AMEERA-5: A Randomized, Double-Blind Phase III Study of Amcenestrant + Palbociclib vs Letrozole + Palbociclib for Previously Untreated ER+/HER2- Advanced Breast Cancer - Episode 4

AMEERA-5: Key Data and Implications for Practice

An expert in breast oncology shares her thoughts on the importance of the AMEERA-5 findings to the evolving treatment landscape for HR+ breast cancer.

Sara Hurvitz, MD: The AMEERA-5 clinical trial is an ongoing prospective, multinational, randomized, double-blind, double placebo-controlled clinical trial , which is phase 3, that is comparing the efficacy and safety of the amcenestrant plus palbociclib compared to letrozole plus palbociclib in patients who have advanced or locally recurrent unresectable metastatic breast cancer that’s ER positive [estrogen receptor]- and HER2 [human epidermal growth factor receptor 2] -negative. The study is enrolling patients who have not received prior therapy for metastatic disease. Patients who are excluded include those who’ve received another SERD [selective estrogen receptor down-regulator] for the treatment of early-stage disease or disease recurrence on or within 12 months of completion of adjuvant endocrine therapy. Patients who are eligible are randomly assigned 1:1 to each of the treatment arms, and the treatment cycles are 28 days each. The stratification criteria for randomization include de novo metastatic disease, yes or no, menopausal status, pre or postmenopausal, as well as visceral metastases.

The planned enrollment for this clinical trial is nearly 1100 patients. This study is going to be open widely internationally at over 350 sites in over 30 countries. It’s a large study with ongoing accrual occurring now. The endpoints. The primary endpoint is progression-free survival. The secondary end point is overall survival. And there are a number of other more exploratory endpoints including objective response rate, duration of response, clinical benefit rate, quality of life metrics, pharmacokinetics, safety, time to chemotherapy, and [progression-free survival].

If AMEERA-5 shows a clinically meaningful and significant improvement in progression-free survival associated with amcenestrant compared to letrozole in the frontline setting, it may end up becoming a new standard of care for the frontline treatment of ER-positive advanced breast cancer. These data would be exciting because it would provide rationale for the use of an oral SERD. Currently we only have an IM SERD [intramuscular selective estrogen receptor down-regulator] available to use in patients with ER-positive metastatic disease. If these results are promising as well, it would pave the way for other clinical trials potentially in earlier line settings, such as the adjuvant clinical trial setting, and/or in combination with other targeted therapies, including other CDK4/6 [cyclin-dependent kinases 4 and 6] inhibitors, potentially PI3 kinase pathway inhibitors among others.

Transcript edited for clarity.