What You Should Know

  • The phase III SERENA-6 study found that proactively monitoring for ESR1 mutations with routine ctDNA testing — and switching to camizestrant before radiographic progression — reduced the risk of disease progression or death by 56% in patients with metastatic HR+/HER2- breast cancer on first-line AI plus CDK4/6 therapy.
  • A co-author of the study, Dr. Erica Mayer of Dana-Farber Cancer Institute believes this “SERENA-6 approach” could modestly expand ctDNA testing in the metastatic setting while likely keeping mutation testing unchanged in early-stage disease.

In conversation with SurvivorNet, leading breast oncologist and clinical researcher Dr. Erica Mayer expressed her views on how ESR-1 testing–amongst metastatic HR+/HER2- breast cancer patients–could shift as a result of what she calls “the SERENA-6 approach.”

What makes the phase III SERENA-6 trial unique is its proactive ctDNA monitoring strategy. For the first time, patients undergo blood testing every two to three months—approximately four times per year, according to Dr. Mayer—to detect emerging ESR1 mutations before radiographic progression. If an ESR1 mutation is identified, treatment can be switched preemptively in an effort to delay or prevent clinical progression.

SERENA-6 Study Design and Results

The SERENA-6 trial was designed to intervene earlier in this resistance process. The global study evaluates the oral selective estrogen receptor degrader (SERD) camizestrant in patients receiving first-line therapy with an aromatase inhibitor plus a CDK4/6 inhibitor. Eligible patients must have had at least six months of stable disease before entering the screening phase.

  • Population: Advanced (locally advanced or metastatic) HR+ / HER2- breast cancer not amenable to curative therapy; currently on first-line endocrine therapy with an AI plus a CDK4/6 inhibitor for at least 6 months.
  • Trial Mechanism: The trial involved monitoring patients on 1L AI + CDK4/6 inhibitor therapy for ESR1 mutations via liquid biopsy. Upon detection of an ESR1 mutation (but without radiographic progression), patients were randomized to switch to camizestrant or continue the AI.
  • Significantly Improved PFS: Switching to camizestrant upon detection of ESR1 mutations resulted in a 56% reduction in the risk of disease progression or death compared to continuing aromatase inhibitor (AI) treatment.

A Co-Author’s Takeaways

“The current ASCO guidance for ESR-1 testing would be to obtain testing at time of diagnosis of metastatic disease, which I typically do both by ctDNA as well as tissue if I have metastic biopsy for confirmation. And, then, to test again at time of disease progression,” Dr. Mayer says. “It is possible that the SERENA-6 approach will change this, and we may begin sending ctDNA in patients who have at least six months of stability on first line therapy.”

Dr. Mayer notes that if this approach becomes standard, it could modestly expand the use of ctDNA in metastatic care. “The SERENA-6 approach is essentially sending ctDNA four times a year. It’s not a dramatic change, but it would be at times of restaging,” Dr. Mayer says. “We currently do not look for actual mutations in the early stage setting as that’s not part of our treatment paradigm. So, I don’t see us doing more testing or testing in a different way in our early stage patients, but there could be more expansive use of ctDNA in the metastatic setting pending what happens with the SERENA-6 approach.”