NEW YORK – AstraZeneca on Wednesday said it will share with regulators interim data from a Phase III trial showing that camizestrant plus a CDK4/6 inhibitor bested standard treatment with aromatase and CDK4/6 inhibitors as a first-line option in advanced hormone receptor (HR)-positive breast cancers harboring ESR1 mutations.
Camizestrant, a complete estrogen receptor antagonist, inhibits estrogen receptor transcriptional activity and degrades the receptor, whereas aromatase inhibitors like anastrozole and letrozole leave the receptor in place but reduce the production of estrogen, which in turn decreases ligand-driven transcriptional activity. AstraZeneca believes camizestrant's dual mechanism will give it an edge over aromatase inhibitors when combined with CDK4/6 inhibition in patients with ESR1-mutated, HR-positive, HER2-negative advanced breast cancer.
In the SERENA-6 trial, researchers are comparing treatment with camizestrant and a CDK4/6 inhibitor to an aromatase inhibitor plus a CDK4/6 inhibitor in about 315 patients. To be eligible for the trial, patients must not have progressed on standard therapy with an aromatase inhibitor and any one of three approved CDK4/6 inhibitors: Pfizer's Ibrance (palbociclib), Novartis' Kisqali (ribociclib), or Eli Lilly's Verzenio (abemaciclib). Patients continue to receive the same CDK4/6 inhibitor but will receive either an aromatase inhibitor or camizestrant with a placebo, depending on the study arm to which they're randomized.
An interim analysis of this study has shown that patients on camizestrant combination therapy had a statistically significant and clinically meaningful improvement in progression-free survival compared to patients on standard-of-care therapy with an aromatase inhibitor and a CDK4/6 inhibitor. Results on secondary endpoints such as time-to-second disease progression and overall survival were not mature at the time of the interim analysis.
"The results from SERENA-6 show that switching from an aromatase inhibitor to camizestrant in combination with any of the three CDK4/6 inhibitors after emergence of an ESR1 mutation delays progression of disease and extends the benefit of first-line treatment, representing an important step forward for patients and a potential shift in clinical practice," François-Clément Bidard, a professor of medical oncology at Institut Curie & UVSQ/Université Paris-Saclay, France, and co-principal investigator for the trial, said in a statement.
AstraZeneca said it will share data from the interim analysis at an upcoming medical conference and discuss it with regulators around the world.
If approved, camizestrant would compete with Menarini Group's SERD Orserdu (elacestrant) and investigational therapies, including Eli Lilly's SERD imlunestrant and Olema Oncology's complete estrogen receptor antagonist palazestrant. Menarini is evaluating Orserdu in combination with Verzenio in second-line ER-positive advanced breast cancer and has evidence suggesting that the combination appears to have activity in patients regardless of ESR1 status. Lilly recently presented results from a Phase III trial in which imlunestrant plus Verzenio benefited patients with ESR1 mutations and other resistance mechanisms. And Olema Oncology is preparing to launch a Phase III trial of palazestrant following Phase II results demonstrating improved progression-free survival among patients with ESR1-mutant disease.