AstraZeneca has released positive data from the SERENA-6 Phase III trial, which assessed camizestrant when used in combination with CDK4/6 inhibitors for the first-line treatment of HR-positive, HER2-negative advanced breast cancer. The trial saw strong progression-free survival (PFS) improvement when patients switched to camizestrant upon the identification of an ESR1 mutation, as compared to continuing therapy with an aromatase inhibitor (AI) and a CDK4/6 inhibitor.

Key Highlights:
SERENA-6 Trial Demonstrates Improved Progression-Free Survival (PFS)

• Patients who changed to camizestrant with a CDK4/6 inhibitor (palbociclib, ribociclib, or abemaciclib) demonstrated a very significant and clinically relevant improvement in PFS.

• The trial employed a circulating tumor DNA (ctDNA)-directed strategy to identify early the development of endocrine resistance.

• Secondary endpoints like time to second disease progression (PFS2) and overall survival (OS) were favorable, with the trial ongoing to evaluate these endpoints further.

First Global Trial to Utilize a ctDNA-Guided Strategy for Switching Endocrine Therapy

• SERENA-6 is the first worldwide, double-blind, Phase III trial to use ctDNA monitoring during standard tumor scan visits.

• This new strategy enabled patients to switch treatment before disease progression upon identifying an ESR1 mutation, a primary cause of endocrine resistance.

Clinical Impact: Expert Insights

• Prof. François-Clément Bidard, Institut Curie & UVSQ/Université Paris-Saclay:

“Patients need new treatments that delay disease progression. SERENA-6 results show that switching to camizestrant after detecting an ESR1 mutation prolongs the benefit of first-line therapy and could shift clinical practice.”

• Susan Galbraith, EVP, Oncology R&D, AstraZeneca:

“These impressive results reinforce camizestrant’s potential as a new standard-of-care option in HR-positive breast cancer. The trial demonstrates the ability to extend treatment benefits by proactively addressing ESR1 mutations before progression.”Safety Profile and Treatment Implications

• Camizestrant had a well-tolerated safety profile with no new safety issues noted.

• Discontinuations were low and in line with those for usual endocrine therapy plus CDK4/6 inhibitors.

Future Steps and Clinical Implications:

• Results will be presented at a future medical conference and reported to worldwide regulatory agencies for possible approvals.

• HR-positive, HER2-negative breast cancer represents about 70% of all breast cancers, and the development of ESR1 mutations is a significant challenge to disease treatment.

• AstraZeneca is currently working on next-generation endocrine treatments to overcome resistance to CDK4/6 inhibitors and enhance patient survival.

The SERENA-6 trial results support camizestrant's ability to recast treatment of HR-positive, HER2-negative breast cancer as a means to intervene earlier on endocrine resistance and prolong time to disease progression. With potential approval, camizestrant may become an additional first-line standard-of-care for patients presenting with emergent ESR1 mutations.