In a phase II trial (SERENA-2) published in The Lancet Oncology, researchers found that the next-generation oral selective estrogen receptor degrader (SERD) camizestrant improved progression-free survival compared to fulvestrant in postmenopausal women with estrogen receptor (ER)-positive, HER2-negative advanced breast cancer. The study suggests a potential new treatment option for this patient population, addressing the need for more effective endocrine therapies.
The open-label trial involved 240 patients across sites in Asia, Europe, the Middle East, and North America. Participants were randomly assigned (1:1:1:1) 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 then once every 4 weeks. All patients had experienced cancer recurrence or progression on at least one line of endocrine therapy and had no more than one prior endocrine therapy in the advanced setting. The 300mg camizestrant arm was stopped early due to phase 1 data showing no additional benefit over the 150mg dose.
Treatment continued until disease progression or unacceptable toxicity. The primary endpoint was investigator-assessed progression-free survival. No formal statistical comparison was performed for the efficacy analysis of camizestrant at 300 mg vs fulvestrant.
Progression-Free Survival
Median follow-up ranged from 14.7 to 16.6 months across the groups included in the analysis. The 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). In comparison, the fulvestrant group had a median progression-free survival of 3.7 months (90% confidence interval [CI] = 2.0–6.0 months).
Safety Profile
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.
According to the investigators, "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."
