In a phase II trial (SERENA-2) reported in The Lancet Oncology, Oliveira et al found that the next-generation oral selective estrogen receptor degrader (SERD) camizestrant improved progression-free survival vs fulvestrant in postmenopausal women with estrogen receptor (ER)-positive, HER2-negative advanced breast cancer.

Study Details

In the open-label trial, 240 patients from sites in Asia, Europe, Middle East, and North America were randomly assigned 1:1:1:1 between May 2020 and August 2021 to receive camizestrant once daily at 75 mg (n = 74), 150 mg (n = 73), or 300 mg (n = 20) or intramuscular fulvestrant 500 mg on days 1, 15, and 29 and once every 4 weeks thereafter. All patients had experienced cancer recurrence or progression on at least one line of endocrine therapy and had no more than one previous endocrine therapy in the advanced setting.

Treatment continued until disease progression or unacceptable toxicity. Enrollment into the group receiving camizestrant at 300 mg was stopped early, after evidence from a phase I trial indicated no additional activity at this dose vs 150 mg. 

The primary endpoint was investigator-assessed progression-free survival. No formal statistical comparison for the efficacy analysis of camizestrant at 300 mg vs fulvestrant was performed.

Progression-Free Survival

Median follow-up ranged from 14.7 to 16.6 months across the 3 groups included in the analysis. Compared with median progression-free survival of 3.7 months (90% confidence interval [CI] = 2.0–6.0 months) in the fulvestrant group, median progression-free survival was 7.2 months (90% CI = 3.7–10.9 months) among those receiving camizestrant at 75 mg (hazard ratio [HR] = 0.59, 90% CI = 0.42–0.82, P = .017) and 7.7 months (90% CI = 5.5–12.9) in those receiving camizestrant at 150 mg (HR = 0.64, 90% CI = 0.46–0.89, P = .0090).

Adverse Events  

Treatment-related adverse events of any grade occurred in 39 (53%) of 74 patients receiving camizestrant at 75 mg, 49 (67%) of 73 patients receiving camizestrant at 150 mg, 14 (70%) of 20 patients receiving camizestrant at 300 mg, and 13 (18%) of 73 patients in the fulvestrant group. No individual grade ≥ 3 adverse event occurred in more than two patients in any group.

Serious adverse events occurred in 8%, 10%, and 10% of the three camizestrant groups and in 5% of patients in the fulvestrant group. Any-grade photopsia occurred in 12%, 25%, and 35% of the three camizestrant groups and in 0% of the fulvestrant group. Any-grade bradycardia occurred in 0%, 16%, and 30% of the three camizestrant groups and in 0% of the fulvestrant group. No treatment-related deaths were reported.  

The investigators concluded: “Camizestrant at 75 and 150 mg showed a significant benefit in progression-free survival vs fulvestrant. These results support further development of camizestrant for the treatment of estrogen receptor–positive, HER2-negative breast cancer.”

Mafalda Oliveira, MD, of Vall d’Hebron University Hospital and Breast Cancer Group, Vall d’Hebron Institute of Oncology, Barcelona, is the corresponding author for The Lancet Oncology article.

Disclosure: The study was funded by AstraZeneca. For full disclosure information of all study authors, visit The Lancet Oncology.