in the treatment sequence for metastatic breast cancer.