Is there any role for elacestrant in patient who have received prior fulvestrant if they have ESR1 mutation?

The short answer is Yes!!

The pivotal EMERALD trial that led to the approval of Elacestrant (oral Selective Estrogen Receptor Degrader) did enroll patients who previously received Fulvestrant (Faslodex).

In a pre-planned subgroup analysis of EMERALD data, benefit of Elacestrant was seen even in subgroup of patients who received prior Fulvestrant, with HR for PFS being 0.67 for that subgroup. There were 145 such patients out of total of 477 patients in the trial.

The reasoning for such a benefit seen with Elacestrant (oral SERD) in patients who progressed on Fulvestrant (I.M. SERD) lies in Elacestrant's superior bioavailability and greater ability to bind to mutated ESR1, leading to more effective ER Inhibition.

ESR1 Ligand binding domain mu...

The phase III EMERALD trial represented an important paradigm shift for HR+ metastatic breast cancer management (Bidard et al., PMID 35584336). This randomized prospective open-label study enrolled patients with advanced/metastatic HR+/HER2- breast cancer with prior progression on 1-2 endocrine therapies, which must have included a CDK4/6 inhibitor. Patients were allowed to have had up to one prior line of chemotherapy in the metastatic setting. Participants were randomized to treatment with a next-generation oral selective estrogen receptor degrader (SERD), elacestrant (n=239), or endocrine monotherapy as standard of care (n=238). ESR1 mutations were identified in 47.8% of patients. In the overall study population, 6-month progression-free...

As pointed out by the other experts, the EMERALD Trial did enroll patients with ESR1 mutation positive HR+/HER2- breast cancer who previously received fulvestrant, and such patients appeared to derive similar benefit from elacestrant as patients who were not previously treated with fulvestrant as noted on the forest plot figure in the study publication (although 95% CI did cross 1.0, likely due to smaller numbers of patients). Given this, I would feel comfortable offering elacestrant to patients with metastatic ESR1 mutation positive, HR+/HER2- breast cancer, and progression of disease on fulvestrant.