Dr Tarantino on the Expansion of Treatment Options Post-CDK4/6 Inhibition in HR+ Breast Cancer

Paolo Tarantino, MD, researcher, the European Institute of Oncology, clinical research fellow, Dana-Farber Cancer Institute, discusses the expansion and selection of effective treatment options for patients with hormone receptor–positive breast cancer who progressed on a CDK4/6 inhibitor.

The increasing number of available agents in the post-CDK4/6 inhibitor armamentarium continues to benefit patients with HR-positive breast cancer but does complicate the navigation of current therapeutics, Tarantino begins.

Prior to the approval of the oral selective estrogen receptor degrader (SERD) elacestrant (Orserdu), decision-making in the post-CDK4/6 inhibitor setting was often based on the presence or absence of PIK3CA mutations, Tarantino says. Patients with PIK3CA-mutated tumors were typically treated with alpelisib (Piqray) plus fulvestrant (Faslodex), while those without PIK3CA mutations were given either fulvestrant monotherapy or a different CDK4/6 inhibitor, Tarantinostates. The mTOR inhibitor everolimus (Afinitor) is also an approved subsequent line of therapy in this space, Tarantino adds.

Elacestrant was the first oral SERD granted approval for the treatment of adults with HR-positive, HER2-negative, ESR1-mutated advanced or metastatic breast cancer who progressed on one or more prior lines of endocrine therapy in January 2023, Tarantino reports. The approval was supported by findings from the phase 3 EMERALD trial (NCT03778931).

Unlike PIK3CA mutations, ESR1 mutations are rarely present in the primary tumor. Instead, this mutation commonly arises during endocrine treatment, especially with an aromatase inhibitor, Tarantino explains. Therefore, it has become increasingly vital to test for this mutation after progression on a CDK4/6 inhibitor using liquid biopsy, he states. This information is often considered alongside the patient's time on a prior CDK4/6 inhibitor, which serves as a surrogate measure for endocrine sensitivity, Tarantino says. Patients who harboran ESR1 mutation and received at least 1 year of prior CDK4/6 inhibition may benefit from elacestrant, Tarantino concludes.