On September 11, 2026 Astrazeneca reported 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), however a numerical improvement was observed in the upfront 1st-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 an aromatase inhibitor (anastrozole) in combination with palbociclib.
Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:
Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing
Schedule Your 30 min Free Demo!
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."
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. Data will be shared in due course.
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 (or ER-positive), HER2-negative locally advanced or metastatic breast cancer upon detection or emergence of ESR1 mutation during 1st-line endocrine-based therapy, based on the results from the SERENA-6 Phase III trial.
Etcamah is currently being evaluated in the most comprehensive oral SERD development programme in early breast cancer. Encompassing approximately 10,000 patients, the CAMBRIA-1 and CAMBRIA-2 Phase III trials are designed for patients at both intermediate and high risk of recurrence in the adjuvant setting, evaluating Etcamah as a monotherapy, in combination with CDK4/6 inhibitors and following CDK4/6 inhibitor treatment to address areas of unmet need in HR-positive, HER2-negative breast cancer.
Notes
ER-positive breast cancer
Breast cancer is the second most common cancer and one of the leading causes of cancer-related deaths worldwide.1 More than two million patients were diagnosed with breast cancer in 2024, with more than 690,000 deaths globally.1 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.2
HR-positive breast cancer, characterised by the expression of estrogen or progesterone receptors, or both, is the most common subtype of breast cancer with 70% of tumours considered HR-positive and HER2-negative.2 ERs often drive the growth of HR-positive breast cancer cells.3 More than 97% of HR-positive breast cancer tumours are ER-positive.4,5
SERENA-4
SERENA-4 is a Phase III, double-blind, randomised trial evaluating the efficacy and safety of camizestrant in combination with palbociclib, a CDK4/6 inhibitor, versus treatment with an aromatase inhibitor (AI) (anastrozole) in combination with palbociclib in patients with ER-positive, HER2-negative advanced breast cancer (patients with either locally advanced disease, or metastatic disease).
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 (AI or tamoxifen), and at least 12 months had elapsed since the last dose of adjuvant AI therapy without disease progression on treatment.
The primary endpoint of the SERENA-4 trial is PFS as assessed by investigator, with secondary endpoints including OS, PFS2, and health-related quality of life (HRQOL).
Etcamah
Etcamah is a potent, next-generation oral selective estrogen receptor degrader (SERD) and complete ER antagonist, administered orally, once daily. The recommended dose of Etcamah in combination with a CDK4/6 inhibitor is 75mg.
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 HR-positive (or ER-positive), HER2-negative locally advanced or metastatic breast cancer upon detection or emergence of ESR1 mutation during 1st-line endocrine-based therapy, based on the results from the SERENA-6 Phase III trial.
The broad, robust and innovative Etcamah clinical development programme, including the CAMBRIA-1 and CAMBRIA-2 Phase III trials, is evaluating the safety and efficacy of Etcamah when used as a monotherapy or in combination with CDK4/6 inhibitors to address a number of areas of unmet need in HR-positive, HER2-negative breast cancer.
(Press release, AstraZeneca, SEP 11, 2026, View Source [SID1234670777])