Background:
Premature ovarian insufficiency (POI) is a condition in which women under the age of 40 years have absent or irregular menstrual cycles. POI can cause infertility, signs of menopause, osteoporosis, and other symptoms. Hormone replacement therapy (HRT) is a treatment that gives women extra hormones, such as estrogen and progesterone. HRT works well in adult women. Researchers want to find the most effective doses and regimens for adolescents.
Objective:
To monitor the effects of HRT on adolescents with POI.
Eligibility:
Female adolescents aged 11 to 19 years diagnosed with POI. Healthy volunteers are also needed.
Design:
All participants will have clinic visits every 6 months for 2 years. Each visit may last 2 days. Each visit may include:
Blood and urine tests.
A test of their heart function.
A test to measure the stiffness of their blood vessels. Participants will lie flat with a blood pressure cuff on a leg and a meter on the neck while the cuff inflates.
A test of their grip strength. Participants will squeeze a handheld device as hard as they can.
Two scans to measure bone density. For one, participants will lie on a table while a scanner passes along their body. For the other, participants will sit in a chair and insert their forearm, then their lower leg, into a scanner.
A test to measure skin pigmentation. Participants skin will be touched lightly with a device.
An optional visual exam of the vagina. Some vaginal fluid may also be collected with a cotton swab/cytobrush.
Participants with POI will receive HRT. They will be given estrogen patches and progesterone pills.

Start Date09 Jun 2025

Sponsor / Collaborator-

CTRI/2024/05/068054

/ Not yet recruitingNot ApplicableIIT

To study the utility of Estrogen Receptor and Progesterone Receptor expression as an immunohistochemical predictive markers for tumour behaviour in comparison to histopathological parameters and Tumour, Lymph Node and Metastatic staging in colorectal carcinoma - Nil

Start Date10 Jun 2024

Sponsor / Collaborator-

IRCT20240207060932N1

/ SuspendedPhase 3IIT

Comparison of the effects of Persicaria hydropiper vaginal cream based on coconut oil and sesame oil with conjugated estrogen vaginal cream and placebo on vaginal atrophy and sexual function of postmenopausal women.

Start Date08 Apr 2024

Sponsor / Collaborator-

100 Clinical Results associated with Estrogens, Conjugated

100 Translational Medicine associated with Estrogens, Conjugated

100 Patents (Medical) associated with Estrogens, Conjugated

9,362

Literatures (Medical) associated with Estrogens, Conjugated

31 Dec 2025·JOURNAL OF OBSTETRICS AND GYNAECOLOGY

Simvastatin-loaded liposomal nanoparticles as treatment for adenomyosis in a patient-derived xenograft mouse model: a pilot study

Article

Author: Kilic, Gokhan S. ; Saada, Jamal ; Ozpolat, Bulent ; Yang, Jinping ; Borahay, Mostafa A. ; Vincent, Kathleen L. ; Kirschen, Gregory W. ; Motamedi, Massoud ; Michel, Rachel

BACKGROUND:

Adenomyosis is a common gynaecological condition where ectopic endometrial glands and stroma grow within the myometrium. This condition has a high clinical burden impacting those afflicted with debilitating symptoms including heavy painful periods. Simvastatin is an oral hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor, typically used to treat hyperlipidaemia. Simvastatin has recently shown promise for treating gynaecological conditions such as endometriosis and uterine fibroids with nanoliposomal formulations demonstrating improved efficacy. In this pilot study, we tested simvastatin-loaded liposomal nanoparticles on xenografted adenomyosis tissues in a patient-derived mouse model.

METHODS:

We surgically inserted oestrogen/progesterone pellets into mice, followed by adenomyosis tissue xenografts 15 days later. Mice were then randomised into three groups: control, simvastatin, and simvastatin-loaded liposomal nanoparticles (simvastatin-NP). We quantified the changes in adenomyosis xenograft size weekly using a calliper as well as ultrasound imaging 28 days after treatment, prior to sacrifice. We also measured the proliferation of biomarker Ki67 in the xenografted tissues using immunohistochemistry after animal sacrifice.

RESULTS:

Treatment with simvastatin-NP significantly reduced volume and weight of adenomyosis xenografts while attenuating Ki67 expression when compared to the control and simvastatin groups. Conclusions: This pilot study demonstrates promising improved efficacy of simvastatin delivered via liposomal nanoparticles. However, larger studies are needed to fully explore the potential of simvastatin-NP in adenomyosis.

01 Jul 2025·MATURITAS

Cardiovascular disease and female sexual health across the life span: a bidirectional link

Review

Author: Armeni, Eleni ; Armeni, Anastasia ; Chedraui, Peter ; Lambrinoudaki, Irene

Epidemiological research reveals that around 40 % of women aged 18-59 report significant concerns about their sexual experiences. Endothelial function and proper arterial blood flow through the hypogastric and pudendal arteries are critical in women for a normal vasculogenic response to sexual stimulation. Organic causes of female sexual dysfunction (FSD) often stem from neuropathy or vascular complications linked to cardiovascular risk factors. The relationship between cardiovascular disease (CVD) and FSD is multifactorial, influenced by various factors such as disease severity, physical and physiological factors, social determinants and factors related to medication use. Additionally, the pathophysiological mechanisms implicated in FSD of CVD patients include vascular, physical, psychological and hormonal factors. Hypertension, stroke, and myocardial infarction are closely interrelated with FSD, which is not the case for coronary heart disease, dyslipidemia, and peripheral obstructive artery disease. Hormonal treatment for sexual dysfunction in women with cardiovascular risk factors is discussed, concerning menopausal hormone therapy, tibolone, selective estrogen receptor modulators, vaginal estrogen, prasterone and testosterone therapy. On the other hand, the beneficial effect of sexual activity on cardiovascular health has been gaining supportive evidence. In healthy postmenopausal women aged 45-60, penile-vaginal intercourse has been suggested to positively influence cardiac autonomic functions, as indicated by heart rate variability. However, effectively addressing the challenges of aging and further highlighting the positive impact of sexual activity on cardiac health in selected female populations could significantly enhance life motivation and promote a healthy lifestyle during this stage. The present review elucidates the bidirectional relationship between CVD and female sexual function.

01 Jul 2025·JOURNAL OF CLINICAL NEUROSCIENCE

Disproportionality analysis of progestogens and estrogens demonstrates increased meningioma risk

Article

Author: Frey, Connor ; Etminan, Mahyar

OBJECTIVE:

This study aims to clarify the relationship between the use of various progestogens and estrogens and the risk of developing meningiomas, given the widespread prescription of hormonal contraceptives and their potential implications in tumour proliferation.

METHODS:

Data from the FDA Adverse Event Reporting System (FAERS) was analyzed using disproportionality analysis to assess the association between specific progestogens and estrogens and meningioma risk. Reporting odds ratios (RORs) and 95% confidence intervals (CIs) were calculated to quantify these associations.

RESULTS:

Among progestogens, promegestone showed the highest risk with an ROR of 2620.651 (95% CI: 982.032, 6993.474), followed by medrogestone with an ROR of 871.475 (95% CI: 256.382, 2962.253) and dydrogesterone with moderate risk (ROR 113.802; 95% CI: 60.676, 213.444). For estrogens, estradiol exhibited the highest risk (ROR 17.786; 95% CI: 14.875, 21.266), followed by ethinyl estradiol (ROR 7.441; 95% CI: 6.099, 9.080), while conjugated estrogens showed a lower risk (ROR 1.736; 95% CI: 1.043, 2.889). No cases were reported for estriol, estrone, or mestranol, indicating a potentially lower risk profile for these estrogens.

CONCLUSION:

The study reveals significant variations in meningioma risk associated with different hormonal therapies. Certain progestogens and estrogens present notably higher risks, emphasizing the need for personalized risk assessments in hormonal therapy prescriptions. These findings advocate for further research to better understand meningioma risk linked to hormone-based contraceptives, supporting safer clinical decision-making.

News (Medical) associated with Estrogens, Conjugated

01 Jun 2025

·www.icr.ac.uk

Next-generation breast cancer drug targets tumours before they have a chance to grow

A powerful new drug for advanced breast cancer can be used to treat emerging tumours, months before they have a chance to grow, helping to keep patients well for longer and delaying the need for later-line therapies including chemotherapy. Results of a global study, funded by AstraZeneca and co-led by researchers at The Institute of Cancer Research, London, The Royal Marsden NHS Foundation Trust and Institut Curie, Paris, were presented at the American Society of Clinical Oncology (ASCO) annual meeting in Chicago on 1 June 2025. The results found that patients with advanced hormone receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER2-) breast cancer who were given the new drug, called camizestrant, in combination with a CDK4/6 inhibitor cut the chances of their cancer getting worse by over half (56 per cent), allowing them to stay on first-line therapy for longer. The SERENA-6 phase III trial is also the first global trial to demonstrate that using circulating tumour DNA (ctDNA) blood tests to guide treatment at the right time — before clinical signs of progression appear — has a significant clinical benefit for this group of patients. Findings from the trial were simultaneously published in The New England Journal of Medicine. Experts now hope the findings have the potential to become a new treatment strategy for patients with this common type of advanced breast cancer. Around 55,000 women are diagnosed with breast cancer in the UK every year and 11,500 will die from the disease. Around 70 per cent of patients have HR+, HER2- breast cancer. Some patients go on to develop mutations in a gene called ESR1 gene, which programmes the oestrogen receptor, allowing the cancer to grow and resist hormone-blocking treatments. Although ESR1 mutations are rare at diagnosis of advanced breast cancer, they emerge during first-line therapy in around 40 per cent of patients. First-line therapy for HR+, HER2‑ advanced breast cancer is usually a cyclin-dependent kinase (CDK) 4 and 6 inhibitor drug plus an aromatase inhibitor (a type of hormone treatment). If this treatment fails, chemotherapy can be an option but delaying this is highly important for patients because of the toxic side effects it brings. Camizestrant, which was discovered and developed by AstraZeneca, is a type of drug described as a ‘next-generation’ oral selective estrogen receptor degrader (SERD). It works by blocking and breaking down oestrogen receptors in breast cancer cells. Camizestrant was designed to target the ESR1 mutations tested for in the ctDNA blood tests. Camizestrant not only prevents oestrogen from attaching to cancer cells but also destroys the receptors themselves, making it harder for the cancer to resist treatment. The SERENA-6 study tested whether switching to camizestrant from an aromatase inhibitor, whilst continuing treatment with the same CDK 4/6 inhibitor to treat tumours with emerging ESR1 mutations could extend the benefit of first line treatment and delay the need for later-line therapies. To be eligible to take part in the study, 3,325 patients with HR+, HER2 negative advanced breast cancer (who had been on first-line treatment for at least six months) from 23 countries were screened for ESR1 mutations using ctDNA testing every 8-12 weeks. Of that number, 548 patients tested positive for ESR1 mutations during the screening period, and 315 were randomised onto the study. Half of the patients were given camizestrant, alongside their CDK4/6 inhibitor plus a dummy pill instead of their aromatase inhibitor. Patients on the control arm continued with their aromatase inhibitor and CDK4/6 inhibitor plus a dummy pill instead of camizestrant. The results showed that the camizestrant combination reduced the risk of breast cancer progression or death by over half (56 per cent), based on the reported hazard ratio of 0.44. The median progression free survival time for patients taking the camizestrant combination was 16 months, compared with 9.2 months for patients on the control arm. The camizestrant combination was well tolerated, with only a few patients (1 per cent) experiencing side effects that led them to discontinue the treatment. The results also showed that the therapy regime reduced the risk of a deterioration in patients’ general health and quality of life by 47 per cent (based on the reported hazard ratio of 0.53), compared with the control group, demonstrating the benefit of patients remaining on first-line therapy. The Breast Cancer Clinical Trials Team that co-led the SERENA-6 trial are based in the Ralph Lauren Research Wing, Kuok Research Centre within the Oak Cancer Centre, which was funded by The Royal Marsden Cancer Charity. Scientists working in the Breast Cancer Now Toby Robins Research Centre at the ICR and The Ralph Lauren Centre for Breast Cancer Research at The Royal Marsden, funded by The Royal Marsden Cancer Charity, and The National Institute for Health and Care Research Royal Marsden Biomedical Research Centre, have been leading pioneering research into the use of liquid biopsies to detect breast cancer relapse and guide treatment for more than a decade. Co-principal investigator Professor Nick Turner, Professor of Molecular Oncology at The Institute of Cancer Research, London, and Director of Clinical Research and Consultant Medical Oncologist at The Royal Marsden NHS Foundation Trust, said: “This is a pivotal moment in breast cancer care. These results demonstrate that using liquid biopsy blood tests to spot emerging resistance in tumours, before they start to grow and make the patient unwell, can guide early intervention with camizestrant to delay disease progression in patients with ESR1 mutations. “This proactive approach not only extends the benefit of first line therapy but also redefines how we think about drug resistance in this type of breast cancer. This is a potential new treatment strategy in oncology to treat developing resistance before it causes disease progression. “Ongoing trials are also examining the use of camizestrant in broader first-line populations from the start of their treatment, as well as in the early breast cancer setting, to determine how best to integrate camizestrant into long-term treatment strategies to benefit breast cancer patients.” Professor Kristian Helin, Chief Executive of The Institute of Cancer Research, London, said: “The results of the SERENA-6 trial represent more than a clinical milestone – they represent a transformational shift in how we approach precision medicine. "The Institute of Cancer Research has played a major role in advancing ctDNA testing for breast cancer, particularly in early detection and relapse prediction – so it is very exciting to see this technology being used to delay disease progression in patients and extend the benefits of first-line treatment in patients with this type of advanced breast cancer and delay the need for chemotherapy for as long as possible. “These breakthroughs are helping shape personalised breast cancer treatment, allowing doctors to adjust therapies earlier and improve patient outcomes.” Professor Nicholas van As, Chief Medical Officer at The Royal Marsden NHS Foundation Trust, said: “Innovative ctDNA trials at The Royal Marsden have transformed the way clinicians tailor cancer treatments and detect relapse in patients before clinical signs of progression appear. “It is hugely exciting that the SERENA-6 trial has evolved this thinking and clinicians can use it to personalise kinder treatments regimes for this group of patients and improve their outcome.”

Clinical ResultPhase 3ASCO

31 May 2025

·www.globenewswire.com

New data show Roche’s Itovebi significantly extended survival in a certain type of HR-positive advanced breast cancer

The ItovebiTM (inavolisib)-based regimen reduced the risk of death by more than 30% in people with PIK3CA-mutated HR-positive, HER2-negative advanced breast cancer, compared with palbociclib and fulvestrant alone1The PIK3CA mutation is found in approximately 40% of HR-positive advanced breast cancers and is associated with a poor prognosis2,3New data are being presented in an oral session at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting and published in the New England Journal of Medicine1 Basel, 31 May 2025 - Roche (SIX: RO, ROG; OTCQX: RHHBY) announced today positive final results from the overall survival (OS) analysis of the phase III INAVO120 study. These data showed ItovebiTM (inavolisib), in combination with palbociclib (Ibrance®) and fulvestrant, reduced the risk of death by more than 30% compared with palbociclib and fulvestrant alone. This represents a statistically significant and clinically meaningful improvement in overall survival for people with PIK3CA-mutated, hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, endocrine-resistant, locally advanced or metastatic breast cancer.1 The results are being presented in an oral session at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting and simultaneously published in the New England Journal of Medicine (NEJM).1 "For the first time, a PI3K pathway-targeted drug has shown it can help people with this breast cancer subtype live longer," said Levi Garraway, M.D., Ph.D., Roche’s Chief Medical Officer and Head of Global Product Development. "Itovebi exemplifies our continued commitment to improve survival rates for people with this common PIK3CA mutation, for whom more effective treatment options are needed.” “The landmark data for the inavolisib-based regimen showed not only a doubling in progression-free survival, but importantly that it extended lives and gave people more time without chemotherapy,” said Professor Nicholas Turner, Lead Study Author and Professor of Molecular Oncology at The Institute of Cancer Research, and Consultant Medical Oncologist at The Royal Marsden NHS Foundation Trust, London, United Kingdom. “These results give us confidence that this regimen could become the new standard of care in the first-line setting, having demonstrated a substantial benefit on patient outcomes and quality of life.” The Itovebi-based regimen demonstrated a meaningful OS benefit compared with palbociclib and fulvestrant alone.1 The median OS was 34.0 months (95% CI: 28.4–44.8) for people in the Itovebi arm, compared with 27.0 months (95% CI: 22.8–38.7) in the palbociclib and fulvestrant arm (stratified hazard ratio [HR]=0.67; 95% CI: 0.48–0.94, p-value=0.0190 [boundary=0.0469]).1 The benefit seen in delaying cancer progression was maintained in the updated analysis, with the Itovebi-based regimen showing a consistent improvement in median progression free survival of 17.2 months versus 7.3 months (stratified HR=0.42; 95% CI: 0.32-0.55) in the comparator arm.1 The Itovebi-based regimen also led to a statistically significant improvement in objective response rate (the percentage of patients whose signs of cancer completely disappear or their tumours shrink significantly after treatment) and ad-hoc exploratory analyses showed it substantially delayed time to chemotherapy by approximately two years (stratified HR=0.43; 95% CI: 0.30-0.60).1 No new safety signals were observed at the time of the final OS analysis, with a low discontinuation due to adverse events supporting good tolerability.1 The Itovebi-based regimen is approved in the United States, Switzerland, Canada, Australia, United Arab Emirates and China. In May, it received a positive opinion from the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP), with a final decision regarding the approval expected from the European Commission in the near future. Data from the INAVO120 study are currently under review with other global health authorities. Beyond INAVO120, Itovebi is currently being investigated in three company-sponsored phase III studies (INAVO121, INAVO122, INAVO123), all in PIK3CA-mutated, locally advanced or metastatic breast cancer in various combinations.4-7 We are exploring additional studies in breast cancer and other tumour types with the hope of providing the benefit of this targeted therapy to more people with PIK3CA mutations. About Itovebi TM (inavolisib)Itovebi is an oral, targeted treatment that has been shown to provide well-tolerated and durable disease control in people with PIK3CA-mutated, hormone receptor-positive, human epidermal growth factor receptor 2-negative, advanced breast cancer, who often have a poor prognosis and are in urgent need of new treatment options.2,3,8 Itovebi has been designed to help minimise the overall burden and toxicity of treatment and is differentiated from other PI3K inhibitors due to its high potency and specificity for the PI3K alpha isoform versus other isoforms, and unique mechanism of action that facilitates the degradation of mutated PI3K alpha.9,10 About the INAVO120 studyThe INAVO120 study [NCT04191499] is a phase III, randomised, double-blind, placebo-controlled study evaluating the efficacy and safety of Itovebi™ (inavolisib) in combination with palbociclib and fulvestrant versus placebo plus palbociclib and fulvestrant in people with PIK3CA-mutated, hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, locally advanced or metastatic breast cancer whose disease progressed during treatment or within 12 months of completing adjuvant endocrine therapy and who have not received prior systemic therapy for metastatic disease.4 The study included 325 patients, who were randomly assigned to either the investigational or control treatment arm.4 The primary endpoint is progression-free survival, as assessed by investigators, defined as the time from randomisation in the clinical trial to the time when the disease progresses, or a patient dies from any cause.4 Secondary endpoints include overall survival, objective response rate, and clinical benefit rate.4 Beyond INAVO120, Itovebi is currently being investigated in three additional company-sponsored phase III clinical studies in PIK3CA-mutated locally advanced or metastatic breast cancer in various combinations:5-7 in combination with fulvestrant versus alpelisib plus fulvestrant in HR-positive/HER2-negative breast cancer post cyclin-dependent kinase 4/6 (CDK4/6) inhibitor and endocrine combination therapy (INAVO121; NCT05646862).in combination with pertuzumab plus trastuzumab for subcutaneous injection (SC) versus pertuzumab plus trastuzumab for SC and optional physician's choice of endocrine therapy as a maintenance treatment in HER2-positive disease (INAVO122; NCT05894239).in combination with CDK4/6 inhibitor and letrozole versus placebo plus a CDK4/6 inhibitor and letrozole in the first-line setting in PIK3CA-mutated HR-positive/HER2-negative, endocrine-sensitive breast cancer (INAVO123; NCT06790693). About hormone receptor (HR)-positive breast cancerHR-positive breast cancer is the most prevalent type of all breast cancers, accounting for approximately 70% of cases.11,12 A defining feature of HR-positive breast cancer is that its tumour cells have receptors that attach to one or both hormones – oestrogen or progesterone – which can contribute to tumour growth. People diagnosed with HR-positive metastatic breast cancer often face the risk of disease progression and treatment side effects, creating a need for additional treatment options.12-14 The PI3K signalling pathway is commonly dysregulated in HR-positive breast cancer, often due to activating PIK3CA mutations, which have been identified as a potential mechanism of intrinsic resistance to standard of care endocrine therapy in combination with cyclin-dependent kinase 4/6 inhibitors.3 About Roche in breast cancerRoche has been advancing breast cancer research for more than 30 years with the goal of helping as many people with the disease as possible. Our medicines, along with companion diagnostic tests, have contributed to bringing breakthrough outcomes in human epidermal growth factor 2-positive and triple-negative breast cancers. As our understanding of breast cancer biology rapidly improves, we are working to identify new biomarkers and approaches to treatment for other subtypes of the disease, including oestrogen receptor-positive breast cancer, which is a form of hormone receptor-positive breast cancer, the most prevalent type of all breast cancers.11,12About Roche Founded in 1896 in Basel, Switzerland, as one of the first industrial manufacturers of branded medicines, Roche has grown into the world’s largest biotechnology company and the global leader in in-vitro diagnostics. The company pursues scientific excellence to discover and develop medicines and diagnostics for improving and saving the lives of people around the world. We are a pioneer in personalised healthcare and want to further transform how healthcare is delivered to have an even greater impact. To provide the best care for each person we partner with many stakeholders and combine our strengths in Diagnostics and Pharma with data insights from the clinical practice. For over 125 years, sustainability has been an integral part of Roche’s business. As a science-driven company, our greatest contribution to society is developing innovative medicines and diagnostics that help people live healthier lives. Roche is committed to the Science Based Targets initiative and the Sustainable Markets Initiative to achieve net zero by 2045. Genentech, in the United States, is a wholly owned member of the Roche Group. Roche is the majority shareholder in Chugai Pharmaceutical, Japan. For more information, please visit www.roche.com. All trademarks used or mentioned in this release are protected by law.References[1] Turner NC, et al. INAVO120 Phase III trial final overall survival (OS) analysis of first-line inavolisib (INAVO)/placebo (PBO) + palbociclib (PALBO) + fulvestrant (FULV) in patients (pts) with PIK3CA-mutated, hormone receptor-positive (HR+), HER2-negative (HER2–), endocrine-resistant advanced breast cancer (aBC). Presented at the American Society of Clinical Oncology (ASCO) Annual Meeting, 2025 May 30-June 03; Chicago, USA. Abstract #1003.[2] Fillbrunn M, et al. PIK3CA mutation status, progression and survival in advanced HR+/HER2- breast cancer: a meta-analysis of published clinical trials. BMC Cancer. 2022;22(1):1002.[3] Anderson E, et al. A Systematic Review of the Prevalence and Diagnostic Workup of PIK3CA Mutations in HR+/HER2– Metastatic Breast Cancer. Int J Breast Cancer. 2020;2020:3759179.[4] ClinicalTrials.gov. A Study Evaluating the Efficacy and Safety of Inavolisib + Palbociclib + Fulvestrant vs Placebo + Palbociclib + Fulvestrant in Patients With PIK3CA-Mutant, Hormone Receptor-Positive, Her2-Negative, Locally Advanced or Metastatic Breast Cancer (INAVO120) [Internet; cited 2025 May]. Available from: https://classic.clinicaltrials.gov/ct2/show/NCT04191499. [5] ClinicalTrials.gov. A Study Evaluating the Efficacy and Safety of Inavolisib Plus Fulvestrant Compared With Alpelisib Plus Fulvestrant in Participants With HR-Positive, HER2-Negative, PIK3CA Mutated, Locally Advanced or Metastatic Breast Cancer Post CDK4/6i and Endocrine Combination Therapy (INAVO121) [Internet; cited 2025 May]. Available from: https://classic.clinicaltrials.gov/ct2/show/NCT05646862. [6] ClinicalTrials.gov. A Study to Evaluate the Efficacy and Safety of Inavolisib in Combination With Phesgo Versus Placebo in Combination With Phesgo in Participants With PIK3CA-Mutated HER2-Positive Locally Advanced or Metastatic Breast Cancer (INAVO122) [Internet; cited 2025 May]. Available from: https://classic.clinicaltrials.gov/ct2/show/NCT05894239. [7] ClinicalTrials.gov. A Study Evaluating the Efficacy and Safety of Inavolisib Plus CDK4/6 Inhibitor and Letrozole vs Placebo + CDK4/6i and Letrozole in Participants With Endocrine-Sensitive PIK3CA-Mutated, Hormone Receptor-Positive, HER2-Negative Advanced Breast Cancer (INAVO123) [Internet; cited 2025 May]. Available from: https://clinicaltrials.gov/study/NCT06790693.[8] Turner NC, et al. Inavolisib-Based Therapy in PIK3CA-Mutated Advanced Breast Cancer. NEJM. 2024;391(17):1584-96.[9] Juric D, et al. A phase I/Ib study of inavolisib (GDC-0077) in combination with fulvestrant in patients (pts) with PIK3CA-mutated hormone receptor-positive/HER2-negative (HR+/HER2–) metastatic breast cancer. Presented at San Antonio Breast Cancer Symposium, 2020 December 7-10; San Antonio, USA. Abstract #P5-17-05.[10] Hong R, et al. GDC-0077 is a selective PI3K alpha inhibitor that demonstrates robust efficacy in PIK3CA mutant breast cancer models as a single agent and in combination with standard of care therapies. Cancer Res. 2018;78(4):4-14.[11] National Cancer Institute: Surveillance, Epidemiology and Ends Result Program. Cancer Stat Facts: Female Breast Cancer Subtypes [Internet; cited 2025 May]. Available from: https://seer.cancer.gov/statfacts/html/breast-subtypes.html. [12] Lim E, et al. The natural history of hormone receptor-positive breast cancer. Oncology (Williston Park). 2012;26(8):688-94,696.[13] Tomas R and Barrios CH. Optimal management of hormone receptor positive metastatic breast cancer in 2016. Ther Adv Med Oncol. 2015;7(6):304-20.[14] Galipeau N, et al. Understanding key symptoms, side effects, and impacts of HR+/HER- advanced breast cancer: qualitative study findings. J Patient-Rep Outcomes. 2019;3(1):10. Roche Global Media RelationsPhone: +41 61 688 8888 / e-mail: media.relations@roche.com Hans Trees, PhDPhone: +41 79 407 72 58 Sileia UrechPhone: +41 79 935 81 48 Nathalie AltermattPhone: +41 79 771 05 25 Lorena CorfasPhone: +41 79 568 24 95 Simon GoldsboroughPhone: +44 797 32 72 915 Karsten KleinePhone: +41 79 461 86 83 Nina MählitzPhone: +41 79 327 54 74 Kirti PandeyPhone: +49 172 6367262 Yvette PetillonPhone: +41 79 961 92 50 Dr Rebekka SchnellPhone: +41 79 205 27 03 Roche Investor Relations Dr Bruno EschliPhone: +41 61 68-75284e-mail: bruno.eschli@roche.com Dr Sabine BorngräberPhone: +41 61 68-88027e-mail: sabine.borngraeber@roche.com Dr Birgit MasjostPhone: +41 61 68-84814e-mail: birgit.masjost@roche.com Investor Relations North America Loren KalmPhone: +1 650 225 3217e-mail: kalm.loren@gene.com Attachment 31052025_INAVO120 study Itovebi_en

Phase 3Clinical ResultASCODrug Approval

26 May 2025

·www.globenewswire.com

CHMP recommends EU approval of Roche’s Itovebi for PIK3CA-mutated, ER-positive, HER2-negative, advanced breast cancer

Positive recommendation based on phase III INAVO120 data showing ItovebiTM (inavolisib) in combination with palbociclib and fulvestrant more than doubled progression-free survival in the first-line setting1 The Itovebi-based regimen also demonstrated a statistically significant and clinically meaningful benefit in overall survival (OS) in the final OS analysis Final OS data will be presented in an oral session at the 2025 American Society of Clinical Oncology Annual Meeting 23 May 2025 - Roche (SIX: RO, ROG; OTCQX: RHHBY) announced today that the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has adopted a positive opinion for Itovebi™ (inavolisib), in combination with palbociclib (Ibrance®) and fulvestrant, for the treatment of adult patients with PIK3CA-mutated, oestrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative, locally advanced or metastatic breast cancer, following recurrence on or within 12 months of completing adjuvant endocrine treatment. If approved, the Itovebi-based regimen has the potential to transform the standard of care in this first-line setting, where treatments are currently limited.1 A final decision regarding the approval is expected from the European Commission in the near future. “The positive CHMP recommendation for the Itovebi-based regimen represents a significant step towards providing people in the EU with PIK3CA-mutated, ER-positive advanced breast cancer with a targeted therapy in the first-line setting,” said Levi Garraway, M.D., Ph.D., Roche’s Chief Medical Officer and Head of Global Product Development. “This recommendation is further enforced by the recent final overall survival results from the INAVO120 study, showing the regimen can meaningfully extend survival.” The presence of a PIK3CA mutation, found in approximately 40% of hormone receptor (HR)-positive breast cancers, can make the disease more aggressive and worsen survival outcomes.2,3 This underscores the importance of testing for PIK3CA mutations prior to first-line treatment so that people with a poor prognosis can benefit from an effective, PI3K-targeted therapy as soon as possible. The CHMP’s positive opinion is based on the phase III INAVO120 results, published in the New England Journal of Medicine in October 2024, which showed a 57% reduction in the risk of disease worsening or death (progression-free survival [PFS]) with the Itovebi-based regimen compared with palbociclib and fulvestrant alone (15.0 months vs. 7.3 months; hazard ratio [HR]=0.43, 95% CI: 0.32-0.59, p1 The PFS benefit was consistent across all pre-specified subgroups, including people whose disease had spread to three or more locations, characterised as difficult-to-treat disease.1 The Itovebi-based regimen was well tolerated, with no new safety signals observed.1 Positive topline results from the final overall survival (OS) analysis, announced in January 2025, showed a statistically significant and clinically meaningful OS benefit with the Itovebi-based regimen. OS data were immature at the time of primary analysis, but a clear positive trend was observed (stratified HR=0.64, 95% CI: 0.43-0.97, p=0.0338 (boundary of 0.0098)).1 The full results from the OS analysis will be presented in an oral session at the 2025 American Society of Clinical Oncology Annual Meeting. The Itovebi-based regimen is approved for the treatment of adults with endocrine-resistant, PIK3CA-mutated, HR-positive, HER2-negative, locally advanced or metastatic breast cancer in the United States, Switzerland, Canada, Australia, United Arab Emirates and China, with data from INAVO120 under review with other global health authorities. Beyond INAVO120, Itovebi is currently being investigated in three company-sponsored phase III studies (INAVO121, INAVO122, INAVO123), all in PIK3CA-mutated, locally advanced or metastatic breast cancer in various combinations.4-7 We are exploring additional studies in breast cancer and other tumour types with the hope of providing the benefit of this targeted therapy to more people with PIK3CA mutations. Itovebi is an oral, targeted treatment that has been shown to provide well-tolerated and durable disease control in people with advanced PIK3CA-mutated, hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer, who often have a poor prognosis and are in urgent need of new treatment options.1-3 Itovebi has been designed to help minimise the overall burden and toxicity of treatment and is differentiated from other PI3K inhibitors due to its high potency and specificity for the PI3K alpha isoform versus other isoforms, and unique mechanism of action that facilitates the degradation of mutated PI3K alpha.8,9 The INAVO120 study [NCT04191499] is a phase III, randomised, double-blind, placebo-controlled study evaluating the efficacy and safety of Itovebi™ (inavolisib) in combination with palbociclib and fulvestrant versus placebo plus palbociclib and fulvestrant in people with PIK3CA-mutated, hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, locally advanced or metastatic breast cancer whose disease progressed during treatment or within 12 months of completing adjuvant endocrine therapy and who have not received prior systemic therapy for metastatic disease.4 The study included 325 patients, who were randomly assigned to either the investigational or control treatment arm.4 The primary endpoint is progression-free survival, as assessed by investigators, defined as the time from randomisation in the clinical trial to the time when the disease progresses, or a patient dies from any cause.4 Secondary endpoints include overall survival, objective response rate, and clinical benefit rate.4 Beyond INAVO120, Itovebi is currently being investigated in three additional company-sponsored phase III clinical studies in PIK3CA-mutated, locally advanced or metastatic breast cancer in various combinations:5-7 in combination with fulvestrant versus alpelisib plus fulvestrant in HR-positive/HER2-negative breast cancer post cyclin-dependent kinase 4/6 (CDK4/6) inhibitor and endocrine combination therapy (INAVO121; NCT05646862). in combination with pertuzumab plus trastuzumab for subcutaneous injection (SC) versus pertuzumab plus trastuzumab for SC and optional physician's choice of endocrine therapy as a maintenance treatment in HER2-positive disease (INAVO122; NCT05894239). in combination with a CDK4/6 inhibitor and letrozole versus placebo plus a CDK4/6 inhibitor and letrozole in the first-line setting in PIK3CA-mutated HR-positive/HER2-negative, endocrine-sensitive breast cancer (INAVO123; NCT06790693). HR-positive breast cancer is the most prevalent type of all breast cancers, accounting for approximately 70% of cases.10,11 A defining feature of HR-positive breast cancer is that its tumour cells have receptors that attach to one or both hormones – oestrogen or progesterone – which can contribute to tumour growth. People diagnosed with HR-positive metastatic breast cancer often face the risk of disease progression and treatment side effects, creating a need for additional treatment options.11-13 The PI3K signalling pathway is commonly dysregulated in HR-positive breast cancer, often due to activating PIK3CA mutations, which have been identified as a potential mechanism of intrinsic resistance to standard of care endocrine therapy in combination with cyclin-dependent kinase 4/6 inhibitors.3 Roche has been advancing breast cancer research for more than 30 years with the goal of helping as many people with the disease as possible. Our medicines, along with companion diagnostic tests, have contributed to bringing breakthrough outcomes in human epidermal growth factor 2-positive and triple-negative breast cancers. As our understanding of breast cancer biology rapidly improves, we are working to identify new biomarkers and approaches to treatment for other subtypes of the disease, including oestrogen receptor-positive breast cancer, which is a form of hormone receptor-positive breast cancer, the most prevalent type of all breast cancers.10,11 Founded in 1896 in Basel, Switzerland, as one of the first industrial manufacturers of branded medicines, Roche has grown into the world’s largest biotechnology company and the global leader in in-vitro diagnostics. The company pursues scientific excellence to discover and develop medicines and diagnostics for improving and saving the lives of people around the world. We are a pioneer in personalised healthcare and want to further transform how healthcare is delivered to have an even greater impact. To provide the best care for each person we partner with many stakeholders and combine our strengths in Diagnostics and Pharma with data insights from the clinical practice. For over 125 years, sustainability has been an integral part of Roche’s business. As a science-driven company, our greatest contribution to society is developing innovative medicines and diagnostics that help people live healthier lives. Roche is committed to the Science Based Targets initiative and the Sustainable Markets Initiative to achieve net zero by 2045. Genentech, in the United States, is a wholly owned member of the Roche Group. Roche is the majority shareholder in Chugai Pharmaceutical, Japan. References [1] Turner NC, et al. Inavolisib-Based Therapy in PIK3CA-Mutated Advanced Breast Cancer. NEJM. 2024;391(17):1584-96. [2] Fillbrunn M, et al. PIK3CA mutation status, progression and survival in advanced HR+/HER2- breast cancer: a meta-analysis of published clinical trials. BMC Cancer. 2022;22:1002. [3] Anderson E, et al. A Systematic Review of the Prevalence and Diagnostic Workup of PIK3CA Mutations in HR+/HER2– Metastatic Breast Cancer. Int J Breast Cancer. 2020;2020:3759179. [4] ClinicalTrials.gov. A Study Evaluating the Efficacy and Safety of Inavolisib + Palbociclib + Fulvestrant vs Placebo + Palbociclib + Fulvestrant in Patients With PIK3CA-Mutant, Hormone Receptor-Positive, Her2-Negative, Locally Advanced or Metastatic Breast Cancer (INAVO120) [Internet; cited 2025 May]. Available from: https://classic.clinicaltrials.gov/ct2/show/NCT04191499. [5] ClinicalTrials.gov. A Study Evaluating the Efficacy and Safety of Inavolisib Plus Fulvestrant Compared With Alpelisib Plus Fulvestrant in Participants With HR-Positive, HER2-Negative, PIK3CA Mutated, Locally Advanced or Metastatic Breast Cancer Post CDK4/6i and Endocrine Combination Therapy (INAVO121) [Internet; cited 2025 May]. Available from: https://classic.clinicaltrials.gov/ct2/show/NCT05646862. [6] ClinicalTrials.gov. A Study to Evaluate the Efficacy and Safety of Inavolisib in Combination With Phesgo Versus Placebo in Combination With Phesgo in Participants With PIK3CA-Mutated HER2-Positive Locally Advanced or Metastatic Breast Cancer (INAVO122) [Internet; cited 2025 May]. Available from: https://classic.clinicaltrials.gov/ct2/show/NCT05894239. [7] ClinicalTrials.gov. A Study Evaluating the Efficacy and Safety of Inavolisib Plus CDK4/6 Inhibitor and Letrozole vs Placebo + CDK4/6i and Letrozole in Participants With Endocrine-Sensitive PIK3CA-Mutated, Hormone Receptor-Positive, HER2-Negative Advanced Breast Cancer (INAVO123) [Internet; cited 2025 April]. Available from: https://clinicaltrials.gov/study/NCT06790693. [8] Juric D, et al. A phase I/Ib study of inavolisib (GDC-0077) in combination with fulvestrant in patients (pts) with PIK3CA-mutated hormone receptor-positive/HER2-negative (HR+/HER2–) metastatic breast cancer. Presented at San Antonio Breast Cancer Symposium, 2020 December 7-10; San Antonio, USA. Abstract #P5-17-05. [9] Hong R, et al. GDC-0077 is a selective PI3K alpha inhibitor that demonstrates robust efficacy in PIK3CA mutant breast cancer models as a single agent and in combination with standard of care therapies. Cancer Res. 2018;78(4):4-14. [10] National Cancer Institute: Surveillance, Epidemiology and Ends Result Program. Cancer Stat Facts: Female Breast Cancer Subtypes [Internet; cited 2025 April]. Available from: https://seer.cancer.gov/statfacts/html/breast-subtypes.html. [11] Lim E, et al. The natural history of hormone receptor-positive breast cancer. Oncology (Williston Park). 2012;26(8):688-94,696. [12] Tomas R and Barrios CH. Optimal management of hormone receptor positive metastatic breast cancer in 2016. Ther Adv Med Oncol. 2015;7(6):304-20. [13] Galipeau N, et al. Understanding key symptoms, side effects, and impacts of HR+/HER- advanced breast cancer: qualitative study findings. J Patient-Rep Outcomes. 2019;3(1):10. The content above comes from the network. if any infringement, please contact us to modify.

Clinical ResultASCODrug Approval

100 Deals associated with Estrogens, Conjugated

External Link

KEGG	Wiki	ATC	Drug Bank
D04070	Estrogens, Conjugated	G03CA57	DB00286

R&D Status

Approved

10 top approved records.

to view more data

Indication	Country/Location	Organization	Date
Oestrogen deficiency	Australia	Pfizer Australia Pty Ltd.	28 May 2012
Dyspareunia	United States	Wyeth Pharmaceuticals LLC	07 Nov 2008
Osteoporosis	United States	Wyeth Pharmaceuticals LLC	16 Jul 2003
Breast Cancer	United States	Wyeth Pharmaceuticals LLC	24 Apr 2003
Hypoestrogenism	United States	Wyeth Pharmaceuticals LLC	24 Apr 2003
Prostatic Cancer	United States	Wyeth Pharmaceuticals LLC	24 Apr 2003
Vasomotor symptom	United States	Wyeth Pharmaceuticals LLC	24 Apr 2003
Vulvovaginal atrophy	China	Wyeth Canada ULC	07 Mar 2001
Atrophic Vaginitis	United States	Wyeth Pharmaceuticals LLC	16 Oct 1978
Atrophy	United States	Ayerst-Wyeth Pharmaceuticals, Inc.	16 Oct 1978
Vulvar Lichen Sclerosus	United States	Wyeth Pharmaceuticals LLC	16 Oct 1978
Andropause	Japan	Pfizer Japan, Inc.	15 Apr 1964
Metrorrhagia	Japan	Pfizer Japan, Inc.	15 Apr 1964
Ovarian Diseases	Japan	Pfizer Japan, Inc.	15 Apr 1964
Vaginitis	Japan	Pfizer Japan, Inc.	15 Apr 1964
Endocrine System Diseases	United States	Wyeth Pharmaceuticals LLC	18 Dec 1956
Osteoporosis, Postmenopausal	United States	Wyeth Pharmaceuticals LLC	08 May 1942
Vascular Diseases	United States	Ayerst-Wyeth Pharmaceuticals, Inc.	07 May 1942

Developing

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Menopausal symptoms	Phase 3	United States	Teva Branded Pharmaceutical Products R&D, Inc.	01 Aug 2006
Parkinson Disease	Phase 2	United States	Wyeth AB	01 Oct 2003
Amenorrhea	Phase 2	-	Abbott Laboratories	01 Sep 2000
Primary Ovarian Insufficiency	Phase 1	Japan	Pfizer Inc.	01 Oct 2011
Pelvic Organ Prolapse	Clinical	United States	Pfizer Inc.	01 May 2012
Uterine Prolapse	Clinical	United States	Pfizer Inc.	01 May 2012

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT01648751 (CTgov)	Not Applicable	Pelvic Organ Prolapse \| Uterine Prolapse	21	Vaginal estrogen (Vaginal Estrogen)	oasdqpqohr(wgyoddauhq) = rejlrkjfim csxufvrigq (vzmesdexjt, hathnfxesd - obovnzbzqp) View more	-	19 Sep 2024
				Placebo (Placebo Cream)	oasdqpqohr(wgyoddauhq) = ijywuzktrf csxufvrigq (vzmesdexjt, dgvtgskrkn - ucsozcttrc) View more
EULAR2024	Not Applicable	Rheumatoid Arthritis	-	oestrogen (Premenopausal women)	nrcuegrznb(xklguuduzd): HR = 2.8 (95% CI, 1.2 - 6.4)	-	05 Jun 2024
				oestrogen (Postmenopausal women)
NCT03943823 (CTgov)	Phase 4	Vaginal Discharge \| Bacterial Vaginosis	4	Premarin+Estrace (Estrogen Vaginal Cream)	zaxgrbzmnx(odkxaznzfh) = gcdyvewjby qpflubsoqe (fdlwtttlwm, 0.70) View more	-	01 Mar 2023
				Trimo-San (Trimo-San Vaginal Gel)	zaxgrbzmnx(odkxaznzfh) = dmmlfmanaq qpflubsoqe (fdlwtttlwm, 0) View more
NCT01958073 (VESPR, CTgov)	Phase 4	Urinary Tract Infections	35	Placebo (Placebo)	caxkpffmun = guibwefeez bhmphejjbg (hmjjakgrmi, kvdrmcabpb - bnspumagum) View more	-	21 Sep 2020
				Conjugated Estrogen Vaginal Cream (Conjugated Estrogen Vaginal Cream)	rsobaupciy = pkpvqqnaek cmusvuvtpo (qgcnvsbpkm, swfbdjgblq - qlleqppezh) View more
NCT00973102 (RESCUE-Shock \| RESCUE - Shock, CTgov)	Phase 2	Shock, Hemorrhagic \| Shock	50	Premarin IV (Premarin IV)	tewyhesrvh = hhmmehgumx gggsrggkbj (uoomipgror, xyeqxwpsqn - yinvcgpscz) View more	-	19 Mar 2020
				Placebo (Placebo)	tewyhesrvh = onwttsyodv gggsrggkbj (uoomipgror, wkhstcsbxu - hsnhsijnkv) View more
NCT00973674 (RESCUE-TBI, CTgov)	Phase 2	Brain Injuries, Traumatic	50	Premarin IV (Premarin IV)	uccpdmjnkk = apkehjhoor mmqwyswsoq (pnoqqkphmk, vknxoozfyt - ecfhkqepgg) View more	-	12 Nov 2019
				Placebo (Placebo)	uccpdmjnkk = fefordfhjh mmqwyswsoq (pnoqqkphmk, vokbdvyxzr - lvbftckeiy) View more
MON-160 (ENDO2019)	Not Applicable	Obesity leptin \| adiponectin \| FGF-21 ... View more	12	Conjugated Estrogens/Bazedoxifene	kamigqjurl(qpfmhkmgjq) = vdtayrtfkl zxiiaibkec (lqhwdwqdpc, 3.1) View more	Positive	30 Apr 2019
				Placebo	kamigqjurl(qpfmhkmgjq) = ddmxfwjzvs zxiiaibkec (lqhwdwqdpc, 2.9) View more
NCT01268046 (CTgov)	Phase 1/2	Amnesia	38	Estradiol+transderman estrogen patch (Young Postmenopausal Women - Estrogen)	pvedbbyioa(mgyivmlryu) = ehhlvifbbh svkihkvaha (xousaoxjpg, 164.3) View more	-	22 Aug 2018
				Estradiol+transderman estrogen patch (Older Postmenopausal Women - Estrogen)	pvedbbyioa(mgyivmlryu) = pysszxuzej svkihkvaha (xousaoxjpg, 90.1) View more
NCT00604825 (CTgov)	Phase 2	Menopausal symptoms \| Hot Flashes \| Vasomotor symptom ... View more	356	Other: Placebo	qrajigbxut = tusapswqog dfkoikegrk (czmicoqyln, jcojhrnzhc - wnwoayekqg) View more	-	03 Oct 2017
NCT00386022 (CTgov)	Phase 2/3	-	19	GnRH+Estrogen patch (Young Postmenopausal Women)	ajyprqnfhg(rhhhcmcekq) = zeoqywtjbf watkpegfky (pczzfxjzsz, 1.9) View more	-	13 Apr 2017
				GnRH+Estrogen patch (Older Postmenopausal Women)	ajyprqnfhg(rhhhcmcekq) = hocwhmfcxh watkpegfky (pczzfxjzsz, 1.0) View more

Translational Medicine

Boost your research with our translational medicine data.

view full example data

Deal

Boost your decision using our deal data.

view full example data

Core Patent

Boost your research with our Core Patent data.

view full example data

Clinical Trial

Identify the latest clinical trials across global registries.

view full example data

Approval

Accelerate your research with the latest regulatory approval information.

view full example data

Regulation

Understand key drug designations in just a few clicks with Synapse.

view full example data

AI Agents Built for Biopharma Breakthroughs

Accelerate discovery. Empower decisions. Transform outcomes.

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Empower better decisions with the latest in pharmaceutical intelligence.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis

Estrogens, Conjugated

Overview

Basic Info

Related

External Link

R&D Status

Clinical Result

Translational Medicine

Deal

Core Patent

Clinical Trial

Approval

Regulation