At the 2022 San Antonio Breast Cancer Symposium, Virgina Kaklamani, MD, MD Anderson Cancer Center, Houston, Texas, presented results of the EMERALD trial, investigating the impact of the duration of CDK4/6 inhibitor treatment on the efficacy of elacestrant for patients with metastatic ER-positive, HER2-negative breast cancer.

Dr Kaklamani also noted that elacestrant is currently under consideration by the Food and Drug Administration for approval as a monotherapy for this patient population.

Transcript

Hello, my name is Virginia Kaklamani. I'm a medical oncologist at UT Health San Antonio, MD Anderson Cancer Center. I'm co-director of the San Antonio Breast Cancer Symposium.

We are here at the 45th year of SABCS in San Antonio. Today, I presented the results of the EMERALD Trial. The EMERALD trial is a phase 3 clinical trial in patients with metastatic ER-positive, HER2-negative breast cancer that were randomized 1-to-1 to receive either elacestrant, which is an oral SERD [selective estrogen receptor downregulator], or standard-of-care endocrine therapy, which was either fulvestrant or an aromatase inhibitor, depending on what prior endocrine therapy they had received. Patients on the trial had to have received CDK-4/6 inhibitor treatment prior to entry to the trial, so 100% of the patients had been treated previously with a CDK-4/6 inhibitor.

The initial results of the trial, which were the primary end points, were presented last year at SABCS. They showed that elacestrant outperformed standard-of-care endocrine therapy in the whole patient population, as well as the patients who had tumors that were mutated for ESR-1 mutations.

This year, we tried to understand a little bit better what the patient population looked like, and if there was a patient population that might benefit more from endocrine therapy or less. We looked at tumors that we felt, based on how they had performed up until now, were endocrine-resistant, as well as some that were endocrine-sensitive.

We did an analysis based on the duration of a prior CDK-4/6 inhibitor treatment. We found that, even though elacestrant outperformed standard-of-care endocrine therapy in general and in ESR-1 mutated tumors, it seems that the longer the prior use of a CDK-4/6 inhibitor, the longer the progression-free survival (PFS) on EMERALD. If patients had been exposed to a CDK-4/6 inhibitor for less than 6 months, their PFS on EMERALD was less. Whereas the patients who had been exposed to a CDK-4/6 inhibitor for 18 months, their median PFS was longer.

That benefit in elacestrant compared to standard of care was more pronounced in patients that had mutated tumors for ESR-1 that had been on a CDK-4/6 inhibitor for more than 12 or more than 18 months. Their median PFS was around 8.6 months with elacestrant and around 2 months with standard-of-care endocrine therapy.

What does that mean for our patients? This means that elacestrant is currently being looked at by the FDA, and hopefully will receive approval in the next 2 months. This would be a good monotherapy option for the right patient.

Not every single metastatic breast cancer patient will be eligible for treatment with elacestrant. Ineligible patients will be those that clinicians feel still have endocrine sensitive disease. The way we define endocrine-sensitive, however, is going to be a little tricky. Sometimes we'll say, "How long were they on a CDK-4/6 inhibitor previously?" Sometimes we'll say, "These might be patients that have good characteristics of their tumors, and we feel that those tumors are endocrine-sensitive."

Monotherapy with elacestrant is going to be important because the toxicity profile is mild. This is a well-tolerated drug. It is definitely a better option than trying to give chemotherapy to our patients or potentially combination endocrine therapy.

Source:

Bardia A, Bidard FC, Neven P. “Overall survival results from EMERALD: A phase 3 trial evaluating elacestrant, an oral selective estrogen receptor degrader (SERD), vs investigator's choice of endocrine monotherapy for ER+/HER2- advanced breast cancer.” Presented at San Antonio Breast Cancer Symposium; December 6 – 10, 2022; San Antonio, Texas. Abstract GS3-01