Recently published data from a planned interim analysis of the global, double-blind, randomized SERENA-6 phase III trial yielded positive high-level results, which revealed that the investigational, potent, next-generation oral selective estrogen receptor degrader (SERD) and complete ER antagonist, camizestrant, when used in combination with a cyclin-dependent kinase (CDK) 4/6 inhibitor (palbociclib, ribociclib, or abemaciclib), demonstrated a highly statistically significant and clinically meaningful improvement in the primary end point of progression-free survival (PFS).
About the SERENA-6 Phase III Trial
This trial is the first global, double-blind, registrational phase III trial to utilize a circulating tumor DNA–guided methodology to identify the emergence of endocrine resistance and inform a switch in therapy before disease progression.
Researchers assessed switching to the camizestrant combination compared with continuing standard-of-care treatment with an aromatase inhibitor (anastrozole or letrozole) alongside a CDK4/6 inhibitor for first-line therapy in patients with hormone receptor (HR)–positive, HER2-negative advanced breast cancer with tumors that have an emergent ESR1 mutation.
Camizestrant is the first and only next-generation oral SERD and complete ER antagonist to demonstrate first-line benefit in combination with FDA-approved CDK4/6 inhibitors.
At the time of this interim analysis, the key secondary end points of time to second disease progression (PFS2) and overall survival were still immature; however, the camizestrant combination showed a trend toward improvement in PFS2. The trial will proceed as planned to evaluate the key secondary end points further.
In a press release from Astra Zeneca, François-Clément Bidard, MD, PhD, professor of medical oncology at the Institute Curie & UVSQ/Université Paris-Saclay, France, and co-principal investigator for the trial, stated, “Patients have an urgent need for new treatments that delay disease progression on 1st-line endocrine-based therapies. 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 1st-line treatment, representing an important step forward for patients, and a potential shift in clinical practice.”
Susan Galbraith, executive vice president, Oncology Hematology R&D, AstraZeneca, stated, “These impressive results demonstrate the versatility of camizestrant in combination with all the widely approved CDK4/6 inhibitors to provide a well-tolerated new potential treatment option in the first-line setting for the one in three patients with HR-positive, HER2-negative advanced breast cancer whose tumours develop ESR1 mutations during treatment with an aromatase inhibitor in combination with a CDK4/6 inhibitor.”
She added, “This critical read-out moves us one step closer to realising the potential of camizestrant to become a new standard-of-care as we look to shift the treatment paradigm and establish this new endocrine therapy backbone in HR-positive breast cancer.”
Data from SERENA-6 indicated that the safety profile of camizestrant in combination with palbociclib, ribociclib, or abemaciclib was consistent with the established safety profile of each agent. Furthermore, no new safety concerns were identified, and the discontinuation rates were infrequent and comparable in both arms.
Data will be presented at an upcoming medical conference and shared with global regulatory authorities.
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