From: oncologynewscentral.com
On Sept. 4, the U.S. Food and Drug Administration (FDA) granted accelerated approval to frontline camizestrant (Etcamah) in combination with a CDK4/6 inhibitor for patients with HR-positive, HER2-negative advanced breast cancer following the emergence of an ESR1 mutation.
Regulators based their decision on results from the randomized, double-blind, placebo-controlled, multicenter, SERENA-6 clinical trial. The phase 3 study assessed switching to camizestrant plus a CDK4/6 inhibitor versus continuing an aromatase inhibitor (AI) with a CDK4/6 inhibitor in adults with ER-positive, HER2-negative locally advanced or metastatic breast cancer with detectable ESR1 mutations.
“Today’s FDA action is welcome news as many patients with ER-positive, HER2-negative advanced breast cancer are in urgent need of new treatments that delay disease progression in the first-line setting,” Erica L. Mayer, MD, MPH, director of breast cancer clinical research at Dana-Farber Cancer Institute in Boston and lead SERENA-6 investigator in the United States, told Oncology News Central. “This approval helps to address these unmet needs through prompt intervention with the camizestrant combination to treat emergence of resistance before it causes disease progression and extend the benefit of first-line treatment to optimize outcomes.”
The approval runs counter to an FDA advisory committee decision earlier this year. In a 3-6 vote, the Oncologic Drugs Advisory Committee determined that the risks of switching to camizestrant from an AI before radiographic progression outweighed its potential benefits. During the committee meeting on April 30, several members raised concerns that without a clear overall survival (OS) benefit, it was unclear if circulating tumor DNA (ctDNA)-guided early switching improved outcomes compared with standard sequencing.
In SERENA-6, investigators assessed ESR1 mutation status through ctDNA tumor deoxyribonucleic acid testing using the Guardant360 CDx assay. The FDA also approved the assay as a companion diagnostic to identify patients eligible for treatment with an ESR1 mutation.
All participants were receiving an AI plus a CDK4/6 inhibitor for at least six months and had no evidence of disease progression. Investigators randomly assigned 315 patients in a 1:1 manner to receive either camizestrant once daily plus a CDK4/6 inhibitor or an oral AI once daily plus a CDK4/6 inhibitor.
Progression-free survival (PFS) was the primary endpoint, according to RECIST v1.1 criteria. Additionally, researchers measured OS.
The median PFS was 16 months (95% confidence interval [CI], 12.7–18.2 months) in the camizestrant group versus 9.2 months (95% CI, 7.2–9.5 months) in the AI group (hazard ratio, 0.44 [95% CI, 0.31–0.60]; P<.00001). OS data were immature at the time of the PFS analysis.
“Today’s approval will enable clinicians to promptly intervene and change therapeutic strategy at an earlier opportunity ahead of disease progression, rather than waiting until the cancer becomes harder to treat, and patient outcomes and quality of life worsen,” said SERENA-6 Investigator Kevin Kalinsky, MD, MS, from Emory University in Atlanta, in a statement by AstraZeneca, the maker of camizestrant.
Regulators included a boxed warning about the risk of arrhythmia due to QTc interval prolongation when camizestrant, an oral selective estrogen receptor degrader, is used concomitantly with QTc interval-prolonging drugs. The label also includes warnings and precautions for bradycardia and embryo-fetal toxicity.
The recommended camizestrant dosage is 75 mg once daily, with or without food, until either disease progression or unacceptable toxicity occurs. Patients should take camizestrant with a CDK4/6 inhibitor—abemaciclib, palbociclib, or ribociclib—and continue the CDK4/6 inhibitor at the dose following the detection of an ESR1 mutation.
The FDA based its decision to grant accelerated approval to the SERENA-6 regimen on PFS data measured after detection of an ESR1 mutation. Confirmatory trials are required to verify and further characterize the clinical benefit to support continued approval.
Barbara Jacoby is an award winning blogger that has contributed her writings to multiple online publications that have touched readers worldwide.