Joyce A. O’Shaughnessy, MD: We’ve already talked a lot about the [phase 3] EMERALD [trial] data [NCT03778931]. I’m just going to just say a few words about the oral SERD [selective estrogen receptor degrader] elacestrant being approved by the FDA, just this year now is that we’ve heard that is being put into combination. We don’t have combination data yet, so I think it’s premature to put elacestrant together. You guys can correct me if I’m wrong here in a minute, but I’m cautious about putting it together until we have safety data in combination. But in the EMERALD trial now, everyone has metastatic HR+/HER2– [and] had to have had a prior CDK4/6 inhibitor. They could have had up to 1 line of chemotherapy, but a minority did. They could have had up to 2 lines of endocrine therapy. And it was a dual primary end point; it was progression-free survival [PFS] in the overall population regardless of ESR1 mutation status. And a group of patients, about 50% of the patients, had an ESR1 mutation ascertained on ctDNA [circulating tumor DNA] evaluation post progression on CDK4/6 and elacestrant is 400 mg once daily orally best given with food to decrease nausea. And, thankfully, proton pump inhibitors are OK; there’s no drug interaction. It doesn’t have to have an acidic environment to get absorbed. And then the control arm was investigator’s choice of an AI [aromatase inhibitor] or fulvestrant. And these are the patients in the population. About 70% had visceral metastasis. It was a pretty heavily burdened patient population because they had all progressed on a CDK4/6 inhibitor. And a minority had an inhibitor of the PI3 kinase pathway. Most of them had had 1 prior endocrine therapy in the metastatic setting with their CDK4/6 inhibitor. But about a third or so had 2 prior lines of endocrine; about 20% had had prior chemotherapy. And here you see up at the top, the median progression-free survival in all patients. We’re looking here at the 6-month and 12-month landmark analysis. And, you see, particularly if you go out to the 12-month median PFS, 9.4% of patients [were] progression-free with endocrine therapy alone—going up to 22% with a hazard [ratio] there of 0.7, which was statistically significant. Then in the ESR1 mutation disease only, which is the subset, and now this is the group that [the] FDA approved, is in about the 50% of patients that had an ESR1 mutation. The median PFS with the endocrine therapy alone was 1.9 months. Most of it, the vast majority of it, was fulvestrant. It doubled up to 3.8 months with…elacestrant alone. And if you look at the 12-month PFS rate, it was 8% with endocrine therapy alone in this ESR1 mutation population with mainly fulvestrant alone, which more than tripled up to 26% of patients progression-free. And you see the hazard ratio there of 0.55. So the relative efficacy of the elacestrant was more, was greater in the ESR1 mutation population. And, as Komal has said, if you look at the patients who at least got a year on their antecedent CDK4/6 inhibitor, it was 8.6 months median progression-free survival with single-agent elacestrant versus 1.9 months with the endocrine therapy, which is mostly fulvestrant. So that’s the best number we have that I’m aware of…. As Komal said, 7 months is like we’re tapping out at 7.3, but now this was 8.6 months [for] those who had at least a year of their antecedent CDK4/6 inhibitor. Survival is trending in the right direction here. For example, down the bottom, the ESR1 mutation population, 73% of patients alive in a year versus 82%. Not significant yet, but we’ll watch that space. The main toxicity is nausea. It’s low grade; about 35% of patients had low-grade nausea [and] only 8% took an antiemetic. But leading to study patients who had to actually discontinue therapy was only 6%. Only 3% had a dose reduction. So it tells you it’s quite well tolerated, but you see the 35% top left there on nausea all grade, but little grade 3, 4. A little bit [of] vomiting, more about a doubling of some vomiting, again, low-grade there. And that was about it. Not much different on fatigue, a little bit more diarrhea. Really, it’s low-grade nausea that is helped with food, and some vomiting. So that’s why elacestrant was approved post CDK4/6 progression in this ESR1 mutation population.

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