The Evolving World of Oral SERDs: A Deep Dive into Patient Selection, Sequencing Strategies, and Emerging Data - Episode 4
Expert Insights on Patient Selection and Sequencing Strategies in HR+/HER2– mBC
A panelist discusses how elacestrant should be used as soon as ESR1 mutations emerge, emphasizing that it works equally well in visceral and bone metastases and that ESR1 mutations must be targeted before other mutations due to their resistance-driving nature.
Treatment Selection and Mutation Priority
Elacestrant should be initiated immediately upon detecting ESR1 mutations, regardless of whether patients are transitioning from first-line aromatase inhibitor plus CDK4/6 inhibitor combinations or have fulvestrant-refractory disease. The drug’s efficacy appears independent of ESR1 mutation status when used in appropriate clinical contexts. Treatment decisions should prioritize the primary resistance pathway over secondary mutations.
When patients harbor multiple mutations, such as ESR1 alongside PIK3CA mutations, effective estrogen receptor pathway blockade takes priority. The oncologist uses an analogy of cancer having “front and back doors”—blocking the secondary pathway (back door) while leaving the primary ESR1-mediated pathway (front door) inadequately blocked allows continued tumor growth. Elacestrant provides comprehensive ESR1 pathway inhibition, making it the logical first choice.
Clinical factors like visceral versus bone metastases, number of metastatic sites, and variant allele frequencies don’t significantly impact elacestrant’s efficacy. The drug works equally well in patients with liver or lung metastases compared to bone-only disease, and effectiveness doesn’t vary by metastatic disease burden. Duration of response to prior endocrine therapy serves as the best predictor of elacestrant benefit, with patients responding for 12-plus months being ideal candidates.
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