Dr Wander on Limitations of First- and Later-Line Therapies in HR+ Breast Cancer

Seth Wander, MD, PhD, instructor, medicine, Harvard Medical School; medical oncologist, Massachusetts General Hospital, discusses the present limitations of first- and later-line therapy for patients with hormone receptor (HR)–positive metastatic breast cancer.

In recent years, significant progress has been made in the development of novel frontline therapies for patients with HR-positive metastatic breast cancer, Wanderbegins. The current standard of care often includes an aromatase inhibitor combined with a CDK4/6 inhibitor, such as ribociclib (Kisqali), a regimen that has generated astatistically significant improvement in overall survival in the first-line setting, he explains.

However, there are still limitations and areas for improvement in treatment, Wandernotes. He says that on one end of the spectrum, patients with more aggressive disease—particularly those who progress shortly after adjuvant anti-estrogen or CDK4/6 inhibitor therapy—represent a high-risk population that requires more effective treatmentstrategies. Recent data from the phase 2/3 INAVO120 trial (NCT04191499) have shown that patients with HR-positive, HER2-negative, locally advanced or metastatic breast cancer harboring PIK3CA mutations who have progressed on adjuvant anti-estrogen therapy benefit from a triplet regimen of fulvestrant (Faslodex), palbociclib (Ibrance), and the novel PI3K inhibitor inavolisib (GDC-0077). The positive findings seen in this trial highlight the possibility of developing more effective treatment approaches for these endocrine-refractory patients, he continues.

Conversely, there is a subset of patients with slower-growing, indolent disease—such as those with oligometastatic or bone-only HR-positive breast cancer—for whom CDK4/6 inhibitors may not be suitable due to their associated financial burdens, toxicities, and adverse effects, Wander adds. These patients could achieve sufficient disease control with anti-estrogen therapy alone, which highlights the need for a more tailored approach to therapy for this population, he expands.

A key unmet need in this population is identifying which patients can be effectively treated with endocrine therapy alone and which require more aggressive, upfront therapy, potentially including triplet-targeted agents, Wander states. Additionally, advancing biomarker development will be critical for optimizing treatment strategies and personalizing care across this diverse patient population, Wander concludes.