Switch to a SERD Before Clinical Progression in ESR1-Mutated Advanced Breast Cancer?

In early trials, camizestrant, a next-generation selective estrogen receptor degrader (SERD) and complete ER antagonist, demonstrated activity in patients with ESR1-mutated breast cancer. A strategy to change systemic therapy based on molecular evolution of the cancer before clinical evidence of progression has been considered a means to improve survival, but not yet convincingly proven.

In the industry-funded, phase 3 SERENA-6 trial, nearly 3300 patients with ER+/ HER2− advanced breast cancer who had received at least 6 months of first-line treatment with an aromatase inhibitor (AI) plus a CDK4/6 inhibitor, and did not have evidence of disease progression, underwent testing for ESR1 mutations in circulating tumor DNA every 2 to 3 months. Ultimately, 315 patients who tested positive for ESR1 mutations were randomized either to switch to camizestrant plus a CDK4/6 inhibitor (plus a placebo AI) or to continue an AI plus a CDK4/6 inhibitor (plus placebo in place of camizestrant).

During a median follow-up of roughly 13 months, progression-free survival (PFS) — the primary end point — favored the camizestrant group (median, 16.0 months, vs. 9.2 months in the AI group). The estimated percentage of patients who were alive without progression at 24 months was 30% versus 5%, respectively.

Grade 3 or higher adverse events occurred in 60% of the camizestrant group and 46% of the AI group. Hematologic events accounted for most of this difference.