EMBER-3 Trial: Imlunestrant Plus Abemaciclib Improves Survival in Advanced Breast Cancer

Komal Jhaveri, MD, FACP, breast oncologist and early drug development specialist at Memorial Sloan Kettering Cancer Center, discusses results from the EMBER-3 trial (NCT04975308). The study evaluated imlunestrant as a monotherapy and in combination with abemaciclib in patients with ER-positive, HER2-advanced breast cancer who had previously received endocrine therapy.

The EMBER-3 trial results will be presented at the San Antonio Breast Cancer Symposium 2024 between December 10 to December 13.

This transcript has been lightly edited.

Transcript

What were the overall endpoints discovered in the EMBER-3 trial?

For the first primary endpoint, imlunestrant statistically significantly improved investigator assessed PFS [progression-free survival] compared with standard of care endocrine therapy with median PFS of 5.5 months vs 3.8 months, with a hazard ratio of 0.62.

For the second endpoint, which is investigator assessed PFS for imlunestrant vs standard of care endocrine therapy. PFS difference did not read statistical significance, the hazard ratio is 0.87. It's notable, however, that majority of the patients without any ESR1 mutation did not have a difference in PFS, the hazard ratio here is 1.

For the third primary endpoint, imlunestrant plus abemaciclib, significantly improved investigator assessed PFS compared with imlunestrant alone. These were patients regardless of ESR1 mutation status and the PD [programmed cell death] and PFS here was 9.4 months vs 5.5 months. The hazard ratio is 0.57.

When we looked at the key subgroups, consistent benefits for monotherapy were seen regardless of prior visceral metastases, absence or presence, prior CDK4/6 inhibitor therapy, or ESR1 mutation status. Similarly, when we looked at for the combination vs imlunestrant, consistent benefits were seen across these subgroups. In fact, we specifically looked at whether there was benefit with or without ESR1 mutations, there was consistent benefit.

When we looked at key subgroups, such as prior CDK4/6 inhibitor pretreated patients, 65% of the patients had a CDK4/6 inhibitor before they were enrolled to the combination of imlunestrant and abemaciclib.

We also looked at another key subgroup, which is looking at PI3K pathway mutation status because both of these are important and have implications for our current clinical practice. When we looked at both of them, consistent benefit was seen with imlunestrant plus abemaciclib.

In patients with prior CDK4/6 pretreated patients, we did see that the median PFS is 9.1 months, which is consistent to the overall patient population. Again, hazard ratio was consistent there as well with overall patient population. When we looked at PI3K path mutation status, median PFS was 7.6 months vs 4.8 months, again, consistent with what we've seen in terms of hazard ratio with overall patient population.