Second- or Third-Line Giredestrant Among Patients With ER-Positive, HER2-Negative Advanced Breast Cancer

According to results from the phase 2 acelERA breast cancer study, giredestrant, a nonsteroidal, oral selective estrogen receptor (ER) degrader, showed a trend toward favorable benefit to investigator-assessed progression-free survival (PFS) among previously treated patients with ESR1-mutated, ER-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer. 

“Despite the effectiveness of available [endocrine therapies] ...advanced [breast cancer] remains incurable, with significant unmet needs,” wrote Miguel Martin, MD, PhD, Gregorio Marañón General University Hospital, Madrid, Spain, and coauthors. Here, researchers compare the “efficacy and safety of giredestrant with physician’s choice of endocrine monotherapy…in the second-or third-line.”  

This study enrolled 303 post-/pre-/perimenopausal patients who experienced disease progression after ≤2 lines of systemic therapy. Patients were randomized on a 1-to-1 basis to receive either 30 mg of once daily giredestrant (n = 151) or physician’s choice of endocrine therapy (n = 152) in 28-day cycles until disease progression or unacceptable toxicity. The primary end point was investigator-assessed progression-free survival (PFS). Key secondary end points included investigator-assessed PFS by baseline ERS1 status (n = 90) and safety. 

At a median follow-up of 7.9 months, median PFS was 5.6 months in the giredestrant arm and 5.4 months in the endocrine therapy arm (hazard ratio [HR], 0.81; 95% confidence interval [CI], 0.60 to 1.10; P = .1757). Six-month PFS rate was 46.8% in the giredestrant arm and 39.6% in the endocrine therapy arm. The PFS HR was 0.60 for patients with ESR1 mutations and 0.88 for patients without ERS1 mutations. The most common adverse events occurring in ≥10% of patients included AST increase, arthralgia, ALT increase, anemia, and nausea. The most common grade 3/4 adverse events occurring in ≥3 patients in either arm included anemia, hypertension, AST increase, bone pain, and blood bilirubin increase. 

“Although the acelERA BC study did not reach statistical significance for its primary [investigator-assessed] PFS end point, there was a consistent treatment effect with giredestrant across most key subgroups and a trend toward favorable benefit among patients with ESR1-mutated tumors,” concluded Dr Martin et al.

“Hopeful results continue to emerge from studies of novel ER-targeting drugs, with a number appearing to show more activity than historically available agents in the presence of a tumor ESR1 mutation,” stated Journal of Clinical Oncology associate editor, Gini Fleming, MD, University of Chicago Medicine, Chicago, Illinois. “However their significance in the treatment algorithm for women with [ER-positive], HER2-negative breast cancer remains to be determined.” 

Source: 

Martin M, Lim E, Chavez-MacGregor M, et al. Giredestrant for estrogen receptor–positive, HER2-negative, previously treated advanced breast cancer: Results from the randomized, phase II acelERA breast cancer study. J Clin Oncol. Published online: March 27, 2024. doi:10.1200/JCO.23.01500