Taking a closer look at the EMERALD trial, Dr Bardia shares key efficacy outcomes from the sub-group analyses 1) of patients with no prior chemotherapy and 2) comparing elacestrant to fulvestrant or AI.
Dr. Aditya Bardia: EMERALD trial evaluated Elacestrant was a standard of care endocrine therapy aromatase inhibitor fulvestrant for patients with ER-positive HER2-negative metastatic breast cancer. The trial overall was positive, showed an improvement in progression-free survival in all comers. You could see a stronger signal in ESR1 mutant metastatic breast cancer. The trial did allow one prior line of chemotherapy so we saw subset analysis looking at patients who had not received prior chemotherapy. Essentially patients who had not received prior chemotherapy could see treatment with Elacestrant was associated with prolonged progression-free survival compared to standard-of-care endocrine therapy hazard ratio of 0.68. The median progression-free survival was 3.7 months with Elacestrant versus two months with standard-of-care endocrine therapy. If you look at landmark analysis, and that's important for EMERALD trial because if you look at the curves, you see an initial drop in the curves and then separation highlighting that median PFS might not be the best way to look at efficacy in the EMERALD trial. Landmark analyses like six months and 12 months PFS is a good metric. If you look at 12-month PFS, it was 27% with Elacestrant versus 12% with standard-of-care endocrine therapy. You could clearly see a separation in patients who have endocrine sensitive disease. This was particularly seen in patients with mutant ESR1 breast cancer. As I mentioned earlier, in tumors that have mutations in the estrogen receptor, the tumor is still ER-dependent so drugs that would directly bind to ER like Elacestrant would work in this setting. In patients with mutant ESR1 breast cancer, you could see improvement in progression-free [00:18:00] survival hazard ratio of 0.54 with Elacestrant median PFS 5.3 months versus 1.9 months with standard endocrine therapy. Finally, if you look at the landmark 12-month PFS analysis, it was 31% with Elacestrant so one in three patients being without disease progression at 12 months with Elacestrant versus 12% with standard endocrine therapy. Overall you could see that in patients who had not received prior chemotherapy, that was a prognostic factor and you could clearly see benefit with Elacestrant as compared to standard endocrine therapy.
The most common adverse events seen with Elacestrant was nausea in the EMERALD trial, which is not surprising because it's an oral pill. In general, patients do not need anti-nausea medications. The percentage of treatment discontinuation was quite low with Elacestrant. It's just something that's seen because it's an oral agent. Outside of nausea, the AEs are pretty much similar between Elacestrant and endocrine therapy in terms of arthralgia and hot flashes. A side effect that was not seen with Elacestrant was pain that's associated with intramuscular shot because it's an oral agent. That's something that we see with fulvestrant which is given as an intramuscular injection.
In subset analyses of the EMERALD trial, Elacestrant was compared to the individual endocrine therapy agents that were utilized, aromatase inhibitors as well as fulvestrant. This was presented at ESMO 2022 by Dr. Philippe Aftimos. Essentially benefit with Elacestrant was seen both against AI as well as against fulvestrant. Patients who received Elacestrant had prolonged PFS at six, 12, even 18 months as compared to fulvestrant both in the overall population as well as patients who had ESR1 mutations. For example, if we compare Elacestrant to fulvestrant, the six-month PFS rate in the ESR1 mutant subgroup was 40.8% as compared to 20.8% with the use of endocrine agents. Similarly, you could see an improvement at 12 months, 26.8% with Elacestrant versus 8.4% with the fulvestrant. You could clearly see benefits with Elacestrant as compared to fulvestrant in these landmark analyses.