Selective Estrogen Receptor Degraders Show Promise in Breast Cancer

Results from two clinical trials highlighted how new selective estrogen receptor degraders (SERDs) are showing promise in the treatment of breast cancer.

Data from the phase II SERENA-2 trial offered evidence that camizestrant improved progression-free survival (PFS) compared with fulvestrant among patients with estrogen receptor-positive, HER2-negative breast cancer, and an update from the phase III EMERALD trial showed that elacestrant remains superior to standard-of-care therapy for hormone receptor-positive metastatic breast cancer with longer duration of a prior CDK4/6 inhibitor. Both studies were presented at the San Antonio Breast Cancer Symposium.

In this exclusive MedPage Today video, EMERALD’s lead author François-Clément Bidard, MD, PhD, of the Institut Curie in Paris, discusses the findings of both trials.

Following is a transcript of his remarks:

At San Antonio, we had a session mostly dedicated to HR-positive, HER2-negative metastatic breast cancer, and most especially focused on second line of therapy. So first we had an abstract, a report on the EMERALD trial. EMERALD was a phase III trial, a registrational global trial with elacestrant, which is a new oral SERD. And they have shown previously that elacestrant was better than single-agent endocrine therapy in patients who progressed on first-line CDK 4/6 inhibitor plus elacestrant.

So that trial was reported as positive last year at San Antonio, and this year they reported a new subgroup analysis. And what was the most interesting is that not only did it confirm superiority of elacestrant versus single-agent endocrine therapy in the context of the second line, but that superiority is modulated by the time spent on prior CDK 4/6 inhibitor. So the time spent on the first line has a strong impact on the PFS that is achieved by elacestrant in the second line. So the longer the patient stays on the CDK 4/6 in first line, the longer the benefit of elacestrant was reported.

And the PFS of the standard arm was quite stable over time. So it did not fully impact the PFS in the standard arm, but it has a good impact on the elacestrant PFS. So that was the main take-home message for the EMERALD abstract.

We also had a study, a phase II study, which was testing another SERD, camizestrant. And that study was SERENA-2. It’s a phase II study, so that study is not registrational, it is exploratory. And in this study they compared two different doses of camizestrant — so two arms with different doses of camizestrant and a third arm with fulvestrant.

So the main take-home message here is camizestrant is more active than fulvestrant, and subgroup analysis showed that this activity is mostly observed in ESR1-mutated patients. Which means that, same as in EMERALD, the new generation, this next generation of oral SERDs are apparently more efficient in the second line when given to patients who have a detectable ESR1 mutation in their blood.

Another interesting finding is, whatever the subgroups they looked at, camizestrant was superior to fulvestrant in patients with adverse prognostic factors. So patients with liver or lung metastases benefited more from camizestrant than fulvestrant. It was the same for patients being exposed to prior AI [aromatase inhibitor] versus no prior AI. So each time they looked at the patient subgroup, patients with the adverse prognostic factor were the patients benefiting the most from camizestrant versus fulvestrant.

So take-home message is camizestrant is working, it’s better than fulvestrant, and its activity is mostly seen in ESR1-mutated patients. So that is very promising for ongoing phase III studies with camizestrant … that is specifically targeting ESR1 mutations that are appearing during the first line.