Doctors leading this study would like to learn about providing cancer treatment/therapies to Nigerian women with breast cancer based on their human epidermal growth factor receptor 2 (HER2) status. This study will focus on the efficacy and safety of anti-HER2 cancer treatment before and after surgery.

Start Date01 Jan 2026

Sponsor / Collaborator

The University of Chicago

NCT06905301

/ Not yet recruitingNot Applicable

Implementation Study to Describe and Compare Retention Rate and Adherence to Adjuvant Therapy With Ribociclib With and Without Usage of Mobile Application in Patients With HR+ HER2-negative Stage II and III Breast Cancer in Real-world Practice

This study is designed to evaluate the effect of using the application on the adherence of patients with luminal HER2- breast cancer (BC) stage II-III to adjuvant therapy with ribociclib in combination with an aromatase inhibitor (AI). The purpose of the app is to increase adherence to treatment by informing patients about the risks of relapse and adverse event prevention and treatment.

Start Date31 Jul 2025

Sponsor / Collaborator

Novartis Pharmaceuticals Canada, Inc.

NCT06930859

/ Not yet recruitingNot Applicable

Non-interventional Study to Assess the Effectiveness and Safety of Ribociclib in the Adjuvant Therapy of Hormone Receptor Positive (HR+) HER2-negative Stage II and III Breast Cancer in Real Clinical Practice in Russia

This prospective, observational, multicenter study aims at evaluating the efficacy of adjuvant ribociclib in combination with hormone therapy (aromatase inhibitor ± GnRH aginost) in various subgroups of patients with HR+HER2- stage II-III breast cancer in real clinical practice in Russia. Subgroup division will be based on the tumor grade, lymph node involvement, and the response to test hormone therapy. The study will consist of two cohorts: a prospective one with patients receiving adjuvant therapy with ribociclib combined with Aromatase inhibitors (AI), and a retrospective one with patients receiving adjuvant therapy with AI alone. Thus, both primary data collection and secondary use of data will be organized.

Start Date31 Jul 2025

Sponsor / Collaborator

Novartis Pharmaceuticals Canada, Inc.

100 Clinical Results associated with Letrozole

100 Translational Medicine associated with Letrozole

100 Patents (Medical) associated with Letrozole

6,175

Literatures (Medical) associated with Letrozole

31 Dec 2025·GYNECOLOGICAL ENDOCRINOLOGY

Study on the mechanism of action of berberine combined with Jianpi Yishen Huazhuo formulation in treating obese polycystic ovary syndrome by activating PI3K/AKT signaling pathway

Article

Author: Feng, Yahong ; Du, Cuizhong ; Liang, Lijun ; Ye, Gaxi ; Ahmad, Aqsa ; Ji, Dejiang ; Zhang, Xiaojing ; Zhang, Yan

OBJECTIVES:

This study aims to investigate the effects and potential mechanisms of berberine in conjunction with Jianpi Yishen Huazhuo formulation (JPYSHZF) on obese rats that serve as a model for polycystic ovary syndrome (PCOS).

METHODS:

Letrozole combined with high-fat diet (HFD) was used to establish an overweight PCOS rat model. After successful modeling, each intervention group was monitored for 28 d. An oral glucose tolerance test (OGTT) is performed to assess glucose metabolism. Enzyme-linked immunosorbent assay (ELISA) was used to determine the levels of sex hormones and serum levels of gastrointestinal hormones in rats. Biochemical analyzers were used to assess blood lipid levels. The protein expression levels of p38, PI3K, GLUT4, and AKT in ovarian tissue were demonstrated using Western Blotting (WB). Real-time fluorescence quantitative PCR (RT-qPCR) was used to measure the mRNA expression levels of p38, PI3K, GLUT4 and AKT in the same tissue. The morphological changes of ovarian tissue were observed using Hematoxylin-eosin (HE).

RESULTS:

Treatment with berberine in conjunction with JPYSHZF has been shown to reduce serum testosterone T and luteinizing hormone (LH) levels while increasing serum follicle-stimulating hormone (FSH) and E2 levels. This combination therapy also decreases the LH/FSH ratio and ameliorates polycystic ovary-like pathological changes in the ovaries of rats with PCOS. Additionally, this treatment decreases serum TC, TG, and LDL-c levels while increasing HDL-c levels. It also reduces levels of GLU and Ghrelin while enhancing levels of CCK, PYY, and GLP-1. Furthermore, the relative 6 of PI3K and AKT proteins, as well as the mRNA levels of PI3K, GLUT4, and AKT, were found to be increased.

CONCLUSIONS:

Berberine combined with JPYSHZF can improve the sex hormone levels, ovarian function, glucose and lipid metabolism levels, and gastrointestinal hormone levels in obese PCOS rats by activating the PI3K/AKT signaling pathway, thereby playing a role in treating obese PCOS.

31 Dec 2025·GYNECOLOGICAL ENDOCRINOLOGY

Animal experiments and network pharmacology to explore the anti-inflammatory mechanism of dapagliflozin in the treatment of polycystic ovary syndrome

Article

Author: Zhang, Zhen ; Bai, He ; Liu, Yong ; Li, Luxin ; Guan, Huilin ; Song, Xueqing ; Yong, Zihao ; Guo, Xiaomeng ; Wang, Chunhua

BACKGROUND:

Polycystic ovary syndrome (PCOS) is a common endocrine and metabolic disorder associated with chronic low-grade inflammation of the ovary. Sodium glucose co-transporter 2 (SGLT2) inhibitors are a class of antidiabetic drugs that can reduce the weight and hyperglycemia of type 2 diabetes patients. Dapagliflozin is a highly selective, orally active and reversible inhibitor of the human SGLT2. However, the role of dapagliflozin in regulating PCOS remains unclear.

METHODS:

In this study, 24 six-week-old female Sprague Dawley (SD) rats were randomly divided into control, letrozole, and letrozole + dapagliflozin groups. PCOS model rats were produced by gavage administration of letrozole for 21 days. The intervention was conducted after the gavage administration of dapagliflozin for 14 days to evaluate the estrous cycle and ovarian imaging changes of the rats in each group. We observed changes in the weight, ovarian weight, and ovarian morphology of the rats in each group. Pathological changes in the ovaries were examined by H&E staining, changes in ovarian tissue cell apoptosis were identified using TdT-mediated dUTP Nick-End Labeling (TUNEL) staining, and changes in inflammation-related factors were detected using immunohistochemistry and Western blotting analysis. Network pharmacology was used to predict the inflammatory targets and pathways affected by dapagliflozin in treating PCOS, and the potential interactions between dapagliflozin and inflammation-related target proteins were evaluated through molecular docking.

RESULTS:

Our results demonstrated that dapagliflozin treatment significantly improved PCOS symptoms, recovered ovarian morphology and physiological functions, and reduced the apoptosis of ovarian cells after drug intervention. Dapagliflozin treatment also reduced the levels of pro-inflammatory cytokines such as IL-1β, IL-6, and TNF-α, indicating its anti-inflammatory properties. Furthermore, network pharmacology identified 26 intersecting target genes relevant to inflammation in PCOS, with subsequent molecular docking simulations revealing strong binding affinities of dapagliflozin to key targets, including AKT1 and TP53.

CONCLUSIONS:

These findings suggest that dapagliflozin exerts beneficial effects on PCOS by ameliorating ovarian dysfunction and reducing inflammation. Dapagliflozin represents a promising therapeutic candidate for managing PCOS, warranting further clinical investigation to explore its full potential in treating this multifaceted disorder.

01 Jul 2025·EUROPEAN JOURNAL OF PHARMACOLOGY

Evaluating spironolactone monotherapy against combined treatment with metformin in rat PCOS model

Article

Author: Ganie, Mohd Ashraf ; Shafi, Majid ; Bhat, Javeed Iqbal ; Singh, Hemant ; Hassan, Shabir ; Wani, Imtiyaz Ahmad ; Bashir, Showkeen Muzamil ; Sheikh, Wajid Mohammad ; Ul Haq Shah, Mohd Zahoor ; Nabi, Showkat Ul ; Ali, Sofi Imtiyaz ; Rather, Muzafar Ahmad

Polycystic ovarian syndrome (PCOS) is a common gynecological disorder with multifactorial pathogenic risk factors. Combination therapy with metformin and thiazolidinedione derivatives is frequently used, but its synergistic effects have not been thoroughly evaluated. This study aims to compare the therapeutic efficacy of low-dose spironolactone (LDS) at 0.25 mg/kg for 28 days, metformin at 500 mg/kg for 28 days, and a combination of LDS and metformin, against a letrozole (1 mg/kg/day) and 0.5% carboxymethylcellulose (CMC)-induced PCOS rat model. The study involved five groups of laboratory animals: Group I (Healthy control), Group IIa (Disease control), Group IIb (Metformin), Group IIc (LDS), and Group IId (Metformin + LDS). Therapeutic efficacy was evaluated based on phenotypic, hormonal, and genotypic determinants. Letrozole successfully induced PCOS in the animals, evidenced by elevated levels of Sex Hormone Binding Globulin (SHBG), Follicle Stimulating Hormone (FSH), and progesterone, as well as the presence of multiple ovarian cysts. Hierarchical Cluster Analysis indicated that LDS was superior to metformin and the combination therapy in ameliorating PCOS symptoms. The findings suggest that there is little to no benefit in adding metformin to LDS for the clinical management of PCOS. Although these results are from preclinical studies, further case-controlled, randomized placebo studies on a larger patient sample are necessary to confirm these findings in clinical settings.

173

News (Medical) associated with Letrozole

24 Apr 2025

·www.prnewswire.com

IBRANCE's Market Growth Marks a Significant Step Forward in Metastatic HR+/HER2− Breast Cancer Treatment Landscape | DelveInsight

Since its launch in 2015, it has been prescribed to more than 200,000 patients globally. The drug is currently approved for use in both men and women, expanding its market potential. Despite facing competition from other CDK4/6 inhibitors like Novartis' KISQALI and Eli Lilly's VERZENIO, IBRANCE maintains a strong position in the metastatic setting. LAS VEGAS, April 24, 2025 /PRNewswire/ -- DelveInsight's " IBRANCE Market Size, Forecast, and Market Insight Report" highlights the details around IBRANCE, a CDK4/6 inhibitor. The report provides product descriptions, patent details, and competitor products (marketed and emerging therapies) of IBRANCE. The report also highlights the historical and forecasted sales from 2020 to 2034 segmented into 7MM [the United States, the EU4 (Germany, France, Italy, and Spain), the United Kingdom, and Japan]. Pfizer's IBRANCE (palbociclib) Overview IBRANCE is an oral medication that inhibits CDKs 4 and 6, which are crucial regulators of the cell cycle that drive cellular progression. In the U.S., IBRANCE is approved for treating adult patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced or metastatic breast cancer. It is used in combination with an aromatase inhibitor as a first-line endocrine therapy for postmenopausal women or men or with fulvestrant for patients whose disease has progressed after endocrine treatment. IBRANCE is currently authorized in over 90 countries and has been prescribed to more than 200,000 patients worldwide. Learn more about IBRANCE projected market size for metastatic HR+/HER2− breast cancer @ IBRANCE Market Potential The HR+ HER2- subtype is the most commonly found type of breast cancer, characterized by cancer cells that have estrogen and progesterone receptors but do not overexpress HER2. A patient's journey typically begins with the onset of concerning symptoms, leading to a comprehensive clinical evaluation and various imaging tests. DelveInsight estimates that approximately 211K new cases of HR+/HER2– breast cancer occurred in the US in 2024. CDK4/6 inhibitors currently dominate the first-line treatment market and represent a significant advancement in the management of HR+/HER2-ve breast cancer. The data from large, randomized clinical trials are both strong and consistent. While single-agent endocrine therapies have shown limited benefits in the first and subsequent treatment lines for women with ER-positive metastatic breast cancer (mBC), combination therapies have emerged as a more effective option for many patients. In recent years, the treatment landscape for HR+/HER2−ve breast cancer has been transformed with the introduction of highly active targeted therapies, including CDK4/6 inhibitors, mTOR inhibitors, PARP inhibitors, new oral SERDs, and PI3K inhibitors. These advances have expanded the range of treatment options and improved survival outcomes for these patients. The market for metastatic HR+/HER2− breast cancer in the 7MM is projected to grow during the forecast period (2025–2034) due to the introduction of several novel therapies in the market. Discover more about the metastatic HR+/HER2− breast cancer market in detail @ Metastatic HR+/HER2− Breast Cancer Market Report Emerging Competitors of IBRANCE Some of the drugs in the pipeline include Gedatolisib (Celcuity), ARV-471 (Arvinas and Pfizer), OP-1250 (Olema Pharmaceuticals), KEYTRUDA (Merck), and Rupitasertib (Evexta Bio), among others. In December 2024, Arvinas and Pfizer presented preliminary data from the ongoing Phase 1b portion of the TACTIVE-U sub-study of vepdegestrant in combination with abemaciclib among patients with locally advanced or metastatic ER+/HER2- breast cancer at the San Antonio Breast Cancer Symposium (SABCS) 2024. In December 2024, Olema Pharmaceuticals presented clinical results from the ongoing Phase Ib/II study of palazestrant in combination with ribociclib in patients with ER+/HER2- advanced or metastatic breast cancer at SABCS 2024. To know more about the number of competing drugs in development, visit @ IBRANCE Market Positioning Compared to Other Drugs Key Milestones of IBRANCE In February 2021, Pfizer Inc. announced that the U.S. Patent and Trademark Office (USPTO) has granted a U.S. Patent Term Extension (PTE) certificate for IBRANCE. This extension prolongs the validity of U.S. Patent No. RE47,739 ('739) by over four years, now lasting until March 5, 2027. In April 2019, Pfizer announced that the FDA has approved a supplemental New Drug Application (sNDA) to broaden the uses of IBRANCE in combination with an aromatase inhibitor or fulvestrant, now including men with hormone receptor-positive (HR+), HER2-negative (HER2-) advanced or metastatic breast cancer. In March 2017, Pfizer Inc. revealed that the FDA has approved a supplemental New Drug Application (sNDA) for IBRANCE, its pioneering cyclin-dependent kinase 4/6 (CDK 4/6) inhibitor, following the positive outcomes from the confirmatory Phase 3 trial PALOMA-2. In September 2016, Pfizer Inc. announced that the European Medicines Agency's (EMA) Committee for Medicinal Products for Human Use (CHMP) had issued a positive recommendation for the marketing authorization of IBRANCE® (palbociclib) in the European Union (EU). This recommendation is for its use in treating women with hormone receptor-positive, HER2-negative (HR+/HER2-) locally advanced or metastatic breast cancer. In February 2016, Pfizer announced that the FDA has approved a new indication for IBRANCE 125mg capsules, expanding its use. The approval allows IBRANCE to be used in combination with fulvestrant for the treatment of hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced or metastatic breast cancer in women whose disease has progressed after endocrine therapy. In February 2015, Pfizer announced that the FDA granted accelerated approval for IBRANCE in combination with letrozole to treat postmenopausal women with estrogen receptor-positive, human epidermal growth factor receptor 2-negative (ER+/HER2-) advanced breast cancer as the initial endocrine-based therapy for their metastatic disease. Discover how IBRANCE is shaping the metastatic HR+/HER2− breast cancer treatment landscape @ IBRANCE Drug IBRANCE Market Dynamics IBRANCE is a targeted therapy that has revolutionized the treatment of hormone receptor-positive, HER2-negative breast cancer, particularly in combination with aromatase inhibitors or letrozole. Developed by Pfizer, IBRANCE was one of the first CDK4/6 inhibitors approved by the FDA for metastatic breast cancer, and its approval has significantly changed the treatment landscape. The drug works by inhibiting cyclin-dependent kinases 4 and 6, which are key regulators of the cell cycle, thus preventing cancer cells from proliferating. Its market dynamics have been shaped by the growing demand for targeted therapies, as well as the increasing focus on precision medicine and improved patient outcomes. The global market for IBRANCE has been positively impacted by its proven efficacy in clinical trials and its ability to extend progression-free survival in breast cancer patients. The drug's market dominance is underpinned by its widespread acceptance and adoption by oncologists worldwide. However, competition is intensifying, with other CDK4/6 inhibitors such as VERZENIO (abemaciclib) and KISQALI (ribociclib) entering the market, offering similar benefits but with some distinct clinical profiles. This competitive landscape has led to strategic pricing and marketing strategies by Pfizer, aiming to maintain IBRANCE's market leadership while managing pressures from generic alternatives. Additionally, the evolving reimbursement landscape and regulatory policies around oncology drugs are crucial factors influencing the market dynamics. Health insurers and government healthcare programs often scrutinize the cost-effectiveness of cancer treatments, which can impact the pricing and accessibility of IBRANCE in different markets. Another factor is the rising focus on combination therapies, as IBRANCE is often used in conjunction with other drugs like letrozole, which boosts its efficacy and market potential. The shift toward personalized cancer treatment regimens is expected to continue fueling demand for CDK4/6 inhibitors like IBRANCE, especially in more advanced stages of breast cancer. In terms of geographical markets, IBRANCE has seen significant uptake in North America and Europe, where the healthcare infrastructure supports innovative cancer therapies. However, emerging markets, where the economic barriers to accessing expensive cancer treatments can be higher, present a challenge to the widespread use of IBRANCE. Pfizer's ongoing efforts to expand in these regions, through partnerships and pricing adjustments, will be key to ensuring continued growth in global market share. Overall, the IBRANCE market is poised for steady growth, driven by clinical advancements, increasing breast cancer diagnoses, and the continual push toward more targeted, effective therapies. Dive deeper to get more insight into IBRANCE's strengths & weaknesses relative to competitors @ IBRANCE Market Drug Report Table of Contents Related Reports Metastatic HR+/HER2− Breast Cancer Market Metastatic HR+/HER2− Breast Cancer Market Insights, Epidemiology, and Market Forecast – 2034 report deliver an in-depth understanding of the disease, historical and forecasted epidemiology, as well as the market trends, market drivers, market barriers, and key metastatic HR+/HER2− breast cancer companies, including Merck, Arvinas, Olema Pharmaceuticals, Celcuity, Roche, AstraZeneca, Daiichi Sankyo, Eli Lilly, Sermonix Pharmaceuticals, Genentech, Veru Pharma, DualityBio, BioNtech, Evgen Pharma, Carrick Therapeutics, EQRx, G1 Therapeutics, Immutep, among others. HR+/HER2− Breast Cancer Pipeline HR+/HER2− Breast Cancer Pipeline Insight – 2025 report provides comprehensive insights about the pipeline landscape, pipeline drug profiles, including clinical and non-clinical stage products, and the key HR+/HER2− breast cancer companies, including Regor Therapeuics, Seagen Inc., CytomX Therapeutics, Taizhou EOC Pharma, Chia Tai Tianqing Pharmaceutical Group, AstraZeneca, Daiichi Sankyo, Inc., Tyme, Inc., Seagen Inc., Context Therapeutics, Eisai Inc., Shanghai Hengrui Pharmaceutical Co., Ltd., Jiangsu Simcere Pharmaceutical Co., Kind Pharmaceuticals, Merus N.V., Atossa Therapeutics, Roche, among others. Breast Cancer Market Breast Cancer Market Insights, Epidemiology, and Market Forecast – 2034 report deliver an in-depth understanding of the disease, historical and forecasted epidemiology, market share of the individual therapies, and key breast cancer companies including Veru, Sanofi, Roche, AstraZeneca, Eli Lilly, EQRx, Gilead, Sermonix Pharmaceuticals, Evgen Pharma, Tyme, Genentech, Daiichi Sankyo, among others. Metastatic Breast Cancer Pipeline Metastatic Breast Cancer Pipeline Insight – 2025 report provides comprehensive insights about the pipeline landscape, including clinical and non-clinical stage products, and the key metastatic breast cancer companies, including Roche, RemeGen, SynCore Biotechnology, Allarity Therapeutics, Daiichi Sankyo Company, Jiangsu Alphamab Biopharmaceuticals Co., Ltd, Byondis B.V., Jiangsu Hansoh Pharmaceutical Co., Ltd., Shanghai Miracogen Inc., Ambrx, Inc., Daehwa Pharmaceutical Co., Ltd., Phoenix Molecular Designs, GlycoMimetics Incorporated, Rhizen Pharmaceuticals SA, Menarini Group, Samus Therapeutics, Inc., Hanmi Pharmaceutical Company Limited, Jiangxi Qingfeng Pharmaceutical Co. Ltd., Immutep Limited, Arvinas Inc., G1 Therapeutics, Mirati Therapeutics Inc., Chia Tai Tianqing Pharmaceutical, Shanghai Pharmaceuticals Holding Co., Ltd, Pfizer, OncoTherapy Science, Inc., Eisai Inc., Dizal Pharmaceuticals, Jiangsu Hengrui Medicine Co., Tyme, Inc, Orion Pharma, HiberCell, Inc., Rhizen Pharmaceuticals SA, Hutchison Medipharma Limited, OncoPep Inc., Taizhou Hanzhong biomedical co. LTD, among others. About DelveInsight DelveInsight is a leading Business Consultant and Market Research firm focused exclusively on life sciences. It supports pharma companies by providing comprehensive end-to-end solutions to improve their performance. Get hassle-free access to all the healthcare and pharma market research reports through our subscription-based platform PharmDelve . Contact Us Shruti Thakur [email protected] +14699457679 Logo: SOURCE DelveInsight Business Research, LLP WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

Drug ApprovalPhase 3Phase 1Clinical Result

27 Feb 2025

·www.echemi.com

AstraZeneca's Next-Gen Oral SERD Shows Promising Results in Breast Cancer Trial

On February 26, 2025, AstraZeneca announced positive mid-term results from the Phase III SERENA-6 trial for its oral selective estrogen receptor degrader (SERD) camizestrant. The study demonstrated statistically and clinically significant improvements in progression-free survival (PFS) when combined with CDK4/6 inhibitors such as palbociclib, ribociclib, or abemaciclib. This marks camizestrant as the first and only oral SERD proven to provide first-line treatment benefits when used with approved CDK4/6 inhibitors. The SERENA-6 trial assessed the efficacy and safety of switching to camizestrant in patients with hormone receptor-positive (HR+), HER2-negative advanced breast cancer harboring ESR1 mutations. The study compared the camizestrant combination therapy to the standard care of continuing with aromatase inhibitors like anastrozole or letrozole alongside CDK4/6 inhibitors. While key secondary endpoints such as PFS2 and overall survival (OS) remain immature at this stage, there is a noted trend towards improved PFS2 in the camizestrant group. The trial will continue as planned to further evaluate these critical secondary endpoints. Notably, SERENA-6 is the first global, double-blind Phase III trial utilizing circulating tumor DNA (ctDNA) to guide the detection of endocrine resistance. This innovative approach allows for early identification of endocrine resistance signs and the emergence of ESR1 mutations during routine tumor scans. Upon detection of ESR1 mutations without disease progression, patients transitioned from aromatase inhibitor therapy to camizestrant while maintaining treatment with the same CDK4/6 inhibitor. François-Clément Bidard, a professor of medical oncology at Université Versailles-Saint-Quentin, who is also the principal investigator of the trial, stated, “Patients urgently need new therapies to delay disease progression during first-line endocrine therapy. The SERENA-6 trial shows that transitioning to camizestrant after the emergence of ESR1 mutations can delay disease progression and extend the benefits of first-line treatment, representing a significant step forward for patients and a potential shift in clinical practice.” Susan Galbraith, Executive Vice President of Oncology Research and Development at AstraZeneca, noted that these impressive results indicate camizestrant’s versatility in combination with approved CDK4/6 inhibitors, offering a promising new treatment option for one-third of HR+ HER2-negative advanced breast cancer patients who develop ESR1 mutations while receiving aromatase inhibitors with CDK4/6 inhibitors. This pivotal outcome brings AstraZeneca closer to establishing camizestrant as a new standard of care, aiming to transform treatment paradigms in HR+ breast cancer. Globally, approximately 200,000 HR+ breast cancer patients receive first-line drug treatment, typically involving endocrine therapy targeting estrogen receptor-driven disease, often in conjunction with CDK4/6 inhibitors. However, many advanced patients develop resistance to these treatments. ESR1 mutations are key drivers of this resistance and are widely tested in clinical practice, becoming more prevalent as the disease progresses and associated with poor outcomes. About 30% of endocrine-sensitive HR+ patients experience ESR1 mutations during first-line treatment without disease progression.

Phase 3Clinical Result

26 Feb 2025

·www.businesswire.com

Camizestrant demonstrated highly statistically significant and clinically meaningful improvement in progression-free survival in 1st-line advanced HR-positive breast cancer with an emergent ESR1 tumor mutation in SERENA-6 Phase III trial

WILMINGTON, Del.--(BUSINESS WIRE)--Positive high-level results from a planned interim analysis of the SERENA-6 Phase III trial showed that AstraZeneca’s camizestrant in combination with a cyclin-dependent kinase (CDK) 4/6 inhibitor (palbociclib, ribociclib or abemaciclib) demonstrated a highly statistically significant and clinically meaningful improvement in the primary endpoint of progression-free survival (PFS). The trial evaluated switching to the camizestrant combination versus continuing standard-of-care treatment with an aromatase inhibitor (AI) (anastrozole or letrozole) in combination with a CDK4/6 inhibitor in the 1st-line treatment of patients with hormone receptor (HR)-positive, HER2-negative advanced breast cancer whose tumors have an emergent ESR1 mutation. The key secondary endpoints of time to second disease progression (PFS2) and overall survival (OS) were immature at the time of this interim analysis. However, the camizestrant combination demonstrated a trend toward improvement in PFS2. The trial will continue as planned to further assess key secondary endpoints. SERENA-6 is the first global, double-blind, registrational Phase III trial to use a circulating tumor DNA (ctDNA)-guided approach to detect the emergence of endocrine resistance and inform a switch in therapy before disease progression. The novel trial design used ctDNA monitoring at the time of routine tumor scan visits to identify patients for early signs of endocrine resistance and the emergence of ESR1 mutations. Following detection of an ESR1 mutation without disease progression, the endocrine therapy of patients was switched to camizestrant from ongoing treatment with an AI, while continuing combination with the same CDK4/6 inhibitor. François-Clément Bidard, MD, PhD, Professor of Medical Oncology at Institut Curie & UVSQ/Université Paris-Saclay, France, and co-principal investigator for the trial, said: “Patients have an urgent need for new treatments that delay disease progression on 1st-line endocrine-based therapies. The results from SERENA-6 show that switching from an aromatase inhibitor to camizestrant in combination with any of the three CDK4/6 inhibitors after emergence of an ESR1 mutation delays progression of disease and extends the benefit of 1st-line treatment, representing an important step forward for patients, and a potential shift in clinical practice.” Susan Galbraith, Executive Vice President, Oncology Hematology R&D, AstraZeneca, said: "These impressive results demonstrate the versatility of camizestrant in combination with all the widely approved CDK4/6 inhibitors to provide a well-tolerated new potential treatment option in the first-line setting for the one in three patients with HR-positive, HER2-negative advanced breast cancer whose tumors develop ESR1 mutations during treatment with an aromatase inhibitor in combination with a CDK4/6 inhibitor. This critical read-out moves us one step closer to realizing the potential of camizestrant to become a new standard-of-care as we look to shift the treatment paradigm and establish this new endocrine therapy backbone in HR-positive breast cancer.” The safety profile of camizestrant in combination with palbociclib, ribociclib or abemaciclib in SERENA-6 was consistent with the known safety profile of each medicine. No new safety concerns were identified and discontinuations were very low and similar in both arms. Globally, approximately 200,000 patients with HR-positive breast cancer are treated with a medicine in the 1st-line setting; most frequently with endocrine therapies that target estrogen receptor (ER)-driven disease, which are often paired with CDK4/6 inhibitors.1-3 However, resistance to CDK4/6 inhibitors and current endocrine therapies develops in many patients with advanced disease.3 Mutations in the ESR1 gene are a key driver of endocrine resistance and are widely tested for in clinical practice.4,5 These mutations develop during treatment of the disease, becoming more prevalent as the disease progresses and are associated with poor outcomes.4,5 Approximately 30% of patients with endocrine-sensitive HR-positive disease develop ESR1 mutations during 1st-line treatment without disease progression.1 Data will be presented at a forthcoming medical meeting and shared with global regulatory authorities. Notes HR-positive breast cancer Breast cancer is the second most common cancer and one of the leading causes of cancer-related deaths worldwide.6 More than two million patients were diagnosed with breast cancer in 2022, with more than 665,000 deaths globally.6 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.7 HR-positive breast cancer, characterized by the expression of estrogen or progesterone receptors, or both, is the most common subtype of breast cancer with 70% of tumors considered HR-positive and HER2-negative.7 ERs often drive the growth of HR-positive breast cancer cells.8 Once resistance to the treatment of HR-positive breast cancer with CDK4/6 inhibitors and current endocrine therapies occurs, treatment options are limited and survival rates are low with 35% of patients anticipated to live beyond five years after diagnosis.3,7,9 The optimization of endocrine therapy and overcoming resistance to enable patients to continue benefiting from these treatments, as well as identifying new therapies for those who are less likely to benefit, are active areas of focus for breast cancer research. SERENA-6 SERENA-6 is a Phase III, double-blind, randomized trial evaluating the efficacy and safety of camizestrant in combination with a CDK4/6 inhibitor (palbociclib, ribociclib or abemaciclib) versus treatment with an AI (anastrozole or letrozole) in combination with a CDK4/6 inhibitor (palbociclib, ribociclib or abemaciclib) in patients with HR-positive, HER2-negative advanced breast cancer (patients with either locally advanced disease, or metastatic disease) whose tumors have an emergent ESR1 mutation. The global trial enrolled 315 adult patients with histologically confirmed HR-positive, HER2-negative advanced breast cancer, undergoing treatment with an AI in combination with a CDK4/6 inhibitor as 1st-line treatment. The primary endpoint of the SERENA-6 trial is PFS as assessed by investigator, with secondary endpoints including OS, and PFS2 by investigator assessment. Camizestrant Camizestrant is an investigational, potent, next-generation oral selective estrogen receptor degrader (SERD) and complete ER antagonist that is currently in Phase III trials for the treatment of HR-positive breast cancer. AstraZeneca’s broad, robust and innovative clinical development program, including the SERENA-6, SERENA-4, CAMBRIA-1 and CAMBRIA-2 trials, is evaluating the safety and efficacy of camizestrant when used as a monotherapy or in combination with other agents to address a number of areas of unmet need in this specific type of breast cancer. Camizestrant has demonstrated anti-cancer activity across a range of preclinical models, including those with ER-activating mutations. In the SERENA-2 Phase II trial, camizestrant demonstrated PFS benefit versus fulvestrant irrespective of ESR1 mutation status or prior treatment with CDK4/6 inhibitors in patients with ER-positive locally advanced or metastatic breast cancer, previously treated with endocrine therapy. The SERENA-1 Phase I trial demonstrated that camizestrant is well tolerated and has a promising anti-tumor profile when administered alone or in combination with palbociclib, ribociclib and abemaciclib; three widely used CDK4/6 inhibitors. Combinations with other agents are ongoing in SERENA-1. 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 tumor environment. With fam-trastuzumab deruxtecan-nxki, a HER2-directed 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 fulvestrant and goserelin and aims to reshape the HR-positive space with first-in-class AKT inhibitor, capivasertib, the TROP-2-directed ADC, datopotamab deruxtecan-dlnk and next-generation oral SERD and potential new medicine camizestrant. PARP inhibitor olaparib is a targeted treatment option that has been studied in early and metastatic breast cancer patients with an inherited BRCA mutation. AstraZeneca with Merck & Co., Inc. (MSD outside the US and Canada) continue to research olaparib in these settings and to explore its potential in earlier disease. AstraZeneca is also exploring the efficacy and safety of saruparib, a potent and selective inhibitor of PARP1, in combination with camizestrant 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 datopotamab deruxtecan-dlnk alone and in combination with immunotherapy 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 catalyze 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 is a global, science-led biopharmaceutical company that focuses on the discovery, development, and commercialization of prescription medicines in Oncology, Rare Diseases, 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-us.com and follow the Company on social media @AstraZeneca. References Cerner CancerMPact database. Accessed February 2025. Lin M, et al. Comparative Overall Survival of CDK4/6 Inhibitors Plus Endocrine Therapy vs. Endocrine Therapy Alone for Hormone receptor-positive, HER2-negative metastatic breast cancer. J Cancer . 2020; 10.7150/jca.48944. Lloyd M R, et al. Mechanisms of Resistance to CDK4/6 Blockade in Advanced Hormone Receptor–positive, HER2-negative Breast Cancer and Emerging Therapeutic Opportunities. Clin Cancer Res . 2022; 28(5):821-30. Brett O, et al. ESR1 mutation as an emerging clinical biomarker in metastatic hormone receptor‑positive breast cancer. Breast Cancer Res . 2021; 23:85. Zundelevich, A, et al. ESR1 mutations are frequent in newly diagnosed metastatic and loco-regional recurrence of endocrine-treated breast cancer and carry worse prognosis. Breast Cancer Res. 2020 ; 22:16. Bray F, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin . 2024 Apr 4. doi: 10.3322/caac.21834. National Cancer Institute. Cancer Stat facts: Female breast cancer subtypes. Available at: https://seer.cancer.gov/statfacts/html/breast-subtypes.html . Accessed February 2025. 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. National Comprehensive Cancer Network. Clinical Practice Guidelines in Oncology (NCCN Guidelines). Available at: https://www.nccn.org/professionals/physician_gls/pdf/breast.pdf . Accessed February 2025. US-98587 | Last Updated 2/25

Clinical ResultPhase 3Phase 2Phase 1

100 Deals associated with Letrozole

External Link

KEGG	Wiki	ATC	Drug Bank
D00964	Letrozole	L02BG04	DB01006

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Infertility	Japan	Novartis Pharma AG	25 Feb 2022
Metastatic breast cancer	United States	Novartis Pharmaceuticals Corp.	25 Jul 1997
Breast Cancer	Sweden	Novartis AG	10 Dec 1996

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Endometrioid carcinoma ovary	Phase 3	Austria	Hoffmann-La Roche, Inc.	05 Nov 2020
Endometrioid carcinoma ovary	Phase 3	Austria	Novartis Pharmaceuticals Corp.	05 Nov 2020
Endometrioid carcinoma ovary	Phase 3	Germany	Novartis Pharmaceuticals Corp.	05 Nov 2020
Endometrioid carcinoma ovary	Phase 3	Germany	Hoffmann-La Roche, Inc.	05 Nov 2020
Endometrioid carcinoma ovary	Phase 3	Switzerland	Novartis Pharmaceuticals Corp.	05 Nov 2020
Endometrioid carcinoma ovary	Phase 3	Switzerland	Hoffmann-La Roche, Inc.	05 Nov 2020
Fallopian Tube Carcinoma	Phase 3	Austria	Novartis Pharmaceuticals Corp.	05 Nov 2020
Fallopian Tube Carcinoma	Phase 3	Austria	Hoffmann-La Roche, Inc.	05 Nov 2020
Fallopian Tube Carcinoma	Phase 3	Germany	Hoffmann-La Roche, Inc.	05 Nov 2020
Fallopian Tube Carcinoma	Phase 3	Germany	Novartis Pharmaceuticals Corp.	05 Nov 2020

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


Phase 2 study of letrozole, abemaciclib and metformin (AACR2025)	Phase 2	Recurrent Endometrial Cancer ER positive \| RB1 \| CCNE1 ... View more	25	Letrozole/Abemaciclib/Metformin	rpebxvbvep(nmstasmnln) = hesgsnlvwx jksktdtiah (svjmmwppft, 14.9% - 53.5) View more	Positive	29 Apr 2025
NCT05206448 (CLC II, CTgov)	Phase 4	Polycystic Ovary Syndrome \| Infertility \| Anovulation	190	letrozole (Letrozole)	qssyjuvokm = brdzsrbnlt bxvsfrisym (iydaplmcyu, iajagruekt - anphfzbgcc) View more	-	15 Apr 2025
				letrozole+Clomiphene Citrate (Letrozole + Clomiphene Citrate)	qssyjuvokm = yrcshrllzh bxvsfrisym (iydaplmcyu, zhuzsbboso - vnvzppsxka) View more
NCT03774472 (CTgov)	Phase 1/2	ER-positive/HER2-negative Breast Cancer \| Metastatic breast cancer	15	HCQ (HCQ at 400 mg)	fsotfmskry = ejzoksvesh lbbhdzplbs (dlwpspahyx, alybdnqozr - eziscdjwlm) View more	-	17 Feb 2025
				HCQ (HCQ at 600 mg)	fsotfmskry = zatfnsogao lbbhdzplbs (dlwpspahyx, putefdbmws - ifqgjqkjfg) View more
NCT05512780 (DARLING 01, Pubmed \| Breast Cancer Res) Manual	Phase 2	Hormone receptor positive HER2 negative breast cancer Neoadjuvant HER2 Negative \| Hormone Receptor Positive	29	Dalpiciclib + Letrozole	kxxkclbday(cflcxdkafc) = ipinbmtlov iuhqwzghzt (rvngcnkqrj ) View more	Positive	13 Feb 2025
NCT04294225 (CTgov)	Phase 2	Invasive Mammary Carcinoma \| Early Stage Breast Carcinoma	161	Letrozole+anastrozole	scvbwaumjn = cdfhzwctqg zqafcsxlpp (oauknrihzx, mmrvwfifyg - hptkxuyrey) View more	-	28 Jan 2025
NCT00382070 (NRG Oncology/NSABP B-42, Pubmed \| J Clin Oncol)	Phase 3	Hormone receptor positive breast cancer MammaPrint (MP)	-	Letrozole (MammaPrint high risk (MP-HR))	epfmxzhply(tmimrhdelq) = umvlgqrqjx iwoslbksdy (tpsexotcng, 0.34 - 1.24)	Positive	20 Oct 2024
				Letrozole (MammaPrint low risk (MP-LR))	epfmxzhply(tmimrhdelq) = coswkykwvr iwoslbksdy (tpsexotcng, 0.25 - 0.74) View more
NCT01127295 (PHACS, Pubmed)	Phase 4	Hormone receptor positive breast cancer Adjuvant CYP2A6 genotype	617	letrozole (CYP2A6 genotype)	rieurtxlmm(rqaehhevod) = Early relapse (19 patients) was not associated with model-estimated, concentration-based or declared adherence in the total population (p = 0.41, p = 0.37 and p = 0.45, respectively) cxvshufbww (mvutiubaus )	Positive	01 Aug 2024
NCT05918718 (Pubmed)	Phase 1/2	Pregnancy, Ectopic serum beta-human chorionic gonadotropin	88	Methotrexate	bjmcagbxjm(kzllpztqur) = urojqqlrog sozzkurwhs (thmfcxalmh )	Positive	17 Jun 2024
				5-day Letrozole	bjmcagbxjm(kzllpztqur) = mpjcupeebr sozzkurwhs (thmfcxalmh ) View more
NCT04049227 (ASCO2024) Manual	Early Phase 1	Endometrial Endometrioid Adenocarcinoma	25	Abemaciclib 1Letrozole	socdawodfe(qhfaqshxfl) = wqfwkqpsat yhdjjxknfj (dozsdgzzsq, 23) View more	Positive	24 May 2024
				Abemaciclib.5Letrozole	socdawodfe(qhfaqshxfl) = smuvnxtwxb yhdjjxknfj (dozsdgzzsq )
ASCO2024	Phase 2	Endometrial Carcinoma CTNNB1 \| KRAS \| CDKN2Amutation ... View more	28	Letrozole/abemaciclib	qbxkecdbdu(wrqunsmfnc) = mzlgoogyat zekntfpahd (yuadsxmdcw ) View more	Positive	24 May 2024

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