The Food and Drug Administration late Friday granted accelerated approval to camizestrant for the first-line treatment of patients with ER-positive, HER2-negative metastatic breast cancer that carries ESR1 mutations. The agency approved the drug for use in combination with a CDK4/6 inhibitor—abemaciclib, palbociclib, or ribociclib—only after detecting an ESR1 mutation in a blood test during standard therapy. The approval comes more than three months after regulators delayed a decision on the therapy, following a thumbs-down from an advisory committee.
Camizestrant, sold under the name Etcamah, is an oral, next-generation selective estrogen receptor degrader. It acts as both a degrader and a complete estrogen receptor antagonist, stopping cancer cell growth by binding to estrogen receptors and causing them to break down. In the SERENA-6 trial, patients continued on a CDK4/6 inhibitor throughout treatment but switched from an aromatase inhibitor to camizestrant as soon as an ESR1 mutation was detected in their circulating tumor DNA.
Related: Adjunct Antipsychotics Offer Hope for Depression Treatment
The trial strategy is unique. It relies on switching treatments based on signals from a blood test rather than waiting for physical disease progression on X-rays or scans. This approach aims to intervene earlier, before the cancer becomes harder to treat. Supporters of the approval noted that while the data continues to mature, the interim results showed a significant benefit for patients who switched therapies early.
For oncologists, the shift in strategy changes how they approach treatment. The SERENA-6 trial enrolled patients who had an ESR1 mutation without evidence of disease progression and a performance status score of 0 or 1. During surveillance, ESR1 testing occurred every two to three months. The study reported that patients were eligible for the randomized portion if they had at least one evaluable lesion for baseline and repeat assessments.
Related: FDA approves Rusfertide for erythrocytosis in polycythemia vera
Statistical Breakdown of the Trial
Of 3,256 patients tested for an ESR1 mutation, 315 were assigned to switch to camizestrant or stay on an aromatase inhibitor. The primary outcome was investigator-assessed progression-free survival. At the interim analysis, the median PFS was 16.0 months for camizestrant compared to 9.2 months for the aromatase-inhibitor group, resulting in a hazard ratio of 0.44 for progression or death (95% CI, 0.31 to 0.60; P < .0001).
Quality of life metrics also favored camizestrant. The median time until deterioration in patient-reported global health status was 21.0 months with camizestrant versus 6.4 months for those continuing on an aromatase inhibitor (HR, 0.54; 95% CI, 0.34 to 0.84). The frequency of discontinuation due to adverse events was 1.3% with camizestrant and 1.9% with the aromatase inhibitor.
Related: New three-stage framework targets early arthritis detection
The data, presented in June 2025 at the American Society of Clinical Oncology annual meeting, appeared in the New England Journal of Medicine. Researchers noted that ESR1 mutations cause ER-positive tumors to become resistant to standard hormonal therapies by locking the receptor in an active state. This allows cancer to multiply even when estrogen levels are reduced to zero.
