Camizestrant significantly improves progression-free survival in SERENA-6 trial for advanced HR-positive breast cancer with ESR1 mutation

A recent interim analysis of the SERENA-6 Phase III trial has revealed promising results for AstraZeneca’s investigational drug camizestrant, which was tested in combination with cyclin-dependent kinase (CDK) 4/6 inhibitors such as palbociclib, ribociclib, or abemaciclib. This combination has shown significant improvement in progression-free survival (PFS) for patients undergoing first-line treatment for hormone receptor (HR)-positive, HER2-negative advanced breast cancer, particularly in cases where tumors have developed an ESR1 mutation.

The SERENA-6 trial is pioneering in its approach by using circulating tumor DNA (ctDNA) to identify early signs of resistance to current endocrine therapies, thereby allowing for a strategic switch in treatment. Patients whose tumors exhibited the ESR1 mutation were switched from an aromatase inhibitor (AI) to camizestrant, while continuing treatment with a CDK4/6 inhibitor. At the point of this interim analysis, secondary endpoints such as time to second disease progression (PFS2) and overall survival (OS) were still immature, though there was an observable trend towards improved PFS2.

This international, double-blind study incorporates a novel design by monitoring ctDNA during routine tumor scan visits to detect emerging endocrine resistance. This allows for preemptive intervention before the disease progresses further. François-Clément Bidard, a leading oncologist and co-principal investigator for the trial, highlighted the urgent need for treatments that can delay disease progression in patients who have developed resistance to standard endocrine-based therapies. This study suggests that camizestrant, in combination with a CDK4/6 inhibitor, could represent a significant advancement in this area.

Susan Galbraith, Executive Vice President of Oncology Haematology R&D at AstraZeneca, emphasized the potential of camizestrant to become a new standard-of-care, providing a well-tolerated treatment option for a substantial subset of breast cancer patients. The safety profile of camizestrant, when used with CDK4/6 inhibitors, was consistent with existing safety data for these medications, showing no new safety concerns.

Globally, around 200,000 patients with HR-positive breast cancer receive first-line treatment with endocrine therapies often combined with CDK4/6 inhibitors. However, resistance to these treatments frequently develops, driven in many cases by mutations in the ESR1 gene. Approximately 30% of patients with endocrine-sensitive HR-positive breast cancer develop such mutations during treatment, underscoring the need for innovative therapeutic strategies.

The SERENA-6 trial enrolled 315 adult patients with HR-positive, HER2-negative advanced breast cancer, all of whom were initially treated with an AI and a CDK4/6 inhibitor. The trial’s primary focus is on progression-free survival, with secondary goals including overall survival and time to second disease progression.

Camizestrant is a next-generation oral selective estrogen receptor degrader (SERD), being evaluated in several clinical trials for its efficacy and safety in HR-positive breast cancer treatment. Earlier trials have demonstrated its ability to offer progression-free survival benefits over Faslodex, regardless of ESR1 mutation status.

This study forms part of AstraZeneca's broader initiative to transform breast cancer treatment by developing new therapies tailored to various genetic and molecular profiles of the disease. The company’s robust research efforts aim to address unmet needs in breast cancer management, with the ambitious goal of eventually eliminating breast cancer as a cause of death.