Dr McCann on the Standard of Care for Managing ER+/HER2– Advanced Breast Cancer

“The standard of care is still an aromatase inhibitor [AI] plus a CDK4/6 inhibitor in patients [with ER-positive, HER2-negative advanced breast cancer] who haven’t developed resistance to the AI.”

Kelly E. McCann, MD, PhD, an assistant professor of Medicine and a breast medical oncologist at UCLA Health, detailed the standard of care and novel approaches for the treatment of patients with estrogen receptor (ER)–positive, HER2-negative advanced or metastatic breast cancer, along with remaining unmet needs.

Updated data from the phase 3 VERITAC-2 trial (NCT05654623), presented at the 2025 ASCO Annual Meeting, revealed that the oral proteolysis-targeting chimera (PROTAC) vepdegestrant demonstrated statistically significant and clinically meaningful improvement in progression-free survival (PFS) per blinded independent central review (BICR) compared with fulvestrant (Faslodex) for the treatment of patients with ESR1-mutated ER-positive, HER2-negative advanced breast cancer. Of note, in patients with ESR1-mutated disease, the median PFS by BICR was 5.0 months (95% CI, 3.7-7.4) vs 2.1 months (95% CI, 1.9-3.5) in the vepdegestrant (n = 136) and fulvestrant (n = 134) arms, respectively (HR, 0.57; 95% CI, 0.42-0.77; 2-sided P < .001). Furthermore, patients with ESR1-mutated disease had an overall response rate (ORR) of 18.6% and 4.0% in the respective arms (odds ratio, 5.45; 95% CI, 1.69-22.73; P = .001).

However, although the novel PROTAC showed promise, an aromatase inhibitor (AI) plus a CDK4/6 inhibitor remains the standard of care for this patient population, particularly in those who have not developed resistance to the AI, McCann began. In her own practice, she uses fulvestrant plus a PI3K inhibitor, which opens the door to many drugs, including alpelisib (Piqray), capivasertib (Truqap), and everolimus (Avastin), she noted.

Beyond the standard of care, other questions remain, such as how the oral selective ER degrader (SERD) elacestrant (Orserdu) or vepegestrant—if FDA-approved—will be used for the treatment of patients with ESR1-mutated disease, McCann continued. In her practice, she currently uses doublet strategies in the beginning, although endocrine resistance develops, which leads patients to require chemotherapy, she said. Therefore, identifying proper sequencing strategies is also key, McCann concluded.