Camizestrant versus fulvestrant in postmenopausal advanced breast cancer

The next-generation oral selective estrogen receptor degrader (SERD) and complete estrogen receptor antagonist camizestrant might be a valuable treatment option for patients with estrogen receptor positive/HER2 negative advanced breast cancer, as shown by results of the SERENA-2 trial recently published on The Lancet Oncology.

SERENA-2 is an open-label, randomized, phase 2 multicenter trial involving post-menopausal patients with estrogen receptor-positive, HER2-negative advanced breast cancer; 240 patients were randomized to receive oral camizestrant once daily at 75 mg, 150 mg, or 300 mg (until the 300 mg group was closed), or the first SERD approved fulvestrant (intramuscularly at 500 mg). At a median follow up of more than 16 months for camizestrant and 14,7 months for fulvestrant, median progression-free survival was 7,2 months with camizestrant 75 mg, 7,7 months with camizestrant 150 mg, and 3,7 months with fulvestrant; serious treatment-emergent adverse events occurred in 8% of patients in the camizestrant 75 mg group, 10% of patients in the camizestrant 150 mg group, 10% of patients in the camizestrant 300 mg group, and 5% of patients in the fulvestrant group. There were few dose adjustments and no new safety concerns were identified. Both 75 mg and 150 mg daily oral doses of camizestrant monotherapy improved progression-free survival versus fulvestrant; the progression-free survival benefit was noted across clinically relevant subgroups of patients, such as patients with previous CDK4/6 inhibitor use, those with liver and/or lung metastases, and those with detectable ESR1 mutations in circulating tumour DNA at baseline, whereas the previous generation SERD fulvestrant is clinically effective against only wild-type ESR1 disease biology. As authors conclude, «The results of SERENA-2 complement other data in the camizestrant programme to support the selection of 75 mg as the optimal dose for further development, balancing maximal efficacy with lower frequency of reported adverse events. These data support the next- generation SERD camizestrant as a potentially valuable treatment option to patients with early and advanced breast cancer».