AstraZeneca's SERENA-4 trial misses main goal for Etcamah in first-line breast cancer

AstraZeneca said on September 14, 2026 that its SERENA-4 Phase III trial did not reach its main goal. The trial tested Etcamah (camizestrant) combined with the CDK4/6 inhibitor palbociclib against an aromatase inhibitor combination and did not achieve a statistically significant gain in progression-free survival, though the data trended in favor of the treatment arm.¹ The comparison arm used anastrozole with palbociclib.¹

The study population consisted of previously untreated patients with advanced ER-positive, HER2-negative breast cancer. A total of 1,371 adults took part, all newly diagnosed with either Stage IV de novo disease or disease that had recurred, and none had received prior systemic treatment for metastatic cancer.¹ Those who relapsed after early-stage disease had completed at least 24 months of adjuvant endocrine therapy, with a minimum 12-month gap since their last adjuvant AI dose while remaining progression-free.¹ Investigator-assessed PFS served as the primary measure, while overall survival, PFS2, and quality of life were tracked as secondary outcomes.¹

On safety, the combination's tolerability profile matched what has already been seen for each drug individually, and no unexpected safety signals turned up.¹ The company said fuller data will follow at a later date.¹

Susan Galbraith, the company's oncology R&D head, said the SERENA-4 result was disappointing but strengthens the company's focus on expanding access to Etcamah based on the earlier SERENA-6 trial, along with underscoring the need for ESR1 testing in first-line patients.¹

Separately, Etcamah paired with a CDK4/6 inhibitor (palbociclib, ribociclib, or abemaciclib) already holds approval in the US, EU, Japan and other markets for HR-positive, HER2-negative advanced or metastatic breast cancer once an ESR1 mutation appears during first-line endocrine therapy, based on SERENA-6 findings.¹ The drug is also under study in the CAMBRIA-1 and CAMBRIA-2 Phase III programs, which together involve about 10,000 patients in the early breast cancer setting.¹