AstraZeneca has produced some fresh data to back up its blockbuster ambitions for camizestrant, tying the oral SERD to a 56% improvement in progression-free survival (PFS) in a phase 3 breast cancer study.
The Serena-6 study had a novel design that reflected an unmet need in individuals with HR-positive, HER2-negative advanced breast cancer. All 315 patients received an aromatase inhibitor and a CDK4/6 inhibitor—either Eli Lilly’s Verzenio, Novartis’ Kisqali or Pfizer’s Ibrance—as their first-line treatment.
Physicians then monitored circulating tumor DNA to spot ESR1 mutations. If a mutation was found before disease progression, patients switched to camizestrant and stayed on the CDK4/6 drug.
AstraZeneca revealed back in February that, based on an interim readout, the trial had hit its primary endpoint of PFS but saved the detailed data for the American Society of Clinical Oncology (ASCO) meeting in Chicago on Sunday. Specifically, patients who were moved up to camizestrant and a CDK4/6 inhibitor had a median PFS of 16 months, compared to 9.2 months for those who only received the first-line treatment of an aromatase inhibitor and a CDK4/6 inhibitor.
As with the previous announcement in February, AstraZeneca reaffirmed that data on the key secondary endpoints of overall survival or time to second disease progression (PFS2) had been immature at the time of the interim analysis. All the drugmaker had to add yesterday was that “a trend toward extended treatment benefit” has so far been observed when it came to PFS2.
The company instead wanted to focus on an exploratory endpoint of “time to deterioration in quality of life.” Here, AstraZeneca could point to a 47% reduction in deterioration of global health status and quality of life among the camizestrant cohort—with a median time of 23 months before these patients saw their health status deteriorate compared to 6.4 months for other patients.
“As the first pivotal trial to demonstrate the clinical value of monitoring circulating tumour DNA to detect emerging resistance and change therapy at the earliest opportunity; SERENA-6 is redefining the clinical paradigm in breast cancer,” Susan Galbraith, Ph.D., executive vice president of oncology R&D at AstraZeneca, said in a June 1 release.
“Camizestrant is the first and only next-generation oral SERD and complete estrogen receptor antagonist to demonstrate benefit in combination with widely approved CDK4/6 inhibitors in this first-line setting, and these results support its potential as a new standard-of-care endocrine therapy backbone in the treatment of HR-positive breast cancer,” Galbraith added.
When it came to safety, 60% of patients receiving camizestrant experienced adverse events of grade 3 or higher, compared to 40% of the comparator cohort. But AstraZeneca argued this was “consistent with the longer duration of exposure to the combination of camizestrant and CDK4/6 inhibitors in the trial.”
The majority of these side effects were hematological events typically associated with CDK4/6 inhibitor treatment and included neutropenia and leukopenia—abnormally low concentration of a type of white blood cell—and anemia.
The PFS endpoint is the first of a series of milestones for the program. AstraZeneca is running another trial in a broader first-line population and two adjuvant studies. Through the program, the company is aiming to establish camizestrant as a new backbone therapy and hit a peak sales target that AstraZeneca CEO Pascal Soriot has set at more than $5 billion.
But AstraZeneca could face competition. Lilly reported phase 3 data on its oral SERD imlunestrant in patients who progressed on an aromatase inhibitor late last year. Roche is aiming to have data on giredestrant, its challenger for the market, sometime from mid-2025 onward. AstraZeneca sees the safety profile of its candidate and ability to combine it with a range of other drugs as differentiators.