AstraZeneca breast cancer combo misses Phase III goal

Rhea-AI Filing Summary

AstraZeneca PLC (AZN) reported that the SERENA-4 Phase III trial of its oral SERD Etcamah (camizestrant) plus palbociclib in 1st-line treatment of ER-positive, HER2-negative advanced breast cancer did not meet its primary endpoint of progression-free survival versus anastrozole plus palbociclib, although a numerical improvement was seen.

The safety profile of Etcamah with palbociclib was consistent with known profiles and no new safety concerns were identified. Etcamah remains approved in multiple major markets for ESR1-mutated HR-positive, HER2-negative advanced breast cancer based on SERENA-6, and is being further studied in large CAMBRIA-1 and CAMBRIA-2 Phase III trials in early breast cancer.

Positive

• None.

Negative

• SERENA-4 Phase III setback: Etcamah plus palbociclib in 1st-line ER-positive, HER2-negative advanced breast cancer failed to achieve a statistically significant improvement in progression-free survival versus anastrozole plus palbociclib, limiting near-term prospects for label expansion in this broad frontline setting.

Key Figures

SERENA-4 enrollment: 1,371 patients CAMBRIA programme size: Approximately 10,000 patients Global breast cancer incidence: More than 2,000,000 cases +4 more

7 metrics

SERENA-4 enrollment 1,371 patients Adults with ER-positive, HER2-negative advanced breast cancer in the Phase III SERENA-4 trial

CAMBRIA programme size Approximately 10,000 patients Patients enrolled across CAMBRIA-1 and CAMBRIA-2 Phase III trials in early breast cancer

Global breast cancer incidence More than 2,000,000 cases Estimated number of patients diagnosed with breast cancer worldwide in 2024

Global breast cancer deaths More than 690,000 deaths Estimated worldwide breast cancer deaths in 2024

HR-positive, HER2-negative share 70% Proportion of breast cancer tumours considered HR-positive and HER2-negative

ER-positive within HR-positive More than 97% Share of HR-positive breast cancer tumours that are ER-positive

Etcamah dose 75 mg Recommended once-daily dose of Etcamah in combination with a CDK4/6 inhibitor

Key Terms

progression-free survival, selective estrogen receptor degrader (SERD), CDK4/6 inhibitor, ESR1 mutation, +2 more

6 terms

progression-free survival medical

"did not meet the primary endpoint of progression-free survival (PFS)"

Progression-free survival is the length of time during and after a treatment that a patient's disease does not get worse, measured from the start of treatment until the disease shows measurable signs of progression or the patient dies. Investors care because longer progression-free survival in clinical trials often signals that a drug is effective, improving chances of regulatory approval, market adoption, and revenue potential—think of it as a stopwatch showing how long a therapy can keep the illness at bay.

selective estrogen receptor degrader (SERD) medical

"Etcamah is a potent, next-generation oral selective estrogen receptor degrader"

CDK4/6 inhibitor medical

"in combination with palbociclib, a CDK4/6 inhibitor"

A CDK4/6 inhibitor is a type of cancer drug that blocks two proteins (CDK4 and CDK6) that tell cells to divide, effectively slowing or stopping the growth of tumors. Think of it as cutting power to a photocopier that keeps making cancer cells; that control can shrink tumors or delay progression. For investors, these drugs matter because clinical trial results, regulatory approvals, patent life, safety issues and competition directly affect sales potential and company value.

ESR1 mutation medical

"upon detection or emergence of ESR1 mutation during 1st-line endocrine-based therapy"

An ESR1 mutation is a change in the gene that makes the estrogen receptor, a protein that acts like a lock on certain cells; when altered, that lock can behave differently. For investors, these mutations matter because they can make hormone drugs less effective or change which treatments and tests are needed, much like a changed lock driving demand for new keys and locksmith services — affecting drug sales, clinical trial success, and the market for diagnostics and follow‑on therapies.

adjuvant setting medical

"patients at both intermediate and high risk of recurrence in the adjuvant setting"

Adjuvant setting describes giving a medical treatment after a main therapy (most often after surgery) to lower the chance that a disease will return; think of it as applying a follow-up guard to catch any remaining cells the primary treatment missed. For investors this matters because success in the adjuvant setting can greatly expand the number of patients eligible for a drug, extend treatment durations, and change regulatory and commercial value compared with use only in later-stage or salvage care.

health-related quality of life (HRQOL) medical

"secondary endpoints including OS, PFS2, and health-related quality of life (HRQOL)"

A measure of how a person’s health affects their everyday functioning, wellbeing and ability to work or enjoy life, typically captured by patient surveys that cover physical, mental and social aspects. Investors use HRQOL to judge a treatment’s real-world value and market potential—similar to measuring customer satisfaction and return-to-normal life—because better patient outcomes can drive demand, pricing, reimbursement and long-term cost forecasts.

FAQ

AI-generated questions and answers. How Rhea-AI works. Not financial advice.

What did AstraZeneca (AZN) announce about the SERENA-4 Phase III trial?

AstraZeneca announced that the SERENA-4 Phase III trial of Etcamah plus palbociclib in 1st-line ER-positive, HER2-negative advanced breast cancer did not meet its primary endpoint of progression-free survival versus anastrozole plus palbociclib, although a numerical improvement was observed.

Does the SERENA-4 outcome affect the existing approval of Etcamah for AZN?

No change to current approval is reported. Etcamah with a CDK4/6 inhibitor is already approved in the US, EU, Japan and other countries for HR-positive, HER2-negative advanced breast cancer upon emergence of an ESR1 mutation, based on the SERENA-6 Phase III trial.

What was the primary endpoint in AstraZeneca’s SERENA-4 trial of Etcamah?

The primary endpoint in SERENA-4 was progression-free survival (PFS) as assessed by the investigator. The Etcamah plus palbociclib arm showed a numerical improvement in PFS but did not achieve a statistically significant benefit versus anastrozole plus palbociclib.

How many patients were enrolled in the SERENA-4 Phase III trial reported by AZN?

The SERENA-4 Phase III trial enrolled 1,371 adult patients with ER-positive, HER2-negative advanced breast cancer, including newly diagnosed Stage IV de novo or recurrent disease patients who had not received systemic treatment for metastatic disease.

Were any new safety concerns identified with Etcamah in SERENA-4 for AstraZeneca (AZN)?

No. The safety profile of Etcamah plus palbociclib in SERENA-4 was reported as consistent with the known safety profile of each medicine, and no new safety concerns were identified. Detailed data will be shared later.

What other major trials of Etcamah is AstraZeneca (AZN) running?

AstraZeneca is running the CAMBRIA-1 and CAMBRIA-2 Phase III trials in early breast cancer, encompassing about 10,000 patients. These evaluate Etcamah as monotherapy, with CDK4/6 inhibitors and after CDK4/6 treatment in HR-positive, HER2-negative disease.

What is the recommended dose of Etcamah in combination with CDK4/6 inhibitors?

The recommended dose of Etcamah when used in combination with a CDK4/6 inhibitor is 75 mg once daily, as stated in AstraZeneca’s disclosure.

AI-generated analysis. How Rhea-AI works. Not financial advice.

Form 6-K: How Foreign Companies Report to the SEC →

See more from StockTitan in Google Search and AI answers. Adds StockTitan as a preferred source · opens Google

Add on Google Not now

Available on EDGAR 09/14/2026 - 07:37 AM Accepted by SEC EDGAR 09/14/2026 - 07:36 AM Learn about SEC filing dates

FORM 6-K

SECURITIES AND EXCHANGE COMMISSION

Washington, D.C. 20549

Report of Foreign Issuer

Pursuant to Rule 13a-16 or 15d-16 of

the Securities Exchange Act of 1934

For the month of September 2026 

Commission File Number: 001-11960

AstraZeneca PLC

1 Francis Crick Avenue

Cambridge Biomedical Campus

Cambridge CB2 0AA

United Kingdom

Indicate by check mark whether the registrant files or will file annual reports under cover of Form 20-F or Form 40-F.

Form 20-F X Form 40-F __

Indicate by check mark if the registrant is submitting the Form 6-K in paper as permitted by Regulation S-T Rule 101(b)(1):

Indicate by check mark if the registrant is submitting the Form 6-K in paper as permitted by Regulation S-T Rule 101(b)(7): ______

Indicate by check mark whether the registrant by furnishing the information contained in this Form is also thereby furnishing the information to the Commission pursuant to Rule 12g3-2(b) under the Securities Exchange Act of 1934.

Yes __ No X

If “Yes” is marked, indicate below the file number assigned to the Registrant in connection with Rule 12g3-2(b): 82-_____________

AstraZeneca PLC

INDEX TO EXHIBITS

1.

Update on SERENA-4 Phase III trial

This announcement contains inside information

14 September 2026

Update on SERENA-4 Phase III trial of Etcamah in combination with

palbociclib in upfront 1st-line advanced ER-positive breast cancer

SERENA-4 trial did not meet primary objective of statistically significant improvement in progression-free survival, however a numerical improvement was observed

Etcamah is the only oral SERD to demonstrate benefit in 1st-line setting and is approved for patients with an emergent ESR1 tumour mutation based on SERENA-6

The SERENA-4 Phase III trial of AstraZeneca's 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.

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. 

AstraZeneca in breast cancer

Driven by a growing understanding of breast cancer biology, AstraZeneca is challenging, and redefining, the current clinical paradigm for how breast cancer is classified and treated to deliver even more effective treatments to patients in need - with the bold ambition to one day eliminate breast cancer as a cause of death.

AstraZeneca has a comprehensive portfolio of approved and promising compounds in development that leverage different mechanisms of action to address the biologically diverse breast cancer tumour environment. 

With Enhertu (trastuzumab deruxtecan), a HER2-directed antibody drug conjugate (ADC), AstraZeneca and Daiichi Sankyo are aiming to improve outcomes in previously treated HER2-positive, HER2-low and HER2-ultralow metastatic breast cancer and are exploring its potential in earlier lines of treatment and in new breast cancer settings. 

In HR-positive breast cancer, AstraZeneca continues to improve outcomes with foundational medicines Faslodex (fulvestrant) and Zoladex (goserelin) and aims to reshape the HR-positive space with first-in-class AKT inhibitor, Truqap (capivasertib), the TROP-2-directed ADC, Datroway (datopotamab deruxtecan) and next-generation oral SERD, Etcamah.

PARP inhibitor Lynparza (olaparib) is a targeted treatment option that has been studied in early and metastatic breast cancer patients with an inherited BRCA mutation. AstraZeneca with MSD (Merck & Co., Inc. in the US and Canada) continue to research Lynparza in these settings. AstraZeneca is also exploring the potential of saruparib, a potent and selective inhibitor of PARP1, in combination with Etcamah or endocrine therapy in BRCA-mutated, HR-positive, HER2-negative advanced breast cancer. 

To bring much-needed treatment options to patients with triple-negative breast cancer, an aggressive form of breast cancer, AstraZeneca is collaborating with Daiichi Sankyo to evaluate the potential of Datroway alone and in combination with immunotherapy Imfinzi (durvalumab).

AstraZeneca in oncology

AstraZeneca is leading a revolution in oncology with the ambition to provide cures for cancer in every form, following the science to understand cancer and all its complexities to discover, develop and deliver life-changing medicines to patients.  

The Company's focus is on some of the most challenging cancers. It is through persistent innovation that AstraZeneca has built one of the most diverse portfolios and pipelines in the industry, with the potential to catalyse changes in the practice of medicine and transform the patient experience.  

AstraZeneca has the vision to redefine cancer care and, one day, eliminate cancer as a cause of death. 

AstraZeneca

AstraZeneca (LSE/STO/NYSE: AZN) is a global, science-led biopharmaceutical company that focuses on the discovery, development, and commercialisation of prescription medicines in Oncology, Rare Disease, and BioPharmaceuticals, including Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca's innovative medicines are sold in more than 125 countries and used by millions of patients worldwide. Please visit astrazeneca.com and follow the Company on Social Media @AstraZeneca.

Contacts

For details on how to contact the Investor Relations Team, please click here. For Media contacts, click here. 

References

1.   Sung H, et al. Global cancer statistics 2024: GLOBOCAN estimates of incidence and mortality worldwide for 34 cancers in 186 countries. CA Cancer J Clin. 2026; DOI: 10.3322/caac.70090.

2.   National Cancer Institute. Cancer Stat facts: Female breast cancer subtypes. Available at: https://seer.cancer.gov/statfacts/html/breast-subtypes.html. Accessed September 2026.

3.   Scabia V, et al. Estrogen receptor positive breast cancers have patient specific hormone sensitivities and rely on progesterone receptor. Nat Commun. 2022; 10.1038/s41467-022-30898-0.

4.   Bae S, et al. Poor prognosis of single hormone receptor positive breast cancer: similar outcome as triple-negative breast cancer. BMC Cancer. 2015; 15:138.

5.   Cserni G, et al. Estrogen Receptor Negative and Progesterone Receptor Positive Breast Carcinomas-How Frequent are they? Pathol. Oncol. Res. 2011; 17:663-668.

Matthew Bowden​

​​Company Secretary​

​​AstraZeneca PLC​

This announcement contains information that AstraZeneca PLC is obliged to make public pursuant to the EU Market Abuse Regulation (596/2014) and the assimilated EU Market Abuse Regulation (596/2014) as it forms part of the law of the United Kingdom by operation of the European Union (Withdrawal) Act 2018. This announcement was submitted for publication, through the agency of the contact person(s) set out above, at 21:15 BST 11 September 2026.

SIGNATURES

Pursuant to the requirements of the Securities Exchange Act of 1934, the Registrant has duly caused this report to be signed on its behalf by the undersigned, thereunto duly authorized.

AstraZeneca PLC

Date: 14 September 2026

By: /s/ Matthew Bowden

Name: Matthew Bowden

Title: Company Secretary