AstraZeneca’s experimental breast cancer drug Etcamah (camizestrant) has failed to meet the primary endpoint in a major Phase III trial, dealing a setback to the company’s efforts to expand the drug’s use in earlier lines of treatment.

 

The SERENA-4 trial did not meet its primary endpoint of progression-free survival (PFS) in patients with estrogen receptor (ER)-positive, HER2-negative advanced breast cancer who had not previously received systemic treatment for advanced disease. However, AstraZeneca said a numerical improvement in PFS was observed with Etcamah in combination with palbociclib, a cyclin-dependent kinase (CDK) 4/6 inhibitor.

 

The trial compared the Etcamah-palbociclib combination with an aromatase inhibitor, anastrozole, combined with palbociclib, in the upfront first-line treatment setting.

 

Susan Galbraith, Executive Vice President, Oncology Haematology R&D, AstraZeneca, said: “Whilst we are disappointed by the SERENA-4 outcome, it sharpens our focus on maximising the number of patients who can benefit from Etcamah today based on SERENA-6 and reinforces the importance of ESR1 testing for patients on first-line therapy. 

 

"Early breast cancer represents an important opportunity, and we remain confident in the long-term potential of Etcamah in the early setting as we advance our broader programme.”

 

Despite the efficacy setback, AstraZeneca reported no new safety concerns. The safety profile of Etcamah combined with palbociclib was consistent with the known safety profiles of the individual medicines.

 

The company said detailed SERENA-4 data will be shared in due course.

 

Etcamah has already secured approvals in the US, EU, Japan and several other countries when used with a CDK4/6 inhibitor—palbociclib, ribociclib or abemaciclib—for adults with hormone receptor (HR)-positive, or ER-positive, HER2-negative locally advanced or metastatic breast cancer where an ESR1 mutation is detected or emerges during first-line endocrine-based therapy.

 

Those approvals are based on results from AstraZeneca’s SERENA-6 Phase III trial.

 

The company is now turning its attention to the drug’s potential in early breast cancer. AstraZeneca is evaluating Etcamah in what it describes as the most comprehensive oral selective estrogen receptor degrader (SERD) development programme in early breast cancer.

 

The programme includes the Phase III CAMBRIA-1 and CAMBRIA-2 trials, which together involve approximately 10,000 patients. The studies are assessing Etcamah as a monotherapy, in combination with CDK4/6 inhibitors and following CDK4/6 inhibitor treatment in patients with HR-positive, HER2-negative breast cancer at intermediate or high risk of recurrence.

 

The latest result puts greater focus on these ongoing trials as AstraZeneca seeks to establish Etcamah’s long-term role beyond its current use in patients with ESR1-mutated advanced disease.