ESR1 Mutated Metastatic Breast Cancer - Market Insight, Epidemiology And Market Forecast - 2032

Key Highlights

• ESR1 mutations rarely exist in primary tumors (~1%) but are relatively common (10-50%) in metastatic, endocrine therapy-resistant cancers and are associated with shorter progression-free survival.
• In 2022, the market size of ESR1-mutated Metastatic Breast Cancer was the highest in the US among the 7MM, accounting for approximately USD 800 million, which is further expected to increase by 2032.
• ORSERDU (elacestrant) is the first endocrine innovation in 20 years specifically targeting ESR1 mutations in ER+, HER2-, advanced, or metastatic breast cancer patients with disease progression following at least one line of endocrine therapy
• The emergence of several novel selective estrogen receptor degraders (SERDs) in the ESR1 space has demonstrated a widespread potential for this patient population in combination and as monotherapy.
• There is a need for new endocrine therapy (ET) agents with strong and durable activity in heavily treated patients, including after standard-of-care first-line therapy with CDK4/6 inhibitors and in those with ESR1 mutations.
• Key players like AstraZeneca (Camizestrant), Eli Lilly and Company (Imlunestrant), H3 Biomedicine (H3B-6545), Roche (Giredestrant), Arvinas (ARV-471), Sermonix Pharmaceuticals (Lasofoxifene), Olema Pharmaceuticals (OP-1250), and others are evaluating their lead candidates in different lines of therapies and different stages of clinical development, respectively. These companies can potentially create a significant shift in the ESR1 market size.

This “ESR1-mutated Metastatic Breast Cancer - Market Insights, Epidemiology, and Market Forecast - 2032 report delivers an in-depth understanding of the disease, historical and forecasted epidemiology as well as the market trends in the United States, EU4 (Germany, Spain, Italy, and France) and the United Kingdom, and Japan.

The ESR1-mutated Metastatic Breast Cancer market report provides current treatment practices, emerging drugs, market share of individual therapies, and current and forecasted 7MM market size from 2019 to 2032. The report also covers current treatment practices/algorithms and unmet medical needs to curate the best opportunities and assess the market's potential.

Geography Covered

• The United States
• EU4 (Germany, France, Italy, and Spain) and the United Kingdom
• Japan

Study Period: 2019-2032

ESR1-mutated Metastatic Breast Cancer Disease Understanding and Treatment Algorithm

ESR1-mutated Metastatic Breast Cancer Overview

In metastatic hormone receptor-positive breast cancer, ESR1 mutations commonly cause acquired resistance to the backbone of therapy and estrogen deprivation by aromatase inhibition. ESR1 mutations rarely occur in primary breast cancer but have a high prevalence in advanced breast cancers previously treated with aromatase inhibitors implying evolution through selective treatment pressure. Most ESR1 mutations occur in hotspot regions in the ligand-binding domain of ER, resulting in ligand-independent, constitutive ER activity. Prior research has demonstrated that circulating tumor DNA (ctDNA) is detected in the plasma of patients with cancer and may provide a robust, noninvasive method for detecting ESR1 mutation.

ESR1-mutated Metastatic Breast Cancer Diagnosis

The patient's journey begins with initial symptoms of breast cancer, such as pain in the nipple area, nipple discharge other than milk, a new lump in the breast or underarm, and swelling of the part of the breast. Followed by a visit to the Gynecologist/Oncologist. Where the patient is suggested diagnostic tests such as MRI, clinical breast exam, and mammogram. After the diagnosis patient is referred to an oncologist for further treatment. A Breast ultrasound, diagnostic mammogram, and tissue biopsy is performed by imaging for confirmatory diagnosis. Once ESR1 is confirmed, relevant treatment is given to the patient.

ESR1-mutated Metastatic Breast Cancer Treatment

Much progress has been accomplished in treating hormone receptor-positive (HR+) breast cancer and the survival rate of individuals with the illness over the past decade; however, acquired resistance to endocrine-based therapy remains a concern. The recent identification of treatment-resistant ESR1 mutations has generated interest in developing new estrogen receptor-targeting medicines, such as orally accessible selective estrogen receptor degraders (SERDs), to overcome fulvestrant's effectiveness constraints potentially.

Clinically, patients with ESR1 mutations derive clinical benefits when treated with fulvestrant, and CDK4/6 targeted therapies. Still, developing more potent selective estrogen receptor degraders (SERDs) and/or new targeted biotherapies is needed to overcome the endocrine-resistant phenotype of ESR1 mutant-bearing tumors.

Current treatment guidelines for ER-positive Metastatic Breast Cancer do not stratify patients based on ESR1 mutation status. However, many preclinical studies have demonstrated that ESR1 mutant cells respond to fulvestrant.

ESR1-mutated Metastatic Breast Cancer Epidemiology

The market is derived using a patient-based model, and the epidemiology chapter in the report provides historical as well as forecasted epidemiology segmented by total diagnosed prevalent cases of HR-positive Breast Cancer, total diagnosed prevalent cases of ESR1-mutated Metastatic Breast Cancer, stage-specific diagnosed prevalent cases of HR+ Breast Cancer, total diagnosed prevalent cases of Metastatic Breast Cancer, in the 7MM covering the United States, EU4 countries (Germany, France, Italy, and Spain), United Kingdom, and Japan from 2019 to 2032. The total diagnosed prevalent cases of ESR1-mutated Metastatic Breast Cancer in the 7MM comprised approximately 43,000 cases in 2022 and are projected to increase during the forecasted period.

• Out of all the stage specific cases, majority of the patients fall under localized and regional stages of Breast Cancer. ESR1 mutations exclusively occurs in HR+ positive patients after an aromatase inhibitor in the metastatic setting.
• The total diagnosed prevalent cases of ESR1-mutated Metastatic Breast Cancer in the United States was around 19,000 cases in 2022.
• The diagnosed prevalent cases of ESR1-mutated HR+ Metastatic Breast Cancer on first-line of treatment in the United States was estimated to be around 18,000 in 2022.
• Among the EU4 countries, Germany had the highest cases of ESR1 mutation in metastatic breast cancer, followed by France, whereas Spain accounted for the lowest number of cases in 2022.
• According to the publisher's estimates, Japan reported approximately 45,000 cases of metastatic breast cancer, equivalent to around 13% of total cases in the 7MM.
• According to the publisher's estimates, the total diagnosed prevalent cases of ESR1-mutated metastatic breast cancer in Japan was approximately 5,000, and these cases are expected to increase during the study period.

ESR1-mutated Metastatic Breast Cancer Drug Chapters

The drug chapter segment of the report encloses a detailed analysis of the late-stage (Phase II) pipeline drug. Currently, there is one approved therapy for ESR1 mutated Metastatic Breast Cancer. It also helps understand the clinical trial details, expressive pharmacological action, agreements and collaborations, approval and patent details, advantages and disadvantages of each included drug, and the latest news and press releases.

Marketed Drug
ORSERDU (elacestrant): Stemline Therapeutics (a wholly owned subsidiary of the Menarini Group)
ORSERDU (elacestrant) is a selective estrogen receptor degrader (SERD) out-licensed to Menarini Group. In January 2023, the US FDA approved ORSERDU for treating postmenopausal women or adult men with ER+, HER2-, ESR1-mutated, advanced or metastatic breast cancer with disease progression following at least one line of endocrine therapy. Moreover, the Marketing Authorization Application (MAA) is currently under review by the European Medicines Agency (EMA).

ORSERDU is the first next generation SERD to get an approval in this indication, therefore making way for several other players developing SERD or SERM. The novel SERD functions by degrading ERa and inhibiting estradiol-dependent estrogen receptor-related gene transcription and tumor growth with improved pharmacological properties compared to fulvestrant.

Emerging Drug

Camizestrant (AZD9833): AstraZeneca

Camizestrant (AZD9833) is an oral SERD that has shown antitumor efficacy in a range of preclinical models of breast cancer. In June 2020, AstraZeneca initiated a Phase III clinical trial, SERENA-6, to evaluate the safety and efficacy of AZD9833 in combination with a CDK4/6 inhibitor (palbociclib or abemaciclib) for the treatment of patients with HR+ HER2- metastatic breast cancer with a detectable ESR1 mutation. As per Astrazeneca's pipeline, Camizestrant's + CDK4/6 inhibitor's estimated filing acceptance in 1st line HR+ HER2- ESR1m breast cancer is 2024. Apart from that, the indication for SERENA-6 has been granted Fast Track Designation (FTD) by the US FDA.

Lasofoxifene: Sermonix Pharmaceuticals

Lasofoxifene is being investigated as a potent, bioavailable selective estrogen receptor modulator (SERM - also known as an estrogen agonist/antagonist) with a differentiated safety profile that could prove useful in treating postmenopausal women and premenopausal women on ovarian suppression with locally advanced or metastatic ER+ breast cancer. Lasofoxifene's bioavailability and activity in estrogen receptor mutations could hold promise for patients who have acquired endocrine resistance due to ESR1 mutations, a common finding in the metastatic setting and an area of high unmet medical needs need. The drugs' novel activity in ESR1 mutations was discovered at Duke University, and Sermonix has exclusive rights to develop and commercialize the product in this area. Lasofoxifene, if approved, could play a critical role in the targeted precision medicine treatment of advanced ER+ breast cancer. Lasofoxifene has demonstrated preclinical antitumor activity in ESR1-mutant models and is currently being investigated in different clinical trials. The Phase II ELAINE trial (NCT03781063) explores lasofoxifene vs. fulvestrant in female patients with advanced luminal BC with ESR1 mutations. In May 2019, the US FDA granted lasofoxifene FTD to treat women who have ER+ metastatic breast cancer with an ESR1 mutation.

Note: Detailed emerging therapies assessment will be provided in the final report.

Drug Class Insights

The existing ESR1 treatment is mainly dominated by classes such as aromatase inhibitors, aromatase inhibitors + CDK4/6 inhibitors, and CDK4/6 + SERDs.

For postmenopausal women with HR-positive, HER2-positive recurrent/Stage IV breast cancer, the preferred options available include fulvestrant with a CDK 4/6 inhibitor (palbociclib, ribociclib, and abemaciclib; category 1) or for those with tumor PIK3CA mutations, fulvestrant with alpelisib; everolimus with either an AI, tamoxifen or fulvestrant; monotherapy with fulvestrant, nonsteroidal or steroidal AI, or SERM. Estrogen receptor 1 (ESR1) activating mutations are frequently detected in patients with prior exposure to AIs. Tumors with these mutations are generally resistant to both AIs and tamoxifen. Certain tumors with these mutations retain sensitivity to fulvestrant. All may benefit from adding a CDK 4/6 inhibitor, mTOR-inhibitor, or alpelisib in combination with fulvestrant if the tumor has PIK3CA mutation.

Moreover, the upcoming treatment landscape is poised to expand after new classes, such as next-generation SERDs and SERMs. With the approval of the first SERD, it can be anticipated that the upcoming SERDs can give us more options and expand the horizon of the treatment paradigm along a different line of therapy.

ESR1-mutated Metastatic Breast Cancer Market Outlook

ESR1 mutations have increased, even with aromatase inhibitor (AI) therapy, indicating their adaptability to AI therapeutic conditions. In addition, the presence of ESR1 mutations has been correlated with a shorter time to treatment failure, as metastatic breast cancer (MBC) patients with ESR1 mutations exhibit an inadequate response to and shorter duration of effective endocrine control. Suppose AI treatment provides selection pressure for mutant-bearing clonal outgrowth in patients. In that case, the next option for therapy is likely a more effective selective estrogen receptor modulator (SERMs) and/or selective estrogen receptor downregulators (SERDs). Various studies have predicted that ESR1 mutations will still respond to SERMs or SERDs, though perhaps at a decreased sensitivity based on in vitro, xenograft, and PDX preclinical models. In the past 5 years, agents that have become available are CDK4/6 inhibitors.

Fulvestrant at 500 mg prevents progression in ER mutant-bearing tumors more effectively. This indicates that high-dose fulvestrant may be a promising therapeutic option. It also highlights the need to develop novel, more potent SERMs/SERDs.

Combinations of fulvestrant and other endocrine treatments have not shown a clear advantage over single-agent therapy. However, fulvestrant might offer some advantages compared to other endocrine treatments as an endocrine backbone of combination therapy, most notably the ability to overcome ESR1 mutations that might be seen in patients who have relapsed on or after adjuvant aromatase inhibitors. The majority of patients prefer oral therapy as compared to injectable therapy. However, the drawback of long-term oral endocrine therapy is the lack of treatment adherence.

The current market has been segmented into different commonly used therapeutic classes based on the prevailing treatment pattern across the 7MM, which presents minor variations in the overall prescription pattern. Aromatase inhibitor + CDK4/6 inhibitor, CDK4/6 + Fulvestrant, and others are covered in the forecast model.

The expected launch of upcoming therapy and greater integration of early patient screening, medication in secondary care and other clinical settings, research on best methods for implementation, and an upsurge in awareness will eventually facilitate the development of effective treatment options. However, it would be great to have an endocrine therapy that could work regardless of the presence of an ESR1 mutation.

• The total market size of ESR1-mutated Metastatic Breast Cancer in the 7MM is approximately USD 1,300 million in 2022 and is projected to increase during the forecast period (2023-2032).
• According to the publisher's estimates, the US accounted for the maximum share of the total market in the 7MM, i.e., around 63%, followed by EU4 and the UK combined, capturing nearly 29% share in 2022.
• Among EU4 countries, Germany accounts for the maximum market size in 2022, while Spain occupies the bottom of the ladder.
• In the United States, aromatase inhibitor + CDK4/6 inhibitor is expected to garner the highest market share in the first-line setting, with a revenue of approximately USD 300 million.
• Key therapies with Fast track designation (FTD) for ESR1 mutation includes Camizestrant, Lasofoxifene and OP-1250

ESR1-mutated Metastatic Breast Cancer Drugs Uptake

This section focuses on the uptake rate of potential drugs expected to be launched in the market during 2019-2032. For example, for Camizestrant (AZD9833) + Palbociclib, we expect the drug uptake to be medium with a probability-adjusted peak share of 10% in the first line setting. Considering that the Phase III trial efficacy data for first line setting is not yet available the probability of success is not on a higher end.

Further detailed analysis of emerging therapies drug uptake in the report.

ESR1-mutated Metastatic Breast Cancer Pipeline Development Activities

The report provides insights into different therapeutic candidates in Phase III, Phase II, and Phase I stage. It also analyzes key players involved in developing targeted therapeutics.

Pipeline Development Activities

The report covers information on collaborations, acquisitions and mergers, licensing, and patent details for ESR1-mutated Metastatic Breast Cancer emerging therapy.

KOL Views

To keep up with current market trends, we take KOLs and SMEs' opinions working in the domain through primary research to fill the data gaps and validate our secondary research. Industry Experts contacted for insights on ESR1 mutated Metastatic Breast Cancer evolving treatment landscape, patient reliance on conventional therapies, patient's therapy switching acceptability, and drug uptake along with challenges related to accessibility, including Medical/scientific writers; Medical Oncologists; Gynecologist and Professors; MD, PhD, of Breast medical oncologist and chief of the division of breast oncology at Dana Farber Cancer Institute, Director of Breast Cancer Research at Mass General Cancer Center, and Others.

This analysts connected with 30+ KOLs to gather insights; however, interviews were conducted with 10+ KOLs in the 7MM. Centers such as MD Anderson Cancer Center, Breast oncology nurse practitioner, Cancer Research UK Barts Centre in London, MD Anderson Cancer Center, etc., were contacted. Their opinion helps understand and validate current and emerging therapy treatment patterns, or ESR1 mutated Metastatic Breast Cancer market trends. This will support the clients in potential upcoming novel treatments by identifying the overall scenario of the market and the unmet needs.

Qualitative Analysis

The publisher performs Qualitative and market Intelligence analysis using various approaches, such as SWOT analysis and Analyst views. In the SWOT analysis, strengths, weaknesses, opportunities, and threats in terms of disease diagnosis, patient awareness, patient burden, competitive landscape, cost-effectiveness, and geographical accessibility of therapies are provided. These pointers are based on the analyst's discretion and assessment of the patient burden, cost analysis, and existing and evolving treatment landscape.

The analyst views analyze multiple emerging therapies based on relevant attributes such as safety, efficacy, designation, and order of entry.

In efficacy, the trial's primary and secondary outcome measures are evaluated; for instance, in ESR1 trials, one of the most important primary outcome measures is progression-free survival.

Further, the therapies' safety is evaluated wherein the acceptability, tolerability, and adverse events are majorly observed, and it sets a clear understanding of the side effects posed by the drug in the trials.

Market Access and Reimbursement

Reimbursement of rare disease therapies can be limited due to lack of supporting policies and funding, challenges of high prices, lack of specific approaches to evaluating rare disease drugs given limited evidence, and payers' concerns about budget impact. The high cost of rare disease drugs usually has a limited impact on the budget due to the small number of eligible patients being prescribed the drug. The US FDA has approved several rare disease therapies in recent years. From a patient perspective, health insurance and payer coverage guidelines surrounding rare disease treatments restrict broad access to these treatments, leaving only a small number of patients who can bypass insurance and pay for products independently.

The report further provides detailed insights on the country-wise accessibility and reimbursement scenarios, cost-effectiveness scenario of approved therapies, programs making accessibility easier and out-of-pocket costs more affordable, insights on patients insured under federal or state government prescription drug programs, etc.

Scope of the Report

• The report covers a segment of key events, an executive summary, descriptive overview of ESR1 mutated Metastatic Breast Cancer, explaining its causes, signs and symptoms, pathogenesis, and currently available therapies.
• Comprehensive insight into the epidemiology segments and forecasts, disease progression, and treatment guidelines has been provided.
• Additionally, an all-inclusive account of the current and emerging therapies, along with the elaborative profiles of late-stage and prominent therapies, will impact the current treatment landscape.
• A detailed review of the ESR1-mutated Metastatic Breast Cancer market, historical and forecasted market size, market share by therapies, detailed assumptions, and rationale behind our approach is included in the report, covering the 7MM drug outreach.
• The report provides an edge while developing business strategies, by understanding trends, through SWOT analysis, expert insights/KOL views, patient journey, and treatment preferences that help shape and drive the 7MM ESR1-mutated Metastatic Breast Cancer market.

ESR1 mutated Metastatic Breast Cancer Report Insights

• Patient Population
• Therapeutic Approaches
• ESR1-mutated Metastatic Breast Cancer Pipeline Analysis
• ESR1-mutated Metastatic Breast Cancer Market Size and Trends
• Existing and future Market Opportunity

ESR1-mutated Metastatic Breast Cancer Report Key Strengths

• Ten years Forecast
• 7MM Coverage
• ESR1-mutated Metastatic Breast Cancer Epidemiology Segmentation
• Key Cross Competition
• Conjoint Analysis
• Drugs Uptake and Key Market Forecast Assumptions

ESR1-mutated Metastatic Breast Cancer Report Assessment

• Current Treatment Practices
• Unmet Needs
• Pipeline Product Profiles
• Market Attractiveness
• Qualitative Analysis (SWOT and Analyst Views)

Key Questions Answered

Market insights

• What was the ESR1-mutated Metastatic Breast Cancer total market size, the market size by therapies, market share (%) distribution in 2019, and what would it look like in 2032? What are the contributing factors for this growth?
• Which class is going to be the largest contributor in 2032?
• Are Next generation SERD's better than off-label Faslodex?
• What will be the impact of Camizestrant (AZD9833) + palbociclib after its expected approval in 2025 in the first-line setting?
• What are the pricing variations among different geographies for approved and off-label therapies?
• How would the market drivers, barriers, and future opportunities affect the market dynamics and subsequent analysis of the associated trends?

Epidemiology Insights:

• What are the disease risk, burdens, and unmet needs of ESR1 mutated Metastatic Breast Cancer? What will be the growth opportunities across the 7MM with respect to the patient population pertaining to ESR1-mutated Metastatic Breast Cancer?
• What is the biomarker testing rate among this patient pool?
• What is the historical and forecasted ESR1-mutated Metastatic Breast Cancer patient pool in the United States, EU4 (Germany, France, Italy, and Spain), the United Kingdom, and Japan?
• Why do only limited patients appear with symptoms? Why is the current year diagnosis rate not high?

Current Treatment Scenario, Marketed Drugs, and Emerging Therapies:

• What are the current options for the treatment of ESR1-mutated Metastatic Breast Cancer? What are the current guidelines for treating ESR1-mutated Metastatic Breast Cancer in the US and Europe?
• How many companies are developing therapies for treating ESR1-mutated Metastatic Breast Cancer?
• How many emerging therapies are in the mid-stage and late stage of development for treating ESR1-mutated Metastatic Breast Cancer?
• What are the recent novel therapies, targets, mechanisms of action, and technologies being developed to overcome the limitation of existing therapies?
• What key designations have been granted for the emerging therapies for ESR1-mutated Metastatic Breast Cancer?
• What will be the impact of Camizestrant (AZD9833) + palbociclib expected entry for the first-line ESR1 patient pool?
• What is the cost burden of current therapies on the patient?
• Patient acceptability in terms of preferred treatment options as per real-world scenarios?
• What are the country-specific accessibility issues of expensive, current therapies? Focusing on the reimbursement policies.
• What is the 7MM historical and forecasted market of ESR1-mutated Metastatic Breast Cancer?

Reasons to Buy

• The report will help develop business strategies by understanding the latest trends and changing treatment dynamics driving the ESR1-mutated Metastatic Breast Cancer Market.
• Insights on patient burden/disease incidence, evolution in diagnosis, and factors contributing to the change in the epidemiology of the disease during the forecast years
• Understand the existing market opportunity in varying geographies and the growth potential over the coming years.
• Distribution of historical and current patient share based on real-world prescription data along with reported sales of approved products in the US, EU4 (Germany, France, Italy, and Spain), the United Kingdom, and Japan.
• Identifying strong upcoming players in the market will help devise strategies to help get ahead of competitors.
• Detailed analysis and ranking of class-wise potential current and emerging therapies under the analyst view section to provide visibility around leading classes.
• Highlights of access and reimbursement policies of approved therapies, barriers to accessibility of expensive off-label therapies, and patient assistance programs.
• To understand key opinion leaders' perspectives around the accessibility, acceptability, and compliance-related challenges of existing treatment to overcome barriers in the future.
• Detailed insights on the unmet need of the existing market so that the upcoming players can strengthen their development and launch strategy.