Dr Gupta on Considerations for Frontline Treatment Selection in HR+/HER2-Negative Breast Cancer

"There are a few different factors that I think about. The first is whether this is relapsed disease or de novo metastatic disease. In particular, if this is relapsed disease, I think about whether the patient was on adjuvant endocrine therapy at the time of relapse, or whether there had been a sizable interval since the patient completed adjuvant endocrine therapy and then had this relapse."

Tanya Gupta, MD, an oncologist at the Palo Alto Medical Foundation, discussed key considerations for the selection of frontline regimens for patients with metastatic hormone receptor (HR)–positive, HER2-negative breast cancer.

When selecting frontline treatment for patients with metastatic HR-positive, HER2-negative breast cancer, multiple clinical factors must be considered to optimize outcomes, Gupta began. The first distinction is whether the disease is relapsed or de novo metastatic, she stated. In cases of de novo metastatic disease, the standard first-line approach outside of a clinical trial is the use of a CDK4/6 inhibitor combined with an aromatase inhibitor, she detailed. For premenopausal patients, ovarian suppression should also be included, Gupta noted.

For relapsed disease, treatment selection depends on prior adjuvant endocrine therapy exposure, Gupta continued. If a patient relapses during adjuvant endocrine therapy but still appears to have endocrine-sensitive disease, the preferred regimen is a CDK4/6 inhibitor plus fulvestrant (Faslodex), she said. However, in cases where there is an early relapse after completing adjuvant therapy, concern for endocrine resistance arises, requiring a modified approach, Gupta explained. For patients with endocrine-resistant, PIK3CA-mutated disease, inavolisib (Itovebi) plus palbociclib (Ibrance) and fulvestrant is a preferred regimen based on findings from the phase 3 INAVO120 trial (NCT04191499), she reported.

Beyond endocrine sensitivity, disease burden and clinical presentation also influence treatment decisions, Gupta noted. Although rare, some patients present with visceral crisis, characterized by a high disease burden with organ dysfunction, she said. In such cases, chemotherapy-based regimens are preferred due to the need for a rapid response to stabilize the patient, Gupta concluded.