A recent study presented at the 2024 San Antonio Breast Cancer Symposium demonstrated exciting data from the SERENA-1 clinical trial, exploring the safety and efficacy of camizestrant, an investigational oral selective estrogen receptor degrader, in combination with ribociclib, a CDK4/6 inhibitor, for women with estrogen receptor (ER)-positive/HER2-negative advanced breast cancer. The results suggest that this combination therapy may be a safe and effective option for this patient population, particularly patients with detectable ESR1 mutations.
SERENA-1 is a phase 1, multipart, open-label study of camizestrant plus ribociclib in patients with advanced breast cancer who had received prior treatment, including chemotherapy, CDK4/6 inhibitors, and fulvestrant. Researchers investigated the combination of camizestrant 75 mg once daily with either 400 mg or 600 mg of ribociclib, administered intermittently (21 days on, 7 days off). Objectives included assessment of antitumor response and pharmacokinetics.
As of September 26, 2024, 60 patients were enrolled in the study; 28 received camizestrant plus ribociclib 400 mg, and 32 patients received camizestrant plus ribociclib 600 mg. Steady-state ribociclib exposure, when combined with camizestrant 75 mg, was similar to the simulations derived from a published population pharmacokinetic (popPK) model for ribociclib monotherapy. The exposure to camizestrant 75 mg in combination with either ribociclib 400 mg or ribociclib 600 mg was comparable with the exposure predicted from a popPK simulation of camizestrant monotherapy at 150 mg.
One of the key findings was the favorable safety profile of the combination therapy. Adverse events (AEs) were generally consistent with those observed for each drug individually. The most common AEs related to camizestrant were visual effects and bradycardia, both occurring at a mild grade 1 severity. Neutropenia, nausea, and fatigue were the most frequent AEs attributed to ribociclib. While some patients experienced AEs requiring treatment interruptions, these were manageable.
The study also demonstrated the potential of the combination therapy to suppress ESR1 mutations, which are often associated with resistance to endocrine therapy. In patients with detectable ESR1 mutations at baseline (43%), 86.8% experienced a reduction >50% in these mutations after treatment, with half of those patients achieving complete clearance. This finding suggests that the combination therapy may effectively target and overcome resistance mechanisms, potentially leading to better treatment outcomes.
While the study is still ongoing, the preliminary results are encouraging. This combination therapy is also being further evaluated in the phase 3 SERENA-6 trial, which will compare camizestrant plus a CDK4/6 inhibitor with an aromatase inhibitor plus a CDK4/6 inhibitor in patients with detectable ESR1 mutations during first-line therapy. The results of SERENA-6 will provide further insights into the role of camizestrant in the treatment of ER-positive/HER2-negative advanced breast cancer, potentially shaping future treatment strategies for this patient population.
Baird R, et al. Results from SERENA-1 parts K/L: a phase 1 study of the next-generation oral selective estrogen receptor degrader (SERD) camizestrant (AZD9833) in combination with ribociclib in women with ER-positive, HER2-negative advanced breast cancer. Presented at: San Antonio Breast Cancer Symposium. December 10, 2024; San Antonio, TX. Abstract SESS-1686.