The FDA has approved two new treatment options for patients with ESR1-mutated, hormone receptor-positive (HR+), HER2-negative advanced or metastatic breast cancer — and they represent two different philosophies on when to switch therapy.

First up: imlunestrant (Inluriyo, Eli Lilly) combined with abemaciclib (Verzenio), approved September 21, 2026, for patients whose disease has progressed after at least one line of endocrine therapy. Just two weeks earlier, the FDA granted accelerated approval to camizestrant (Etcamah, AstraZeneca) plus a CDK4/6 inhibitor — but with a key distinction: the switch happens before progression, as soon as an ESR1 mutation is detected via ctDNA testing. That makes it the first-ever FDA approval of a cancer treatment change based on ctDNA rather than imaging-confirmed progression.

Both approvals come with companion diagnostics to detect ESR1 mutations. About 30–50% of patients develop ESR1 mutations during aromatase inhibitor therapy, driving resistance — making these approvals clinically significant.

By the Numbers:

• Imlunestrant + abemaciclib (EMBER-3 subgroup): median PFS 11.1 months vs. 5.5 months with imlunestrant alone
• Camizestrant + CDK4/6 inhibitor (SERENA-6): median PFS 16 months vs. 9.2 months with continued AI
• Camizestrant reduced risk of progression or death by 56% (HR = 0.44)
• Grade 3/4 neutropenia with imlunestrant combo: 21%; ILD: 3%

Why it matters: These back-to-back approvals give oncologists two distinct strategies for tackling ESR1-driven resistance — one reactive, one proactive. The debate over when to switch (at mutation detection vs. at progression) remains active, and confirmatory trials are ongoing. But the era of ctDNA-guided treatment decisions in breast cancer has officially arrived.