Camizestrant Combo Shows Antitumor Activity in ER+, HER2– Advanced Breast Cancer

Results from the phase 1 SERENA-1 trial (NCT03616587) revealed that camizestrant is well tolerated and showed antitumor activity in combination with CDK4/6 inhibitors (CDK4/6i) in patients with estrogen receptor–positive (ER+), HER2-negative (HER2–) advanced breast cancer.¹

As of the cutoff date of September 16, 2024, 53 patients had been treated with camizestrant plus abemaciclib (Verzenio), 78 patients treated with camizestrant plus palbociclib (Ibrance), and 60 patients treated with camizestrant plus ribociclib (Kisqali). Patients had a median of 2 prior lines of therapy for advanced disease. Of the total patients, 83% had received a prior CDK4/6i, and 59% had received prior fulvestrant.

Across all combinations, the clinical benefit rate (CBR) at 24 weeks was 49.5%, and the median progression-free survival (PFS) was 7.4 months (95% CI, 5.3-9.3). Antitumor activity was also observed across all combinations.

For patients who received camizestrant with abemaciclib, palbociclib, and ribociclib, the confirmed objective response rates with measurable disease at baseline were 34.1% (n = 14/41), 9.7% (n = 6/62), and 14.3% (n = 6/42), respectively. The CBRs were 54.9% (n = 28/51), 43.6% (n = 34/78), and 52.5% (n = 31/59), respectively. The median PFS for each was 10.8 months (95% CI, 4.6-24.8), 4.6 months (95% CI, 3.7-8.2), and 8.1 months (95% CI, 5.4-not calculated), respectively.

Safety Results of the SERENA-1 Trial

The most common treatment-emergent adverse events (AEs) for camizestrant at 75 mg plus each CDK4/6i were diarrhea (with abemaciclib, 87.5%) and neutropenia (with palbociclib, 80%; with ribociclib, 32.1% for 400 mg and 53.1% for 600 mg).¹

“Overall, the safety profile for each CDK4/6i administered in combination with camizestrant was consistent with their known profiles as monotherapy and in combination with other ETs,” the study authors wrote. “The safety profile of camizestrant when dosed in combination with each of the CDK4/6i was also consistent with its monotherapy profile. These observations, in addition to there being few instances of AEs leading to dose reduction or discontinuation of camizestrant, demonstrate that camizestrant is well tolerated, with no additive toxicity when combined with any of these [3] CDK4/6i.”

For camizestrant (75, 150, and 300 mg) plus palbociclib, neutropenia was both the most common treatment-emergent AE of any grade (80.0%, 83.3%, and 75.9%, respectively) and the most common grade 3 or higher treatment-emergent AE (56.0%, 66.7%, and 62.1%). For camizestrant (75 mg) plus ribociclib (400 and 600 mg), the most common treatment-emergent AEs of any grade were neutropenia (32.1% and 53.1%, respectively) and nausea (35.7% and 43.8%), and the most common grade 3 or higher treatment-emergent AE was neutropenia (10.7% and 43.8%). There were no reports of AEs leading to discontinuation of camizestrant only.

Grade 1 photopsia and sinus bradycardia were observed across all arms. In the camizestrant 75-mg combinations with CDK4/6i arm, photopsia was reported in 27.5% (n = 30/109) of patients. A total of 51.4% (n = 56/109) of patients reported a vision-related AE, with a median onset of 7 days. Of the patients reporting AEs, 64.3% (n = 36/56) reported resolution either during or following cessation of camizestrant. However, 19.6% (n = 11/56) of patients were still receiving camizestrant at the data cutoff and had ongoing visual effects.

Electrocardiograms were performed throughout the study, showing that camizestrant treatment was associated with dose- and time-dependent reversible reductions in resting heart rate, with a gradual decrease to a stable nadir over approximately 14 days.

Additional Studies of Camizestrant

The safety and efficacy of camizestrant monotherapy have also been evaluated in the phase 2 SERENA-2 study (NCT04214288),² where camizestrant demonstrated superior PFS over fulvestrant in patients with pretreated ER+, HER2– advanced breast cancer. The phase 3 SERENA-6 trial (NCT04964934) yielded statistically significant and clinically meaningful improvement in PFS vs continuing aromatase inhibitor plus CDK4/6i in patients with hormone receptor–positive, HER2– advanced breast cancer.¹

REFERENCES:

1. Baird R, de las Heras B, Ruiz-Borrego M, et al. Camizestrant in combination with three globally approved CDK4/6 Inhibitors in women with ER+, HER2- advanced breast cancer: results from SERENA-1. Clin Cancer Res (2025) 31 (20): 4244–4254. doi:10.1158/1078-0432.CCR-25-1198

2. A study to investigate efficacy and safety with oral AZD9833 compared with intramuscular fulvestrant in post-menopausal women at least 18 years of age with advanced ER-positive HER2 negative breast cancer (SERENA-2). ClinicalTrials.gov. Updated August 7, 2025. Accessed November 3, 2025. https://clinicaltrials.gov/study/NCT04214288