Dr Cobain on Second- and Later-Line Treatment Options in HR+/HER2– Breast Cancer

Erin Frances Cobain, MD, medical oncologist, co-director, Breast Cancer Clinical Research Team, Rogel Cancer Center, University of Michigan, details the expanding landscape of treatment options in the second line and beyond for patients with hormone receptor (HR)–positive, HER2-negative metastatic breast cancer.

Changes in the later-line treatment of this patient population stem from the FDA's approvals of targeted inhibitors. In May 2019, the regulatory agency approved the PI3K inhibitor alpelisib (Piqray) for use in combination with fulvestrant (Faslodex) as a treatment for postmenopausal women, and men, with HR-positive, HER2-negative, PIK3CA-mutated, advanced or metastatic breast cancer following progression on or after an endocrine-based regimen. Furthermore, in November 2023, the FDA approved capivasertib (Truqap) in combination with fulvestrant for the treatment of adult patients with HR–positive, HER2-negative, locally advanced or metastatic breast cancer harboring 1 or more PIK3CA, AKT1, or PTEN alterations, as detected by an FDA-approved test, following progression on at least 1 endocrine-based regimen in the metastatic setting or recurrence on or within 12 months of completing adjuvant therapy.

Additionally, in January 2023, the FDA approved elacestrant (Orserdu) for the treatment of postmenopausal women or adult men with estrogen receptor–positive, HER2-negative, ESR1-mutated advanced or metastatic breast cancer with disease progression following at least 1 line of endocrine therapy.

Cobain explains that the use of any of these agents in the second-line setting or beyond is contingent upon the presence of specific somatic molecular alterations in the patient's tumor, as indicated with each agent. These alteration-specific approvals highlight the necessity of molecular testing strategies employed in clinical practice, Cobain continues, noting that by elucidating the nuanced interplay between molecular profiles and treatment selection, clinicians can optimize therapeutic decisions for patients with HR-positive metastatic breast cancer.

By integrating molecular profiling into routine clinical practice, oncologists can tailor treatment regimens to individual patient profiles, thereby optimizing therapeutic efficacy and minimizing adverse events, she says.

The growing armamentarium of targeted inhibitors highlights a paradigm shift in the treatment of patients with HR-positive, HER2-negative metastatic breast cancer, Cobain explains. Through a nuanced understanding of molecular profiles and judicious utilization of molecular testing, clinicians can navigate this complex landscape with precision, ultimately improving patient outcomes and quality of life, she concludes.