SERENA-2: Camizestrant vs Fulvestrant in Advanced ER+/HER2- Breast Cancer

This is a synopsis of an Insights series featuring Kevin Kalinsky, MD, MS, of Winship Cancer Institute of Emory University, and Erica L. Mayer, MD, MPH, of Dana-Farber Cancer Institute.

Dr Erica Mayer discussed recent phase II data on the investigational oral selective estrogen receptor degrader [SERD] camizestrant from the SERENA-2 trial. Camizestrant was compared to the injectable fulvestrant in patients previously treated with endocrine therapy, about half having prior CDK4/6 inhibitors. Crossover was allowed on progression.

The primary endpoint of progression-free survival significantly improved with camizestrant over fulvestrant in the intention-to-treat population. A preplanned analysis of the 40% of patients with baseline ESR1 mutations showed an even greater progression-free survival difference favoring camizestrant arms over fulvestrant. No meaningful efficacy differences were evident in ESR1 wild-type disease. These results aligned with prior studies suggesting SERDs may provide preferential benefit in ESR1-mutated states.

Camizestrant was reasonably well tolerated. Like other oral SERDs, low grade nausea and vomiting occurred. Unique but rare adverse effects included visual changes called phosphenes and asymptomatic bradycardia, both dose-dependent. Encouragingly, the 75-mg selected phase III dose showed lowest rates of these unusual toxicities vs higher camizestrant doses.

Dr Kevin Kalinsky concurred the SERENA-2 efficacy and safety data support further camizestrant development, noting several ongoing trials in both metastatic and adjuvant settings. He raised the future challenge of selecting among multiple approved oral SERDs. Beyond ESR1 mutation status predicting enhanced SERD activity, factors like tolerability differences and specificity for certain ESR1 mutations may ultimately guide choice. Early camizestrant analyses did not suggest efficacy variations by exact mutation type, but this warrants further study as precision targeting continues progressing.

Overall, Drs Mayer and Kalinsky are optimistic about the expanding oral SERD class. Multiple agents with distinct toxicity profiles are progressing through pivotal evaluation as monotherapy or combinations for HR+ breast cancer. Defining optimal treatment sequencing and patient selection biomarkers, potentially including specific ESR1 mutation variants, will be key to maximizing these next-generation endocrine agents’ impact across disease settings.

*Video synopsis is AI-generated and reviewed by OncLive editorial staff.