Etcamah Misses Primary Endpoint in SERENA-4 Breast Cancer Trial

AstraZeneca (AZN ) said on 11 September 2026 that the SERENA-4 Phase III trial of Etcamah (camizestrant) in combination with palbociclib, a cyclin-dependent kinase (CDK) 4/6 inhibitor, did not meet the primary endpoint of progression-free survival (PFS), although a numerical improvement was observed, in the upfront first-line treatment of patients with estrogen receptor (ER)-positive, HER2-negative advanced breast cancer who have not received any systemic treatment for advanced disease. The trial evaluated the Etcamah combination versus treatment with the aromatase inhibitor anastrozole in combination with palbociclib.

The company announcement was marked as containing inside information and was submitted for publication at 21:15 BST on 11 September 2026 pursuant to the EU Market Abuse Regulation.

Susan Galbraith, Executive Vice President of Oncology Haematology R&D at 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.”

AstraZeneca stated that the safety profile of Etcamah in combination with palbociclib in SERENA-4 was consistent with the known safety profile of each medicine, with no new safety concerns identified. The company said the data will be shared in due course.

SERENA-4 Trial Design

SERENA-4 is a Phase III, double-blind, randomised trial evaluating the efficacy and safety of camizestrant in combination with palbociclib versus anastrozole in combination with palbociclib in patients with ER-positive, HER2-negative locally advanced or metastatic breast cancer. The global trial enrolled 1,371 adult patients newly diagnosed with Stage IV de novo or recurrent disease who had not received any systemic treatment for metastatic disease. Patients with recurrence from early-stage disease had received at least 24 months of standard adjuvant endocrine therapy with an aromatase inhibitor or tamoxifen, and at least 12 months had elapsed since the last dose of adjuvant aromatase inhibitor therapy without disease progression on treatment.

The primary endpoint of SERENA-4 is PFS as assessed by the investigator, with secondary endpoints including overall survival (OS), second progression-free survival (PFS2) and health-related quality of life.

Approved Use and the SERENA-6 Evidence Base

Etcamah in combination with a CDK4/6 inhibitor (palbociclib, ribociclib or abemaciclib) is approved in the US, EU, Japan and several other countries for the treatment of adult patients with hormone receptor (HR)-positive, HER2-negative locally advanced or metastatic breast cancer upon detection or emergence of an ESR1 mutation during first-line endocrine-based therapy, based on the results of the SERENA-6 Phase III trial. AstraZeneca describes Etcamah as the only oral selective estrogen receptor degrader (SERD) to demonstrate benefit in the first-line setting.

SERENA-6 enrolled 315 adult patients with HR-positive, HER2-negative advanced breast cancer who were undergoing first-line treatment with an aromatase inhibitor (anastrozole or letrozole) in combination with a CDK4/6 inhibitor. According to the company, it is the first global registrational Phase III trial to use a circulating tumour DNA (ctDNA)-guided approach to detect the emergence of endocrine resistance and inform a switch in therapy before disease progression. The design used ctDNA monitoring via a blood test at the time of routine tumour scans every two to three months; following detection of an ESR1 mutation without disease progression, a patient’s endocrine therapy was switched from the aromatase inhibitor to camizestrant while treatment with the same CDK4/6 inhibitor continued.

In updated SERENA-6 results presented at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago on 2 June 2026, the camizestrant combination reduced the risk of disease progression or death by 55% versus an aromatase inhibitor plus a CDK4/6 inhibitor, based on a hazard ratio of 0.45 (95% confidence interval 0.34-0.59; p<0.00001). Median PFS was 16.8 months for the camizestrant combination compared with 9.2 months for the aromatase inhibitor combination, representing a median improvement of 7.6 months.

The June update also reported the final analysis of PFS2, a measure of treatment durability beyond first progression, in which the camizestrant combination reduced the risk of second disease progression or death by 37% (hazard ratio 0.63; 95% confidence interval 0.46-0.86; p=0.00373), with median PFS2 of 25.7 months versus 19.1 months. Patients who switched to the camizestrant combination had a median 99% reduction in total ctDNA by week 8, with 51% achieving total ctDNA clearance, compared with a median 64% increase in total ctDNA and 1.9% clearance among patients who remained on the aromatase inhibitor combination. Data for the key secondary endpoint of OS showed a numerical trend favouring the camizestrant combination (hazard ratio 0.87; 95% confidence interval 0.57-1.30) at 30% maturity, and the trial will continue to final analysis of OS.

The SERENA-6 primary results were first presented at the 2025 ASCO meeting and simultaneously published in The New England Journal of Medicine. Earlier in the development programme, the SERENA-2 Phase II trial demonstrated a statistically significant and clinically meaningful improvement in PFS for camizestrant versus Faslodex (fulvestrant) in patients with ER-positive locally advanced or metastatic breast cancer previously treated with endocrine therapy, and the SERENA-1 Phase I trial evaluated camizestrant alone and in combination with the CDK4/6 inhibitors palbociclib, ribociclib and abemaciclib.

Beyond the metastatic setting, Etcamah is being evaluated in the CAMBRIA-1 and CAMBRIA-2 Phase III trials in early breast cancer. Encompassing approximately 10,000 patients at both intermediate and high risk of recurrence, the adjuvant trials are evaluating Etcamah as a monotherapy, in combination with CDK4/6 inhibitors and following CDK4/6 inhibitor treatment. AstraZeneca describes the programme as the most comprehensive oral SERD development programme in early breast cancer.

Etcamah is a next-generation oral selective estrogen receptor degrader and complete ER antagonist, administered orally once daily. The recommended dose of Etcamah in combination with a CDK4/6 inhibitor is 75mg.

Breast cancer is the second most common cancer and one of the leading causes of cancer-related deaths worldwide, according to figures cited in the announcement. More than two million patients were diagnosed with breast cancer in 2024, with more than 690,000 deaths globally. HR-positive breast cancer, characterised by the expression of estrogen or progesterone receptors, or both, is the most common subtype, with 70% of tumours considered HR-positive and HER2-negative, and more than 97% of HR-positive tumours are ER-positive. While survival rates are high for those diagnosed with early breast cancer, only about 30% of patients diagnosed with or who progress to metastatic disease are expected to live five years following diagnosis.