AMEERA-1: Phase 1-2 Study of Amcenestrant, An Oral Selective Estrogen Receptor Degrader, With Palbociclib in Postmenopausal Women With ER+ HER2- Metastatic Breast Cancer - Episode 2

ER+/HER2- Metastatic Breast Cancer and Available Treatment Options

A medical oncologist discusses the available treatment options for ER+/HER2- metastatic breast cancer.

Sarat Chandarlapaty, MD: For advanced breast cancer, there are a couple of treatment modalities. The mainstay of treatment is systemic therapy, drug therapy that goes to all locations where metastatic disease may be located. There are 2 classes of therapy. There are what we call endocrine therapies and chemotherapies. By endocrine therapies, we’re referring to antiestrogens as a backbone often given in combination with additional targeted therapies. Those targeted therapies are CDK4/6 inhibitors or drugs targeting the PI3 kinase pathway: a PI3 kinase inhibitor or an mTOR inhibitor.

Most of these endocrine therapies have been developed to where they’re given together with those targeted therapies. The endocrine therapies can also be given as single-agent antiestrogens. That grouping of therapies, hormone therapies, and antiestrogens together with targeted agents or as single-agent hormone therapies. The other big class, of course, is chemotherapies that we’re very familiar with and drugs that are used for many types of cancers. In large measure, these are reserved for after failure of the endocrine-targeted therapies.

Historically it’s been a challenge to decide which systemic therapies to give when you have this menu of options. Endocrine therapies were given for patients with more limited symptomatic disease and chemotherapies were given up front for patients for patients who had visceral disease, liver metastases, or symptomatic disease where you needed a very fast response. That dichotomy still exists to some degree, but it’s largely been replaced by the combination of hormone therapies that, together with CDK4/6 inhibitors, work as effective as chemotherapies in inducing responses and alleviating symptoms of disease.

Based on overall survival data as well as that efficacy, the first treatment of choice is largely a hormone plus CDK4/6 inhibitor combination. Subsequent to that, patients may go on to chemotherapy or another targeted regimen. That choice is guided by clinical intuition of whether the endocrine therapy was somewhat effective or if it was completely ineffective. Often there’s a consideration for going next to chemotherapy.

Transcript edited for clarity.