Camizestrant, an investigational oral selective estrogen receptor degrader (SERD), has demonstrated superior progression-free survival (PFS) compared to fulvestrant in patients with estrogen receptor (ER)-positive, HER2-negative advanced breast cancer. The findings, from the phase 2 SERENA-2 trial, were published in The Lancet Oncology, potentially marking a significant advancement in endocrine therapy for this patient population.
The SERENA-2 trial (NCT04214288) enrolled 240 patients with advanced ER-positive, HER2-negative breast cancer who had experienced disease progression on at least one prior line of endocrine therapy but no more than one in the advanced setting. Patients were randomized to receive fulvestrant 500 mg (n=73) or camizestrant at 75 mg (n=74), 150 mg (n=73), or 300 mg (n=20). Enrollment in the 300 mg arm was halted early, and efficacy analysis was not performed for this group.
Progression-Free Survival Benefit
After a median follow-up of 16.6 months for the camizestrant 75 mg arm, 16.3 months for the camizestrant 150 mg arm, and 14.7 months for the fulvestrant arm, camizestrant demonstrated a statistically significant improvement in PFS. Median PFS by investigator assessment was 7.2 months with camizestrant 75 mg (HR, 0.59; 90% CI, 0.42-0.82; P = .017) and 7.7 months with camizestrant 150 mg (HR, 0.64; 90% CI, 0.46-0.89; P = .0090), compared to 3.7 months with fulvestrant. Blinded independent review yielded similar PFS results.
Objective Response Rate and Overall Survival
The objective response rate (ORR) was 12% in the fulvestrant arm, 16% in the camizestrant 75 mg arm (odds ratio [OR], 1.42; 90% CI, 0.63-3.31), and 17% in the camizestrant 150 mg arm (OR, 1.57; 90% CI, 0.69-3.67). Overall survival (OS) data were not mature at the data cutoff. The median OS was 20.5 months in the fulvestrant arm and not reached in either of the camizestrant arms.
Safety Profile
Treatment-related adverse events (TRAEs) were more frequent with camizestrant. TRAEs occurred in 18% of patients receiving fulvestrant, 53% of those receiving camizestrant 75 mg, and 67% of those receiving camizestrant 150 mg. No treatment-related deaths were reported. Grade 3-4 TRAEs were observed in 1% of patients receiving camizestrant 75 mg and 3% of those receiving camizestrant 150 mg, with no grade 3-4 TRAEs in the fulvestrant arm.
Clinical Implications
"Camizestrant at 75 and 150 mg showed a significant benefit in progression-free survival versus fulvestrant," the researchers concluded. "These results support further development of camizestrant for the treatment of estrogen receptor-positive, HER2-negative breast cancer."
The study suggests that camizestrant could provide a valuable alternative for patients with ER-positive, HER2-negative breast cancer who have progressed on prior endocrine therapy. Further research is warranted to evaluate the long-term efficacy and safety of camizestrant in larger patient populations.
