Giredestrant shows promise in early breast cancer
Women with early breast cancer who were treated with the novel anti-hormonal therapy giredestrant saw reductions in tumor activity before surgery, according to interim data presented at the European Society for Medical Oncology Congress.
“Giredestrant has shown early evidence of safety and efficacy in the phase I, non-comparative study setting but had not yet been compared to the standard-of-care aromatase inhibitor,” author Sara A. Hurvitz, MD, director of the Breast Cancer Clinical Research Program at the UCLA Jonsson Comprehensive Cancer Center, told Healio.
The study was designed to compare the Ki67 change in patients who received giredestrant, which is manufactured by Roche, compared with those who received anastrozole. Ki67 is a protein that is expressed when the cancer cell is dividing. Researchers said that a reduction in Ki67 is associated with better outcomes.
“Data from this study would be used as proof of concept to support larger phase III trials including lidERA and persevERA, which are comparing giredestrant to standard-of-care aromatase inhibitors in the curative and metastatic settings, respectively,” Hurvitz said.
The study enrolled 202 postmenopausal women diagnosed with untreated estrogen receptor (ER)-positive and human epidermal growth factor receptor-2 (HER2)-negative early breast cancers, including 108 safety-evaluable patients and 83 efficacy-evaluable patients.
Half of the patients were randomly assigned to receive 2 weeks of the oral selective estrogen receptor degrader (SERD) giredestrant, and half received the standard-of-care aromatase inhibitor (AI) anastrozole.
After 2 weeks, palbociclib was given with giredestrant or anastrozole for the 14-week neoadjuvant phase before surgery. Biopsies were performed before the therapy began and at the 2-week mark to evaluate the percentage of cells expressing Ki67.
Patients who were treated with giredestrant for 2 weeks experienced more than an 80% drop (95% CI, 72%-85%; P = .0222) from baseline in their tumor Ki67. Patients who were treated with anastrozole saw a 67% reduction (95% CI, 56%-75%; P = .0222).
Also, among patients with baseline Ki67 of 20% or greater, a greater proportion of those who were treated with giredestrant saw consistent Ki67 suppression compared with those who were treated with anastrozole — 83% vs. 71%. Of those patients with baseline Ki67 of less than 20%, 65% who were treated with giredestrant saw consistent Ki67 suppression, compared with 24% of patients who were treated with anastrozole.
At week 2, 25% of the tumors treated with giredestrant exhibited complete cell cycle arrest, compared with 5% of those treated with anastrozole (delta change, 20%; 95% CI, –37% to –3%).
Finally, the percentage of patients with adverse events (AEs) related to giredestrant (28%) was smaller than that of patients with AEs related to anastrozole (38%), and there were no serious AEs or AEs of grade 3 or higher related to giredestrant.
“The relative change in Ki67 appears to be better with giredestrant than with anastrozole after just 2 weeks of therapy,” Hurvitz said.
“Though the difference did not meet our prespecified P value for statistical significance at the interim analysis, the trend is in the right direction,” she continued. “We will be presenting the primary analysis, including data from the rest of the patients enrolled, at an upcoming meeting.”
According to the researchers, more than 180,000 women are diagnosed with ER-positive breast cancer each year in the United States, comprising more than two-thirds of all diagnosed breast cancers. Up to half of women with ER-positive disease will develop treatment resistance to current therapies.
Oral SERDs are ER downregulators taken as pills instead of as injections, and they are becoming a more widely studied alternative to AIs, the researchers said.
Though AIs are now the standard of care for women with ER-positive early breast cancer, they do not always work in the long term, the researchers continued. New generations of oral SERDs are being developed to better overcome drug resistance.
The researchers concluded that giredestrant may be another option for women with ER-positive breast cancer.
“These data, while promising, are not yet practice changing, but do lend support to the ongoing accrual to the larger phase III trials,” Hurvitz said.