In a phase II study (coopERA Breast Cancer) reported in The Lancet Oncology, Sara A. Hurvitz, MD, and colleagues found that 2 weeks of the addition of neoadjuvant giredestrant—a novel nonsteroidal selective estrogen receptor (ER) degrader—to palbociclib showed a stronger antiproliferative effect (greater reduction in Ki67 score) vs anastrozole plus palbociclib in postmenopausal patients with ER-positive, HER2-negative breast cancer. Objective response rates were similar with neoadjuvant palbociclib/giredestrant vs palbociclib/anastrozole. 

Sara A. Hurvitz, MD

Study Details

In the open-label trial, 221 patients from sites in 11 countries were randomly assigned between September 2020 and June 2021 to receive palbociclib with giredestrant (n = 112) or anastrozole (n = 109). Patients initially received giredestrant at 30 mg daily or anastrozole at 1 mg daily on days 1 to 14 and then entered a 16-week phase in which palbociclib at 125 mg daily was added on days 1 to 21 of 28-day cycles for four cycles. Patients had to have a baseline Ki67 score of at least 5%. The primary endpoint was geometric mean relative Ki67 score change from baseline to week 2.

Activity

The geometric mean relative reduction of Ki67 from baseline to week 2 was –75% (95% confidence interval [CI] = –80% to –70%) with giredestrant and –67% (95% CI = –73% to –59%) with anastrozole (P = .043), meeting the study’s primary endpoint.

Among 112 evaluable patients in the palbociclib/giredestrant group vs 108 in the palbociclib/anastrozole group, pathologic complete response was achieved in 4.5% (95% CI = 1.5%–10.1%) among the former vs 4.6% (95% CI = 1.5%–10.5%) among the latter. Objective response was achieved in 50.0% (95% CI = 40.4%–59.6%) vs 49.1% (95% CI = 39.3%–58.9%) of patients.

Adverse Events

Among 112 and 109 patients in the safety population, respectively, the most common adverse events of any grade in the palbociclib/giredestrant group were neutropenia (41% vs 40% in the palbociclib/anastrozole group), asthenia (22% vs 25%), decreased neutrophil count (23% vs 22%), arthralgia (11% vs 19%), and hot flush (14% vs 15%). The most common grade 3 or 4 adverse events were neutropenia (26% vs 27%) and decreased neutrophil count (15% vs 15%). Serious adverse events occurred in 4% vs 2% of patients. No treatment-related deaths were reported.

The investigators concluded: “Giredestrant offers encouraging antiproliferative and antitumor activity and was well tolerated, both as a single agent and in combination with palbociclib. Results justify further investigation in ongoing trials.”

Dr. Hurvitz, of Fred Hutchinson Cancer Center, Seattle, is the corresponding author of The Lancet Oncology article.

Disclosure: The study was funded by F. Hoffmann–La Roche. For full disclosures of the study authors, visit thelancet.com.