Editor's Note: The SERENA-2 study evaluated the efficacy and safety of different doses of Camizestrant (75 mg, 150 mg) compared to fulvestrant in patients with advanced ER+/HER2- breast cancer. The results showed that the median PFS in the Camizestrant groups was similar regardless of ESR1m status or dosage. Researchers further conducted an exploratory analysis of the SERENA-2 study to examine the suppression of ESR1m ctDNA in patients treated with Camizestrant compared to fulvestrant and its correlation with PFS. The findings of this exploratory analysis were presented at the 2024 ESMO BC conference, and this article provides a summary of the results.In the phase II SERENA-2 clinical trial, Camizestrant, a next-generation selective estrogen receptor degrader, demonstrated a significant improvement in progression-free survival (PFS) in patients with ER+/HER2- metastatic breast cancer (mBC) compared to fulvestrant. This study further investigated the inhibitory effect of Camizestrant on ESR1-mutant circulating tumor DNA (ctDNA) and its correlation with PFS.
The study combined data from patients in both Camizestrant dose groups (75 mg and 150 mg, totaling 147 patients) and compared them to patients in the fulvestrant 500 mg group (73 patients). ctDNA from plasma samples collected at baseline, on day 1 of cycle 2 (C2D1), and at disease progression was analyzed using next-generation sequencing.
Camizestrant treatment resulted in a more than 50% reduction in ESR1m variant allele frequency (VAF) by C2D1 in 84% of patients. Compared to fulvestrant, Camizestrant was more effective in reducing ESR1m levels both during treatment and at disease progression. Additionally, in 56% of patients treated with Camizestrant, ESR1m remained suppressed even at the time of disease progression. The reduction in ESR1m ctDNA induced by Camizestrant was associated with a prolonged PFS, a correlation not observed in patients treated with fulvestrant.
Camizestrant was more effective than fulvestrant in inhibiting ESR1m ctDNA, and the level of inhibition at C2D1 was associated with longer PFS, suggesting that early changes in ctDNA may predict a better response to Camizestrant treatment. The ongoing SERENA-6 trial will prospectively test the efficacy of Camizestrant in patients with detectable ESR1m.
