Elacestrant improves outcomes for ER+ metastatic breast cancer

Background

Endocrine (or hormone) therapy plus CDK 4/6 inhibitors is the standard first treatment for ER+/HER2- metastatic disease. The endocrine therapy often takes the form of fulvestrant. In most people, the medicines ultimately fail to stop cancer from progressing. The cancer becomes resistant to treatment, sometimes due to a change in the ESR1 gene. This gene is increasingly being looked at as a marker for how people respond to treatment.

Fulvestrant was approved nearly 20 years ago. While no other drug has shown better results, fulvestrant used on its own does a poor job in keeping cancer from growing or spreading. For this reason, finding better endocrine therapies for metastatic breast cancer is a high priority.

Results

The phase III study randomized 477 men and postmenopausal women to two groups of similar size. The average age of participants was 63. All were ER+ and negative for HER2. Their cancers had progressed or relapsed on or after one or two lines of endocrine therapy, one with a CDK 4/6 inhibitor. Some participants had received one line of chemotherapy as well.

The study group received elacestrant. Doctors chose between fulvestrant or one of three aromatase inhibitors as the endocrine therapy for the control group. Most chose fulvestrant. The study looked at disease progression and overall survival.

The results were positive. Elacestrant resulted in a 30 percent reduction in disease progression or death compared to the control group. People whose cancers test positive for ESR1 saw an even greater reduction (45 percent). Progression-free survival was higher at both 6 and 12 months, as compared to the overall control group and to the subgroup of the control group taking fulvestrant.

The benefit was seen in participants older and younger than 65, in multiple races, across study sites in 17 countries. It was even seen in people who had been treated previously with fulvestrant, suggesting a more powerful endocrine therapy may still be effective with this group even after fulvestrant stops working.

Nausea was the main side effect, reported at higher rates than typical with endocrine therapy. Around 35 percent of participants taking the drug experienced nausea. Details on the severity of the nausea was not available. Other common side effects included fatigue and hot flashes, similar to other endocrine therapies.

There were no safety concerns with elacestrant. Participants who dropped out of the trial did so because of disease progression, not side effects.

What it means for people with ER+ metastatic breast cancer

Elacestrant is the first oral SERD to show improvement over the standard treatment. This is exciting news for people with ER+/HER2- metastatic breast cancer whose cancers do not respond to fulvestrant or aromatase inhibitors. Cancers that test positive for ESR1+ may be even more likely to benefit from the drug.

These results are preliminary, and it’s worth noting that this drug is not yet approved by the U.S. Food and Drug Administration. The final analyses will come out in late 2022 or early 2023. This study only included postmenopausal women and men because there was no safety information on premenopausal women. Future studies may include younger women.

Initial results suggest that the drug may cause nausea at a higher rate than other endocrine therapies. More information on the severity of nausea may be available in the future. In addition, the cost of elacestrant is not yet known. It will likely be higher than fulvestrant, which is available in generic form.