PUBLISHER: DelveInsight | PRODUCT CODE: 1376845
PUBLISHER: DelveInsight | PRODUCT CODE: 1376845
DelveInsight's "Metastatic HR+/HER2- Breast Cancer - Market Insights, Epidemiology, and Market Forecast-2032" report delivers an in-depth understanding of the HR+/HER2- Breast Cancer, historical and forecasted epidemiology as well as the HR+/HER2- breast cancer market trends in the United States, EU4 (Germany, Spain, Italy, and France) and the United Kingdom, and Japan.
The HR+/HER2- breast cancer market report provides current treatment practices, emerging drugs, HR+/HER2- breast cancer market share of the individual therapies, and current and forecasted HR+/HER2- breast cancer market size from 2019 to 2032 segmented by seven major markets. The report also covers current HR+/HER2- breast cancer treatment practices/algorithms, and unmet medical needs to curate the best of the opportunities and assesses the underlying potential of the market.
Study Period: 2019-2032.
HR+/HER2- breast cancer is the most common subtype of breast cancer, characterized by cancer cells with hormone receptors for estrogen and progesterone but lacking the overexpression of HER2. This subtype generally has a better prognosis and is often treated with hormone therapy to block hormone-driven growth. Surgery and radiation may be used to remove or target tumors, while chemotherapy and targeted therapies like CDK4/6 inhibitors may be considered for more advanced cases. Early detection is crucial, and support from healthcare providers and loved ones is vital for coping with the diagnosis and treatment of HR+/HER2- breast cancer.
A patient's journey through HR+/HER2- breast cancer diagnosis typically begins with the recognition of concerning symptoms, leading to clinical evaluation and imaging tests. A biopsy confirms the diagnosis and determines the cancer's characteristics. Staging tests assess the cancer's extent, guiding a multidisciplinary team in devising a personalized treatment plan, often involving hormone therapy, surgery, radiation, and possibly chemotherapy or targeted therapies. Emotional support plays a crucial role in managing the emotional toll of the diagnosis, and follow-up care ensures ongoing monitoring and adjustment of treatment as needed, fostering hope for successful recovery and survivorship.
The treatment of HR+/HER2- breast cancer typically involves a multimodal approach. Hormone therapy is a cornerstone, blocking estrogen's effects on cancer cells. Surgery, such as lumpectomy or mastectomy, may be performed to remove the tumor. Radiation therapy targets any remaining cancer cells after surgery. In more advanced cases, chemotherapy or targeted therapies like CDK4/6 inhibitors can be considered. The specific treatment plan depends on factors like cancer stage, receptor status, and patient preferences. Regular follow-up and monitoring are essential to track progress and adjust treatment as needed, offering the best chance for successful management and long-term survival.
A number of classes of anti-estrogenic agents available for patients with early, advanced, or metastatic breast cancer which includes selective estrogen receptor modulators (SERMs), aromatase inhibitors (AIs), and a selective estrogen receptor degrader. However, the clinical development of combinations of antiestrogenic therapy with targeted agents that inhibit the phosphatidylinositol 3 kinase (PI3K)/AKT murine thymoma viral oncogene (AKT)/mammalian target of rapamycin inhibitor (mTOR) signalling pathway or the cyclin-dependent kinase 4/6 (CDK4/6) pathway at the G1/S checkpoint of the cell cycle is currently a key focus of clinical research in patients with hormone-receptor positive breast cancer who have demonstrated disease recurrence or progression.
The HR+/HER2- Breast Cancer epidemiology chapter in the report provides historical as well as forecasted epidemiology segmented by total incidence of breast cancer, incident cases of HR+/HER2- breast cancer, menopausal status of HR+/HER2- breast cancer, stage-specific cases of HR+/HER2- breast cancer, age-specific cases of HR+/HER2- breast cancer and treatment-eligible Pool for HR+/HER2- Breast Cancer in the 7MM covering the United States, EU4 (Germany, France, Italy, and Spain), United Kingdom, and Japan from 2019 to 2032.
The drug chapter segment of the HR+/HER2- Breast Cancer report encloses a detailed analysis of the marketed and late-stage (Phase III) pipeline drug. The marketed drugs segment encloses drugs such as KISQALI (Novartis), PIQRAY (Daiichi Sankyo/AstraZeneca), IBRANCE (Pfizer), and others. Furthermore, the current key players for the upcoming emerging drugs and their respective drug candidates include ARV-471 (Arvinas), OP1250 (Olema Pharmaceuticals), Capivasertib (AstraZeneca) and others. The drug chapter also helps understand the HR+/HER2- Breast Cancer clinical trial details, expressive pharmacological action, agreements and collaborations, approval and patent details, and the latest news and press releases.
Novartis is committed to continuing to study KISQALI in breast cancer. NATALEE is a large Phase III clinical trial of KISQALI with endocrine therapy in the adjuvant treatment of HR+/HER2- early breast cancer being conducted in collaboration with Translational Research in Oncology (TRIO). Additionally, Novartis is collaborating with the Akershus University Hospital in Norway on the NEOLETRIB trial, a neoadjuvant Phase II trial studying the effects of KISQALI in HR+/HER2- early breast cancer and to discover the potentially unique underlying mechanism of action. Novartis also plans to build on the findings from ADJUVANT WIDER, an open-label Phase IIIb trial evaluating KISQALI plus ET in a population of HR+/HER2- patients with Stage II and III EBC (early breast cancer) that is closer to a real-world population.
PIQRAY is an orally bioavailable, alpha-specific PI3K inhibitor developed by Novartis. In breast cancer cell lines harboring PIK3CA mutations, BYL719 has been shown to inhibit the PI3K pathway potentially and have antiproliferative effects. In addition, cancer cell lines with PIK3CA mutations were also more sensitive to BYL719 than those without the mutation across a broad range of cancers.
In vivo, alpelisib inhibited the PI3K/AKT signaling pathway and reduced tumor growth in xenograft models, including models of breast cancer. PI3K inhibition by alpelisib treatment has increased estrogen receptor (ER) transcription in breast cancer cells. The combination of alpelisib and fulvestrant demonstrated increased antitumor activity compared to either treatment alone in xenograft models derived from ER+ and PIK3CA mutated breast cancer cell lines.
ARV-471 is an investigational, oral PROTAC estrogen receptor protein degrader for the treatment of patients with estrogen receptor (ER) positive/human epidermal growth factor receptor 2 (HER2) negative (ER+/HER2-) locally advanced or metastatic breast cancer. Arvinas and Pfizer are collaborating to develop and commercialize vepdegestrant. This program is currently in Phase III clinical studies.
In the first quarter of 2023, Arvinas and Pfizer requested a meeting with the US Food and Drug Administration, or the FDA, to review the proposed update to the trial protocol for the VERITAC-3 first-line, metastatic ER+/HER2- breast cancer Phase III trial of ARV-471 in combination with IBRANCE (palbociclib) to determine the optimal dose of palbociclib as part of the trial design.
OP-1250 is a small molecule complete estrogen receptor antagonist (CERAN). OP-1250 competes with the endogenous activating estrogenic ligand 17-beta estradiol for binding in the ligand-binding pocket. OP-1250 blocks estrogen-driven transcriptional activity inhibits estrogen-driven breast cancer cell growth, and induces degradation of the estrogen receptor.
The company is advancing OP-1250 toward pivotal Phase III studies. In addition to that, the pivotal Phase III study in 2/3L is planned to be initiated in mid-2023. The pivotal Phase III combination study with CDK 4/6i is expected to be initiated by 2024.
Detailed emerging therapies assessment will be provided in the final report.
The emergence of several novel CDK4/6 inhibitors in the ER+/HER2-breast cancer space has demonstrated widespread potential for this patient population in combination and as monotherapy. Moreover, the upcoming SERDS could also muscle its way into this treatment space for this patient pool. The other therapies include AKT inhibitors, mTOR inhibitors, SERMS, PI3K inhibitors, and TROP-2 targeting antibody-drug conjugate.
Cyclin-dependent kinase (CDK) inhibitors, the newest class of interest for advanced breast cancer, work by specifically inhibiting CDK4/6 proteins and blocking the transition from the G1 to the S phase of the cell cycle. This drug class inhibits kinase activity, which phosphorylates the retinoblastoma protein pathway. By blocking this path, CDK4/6 inhibitors are able to block cell-cycle progression in the middle of the G1 phase and prevent cancer cell progression. The approved CDK4/6 inhibitors have already gained a higher revenue than mTOR protein inhibitors, followed by SERDS and other therapies. Three CDK4/6 inhibitors (palbociclib, ribociclib, and abemaciclib) have been approved as combination therapies for HR+, human epidermal growth factor receptor 2-negative (HER2-), advanced or metastatic breast cancers.
The benefit of SERD over SOC ET appears to be more pronounced in patients with endocrine-sensitive tumors harboring ESR1 mutations without significant activation of other pathways. Recently, in January 2023, the FDA approved an oral SERD elacestrant (ORSERDU) for postmenopausal women or adult men with ER + /HER2-, ESR1-mutated ABC after progression on at least one line of ET. Ocular or cardiac toxicities reported with other SERDs, SERMs, or SERCAs, such as giredestrant, camizestrant, and tamoxifen, were not observed with elacestrant. Compared with the other SERDS, Giredestrant (SERD) has witnessed disappointment in its Phase II acelERA study but showed some promise in ESR1 mutation. Roche is conducting another Phase III trial for evaluating giredestrant + everolimus for ER+ HER2- mBC.
Approximately 40% of HR+ and HER2- breast cancers harbor an activating mutation in PIK3CA.The gene product of PIK3CA is phosphatidylinositol 3-kinase (PI3K), a tyrosine kinase and key component of the PI3K and protein kinase B (AKT) pathway that regulates cell growth. Dysregulation of the PI3K and AKT pathway occurs in several subtypes of breast cancer, and although degree of pathway activation may be highest in triple-negative breast cancers, the incidence of these mutations is most common in HR+ and HER2- breast cancers. Alpelisib, in combination with fulvestrant, is approved by the US FDA for PIK3CA-mutated advanced HR+ and HER2-breast cancer based on SOLAR-1.
For the past decade, endocrine therapy has been the preferred treatment for HR-positive and HER2- metastatic breast cancer, including cases with visceral involvement. This therapy, encompassing antiestrogens and aromatase inhibitors (AIs), remains the primary systemic approach for HR+/HER2- metastatic breast cancer due to its favorable treatment profile. Currently, there are three AIs available: anastrozole and letrozole are nonsteroidal AIs, while exemestane is a steroidal AI. Combining endocrine therapy with targeted agents, such as CDK 4/6 inhibitors or mTOR inhibitors, is an option for patients who do not meet the criteria for chemotherapy or sole endocrine treatment. The first AI introduced in 1999 was AROMASIN (Exemestane), which proved effective as a second-line therapy for postmenopausal women with HR-positive MBC following tamoxifen treatment.
The addition of the three registered CDK4/6 inhibitors (CDK4/6i) to an endocrine drug in the first line of treatment, like in MONALEESA 2, 3, and 7 (ribociclib), PALOMA-2 (palbociclib) and MONARCH-3 (abemaciclib) showed a significant increase in the median progression-free survival (PFS).
There is promising potential for expanding CDK4/6 inhibitor applications beyond HR+, HER2- advanced breast cancer. Patients who develop resistance to combined CDK4/6 inhibitor and endocrine treatments often switch to conventional chemotherapy due to disappointing outcomes with single-agent fulvestrant. Recent developments suggest that the post-CDK4/6 inhibitor treatment landscape could benefit from adopting Antibody-Drug Conjugates (ADCs) and oral selective estrogen receptor degraders (SERDs).
The emerging pipeline is crowded by HR+/HER2- potential therapies whereas few of them have shifted their focus to evaluate the therapies targeting HER2 Low segment. The emerging pipeline for HR/HER2- includes several potential drugs in late-stage (Phase III, II/III, II) that include Giredestrant, Camizestrant (AZD9833), LY3484356 (Imlunestrant), Lasofoxifene, ARV-471, Capivasertib, Inavolisib, KEYTRUDA (pembrolizumab), Enobosarm, OP1250, Samuraciclib, Lerociclib, SFX-01, Endoxifen, whereas HER2 Low include Datopotamab deruxtecan, DB1303, Eftilagimod alpha, being administered in various combinations. The focus of this research is mostly on new oral SERDs.
Detailed market assessment will be provided in the final report.
This section focuses on the uptake rate of potential drugs expected to be launched in the market during 2019-2032. The landscape of HR+/HER2- breast cancer treatment has experienced a profound transformation with the uptake of novel drugs. These innovative therapies are redefining standards of care. Furthermore, the increased uptake of these transformative drugs is a testament to the unwavering dedication of physicians, oncology professionals, and the entire healthcare community in their tireless pursuit of advancing cancer care. This momentous shift in treatment paradigms is a testament to the power of research, collaboration, and human resilience.
Detailed emerging therapies assessment will be provided in the final report.
The report provides insights into therapeutic candidates in Phase III and Phase II stages. It also analyzes key players involved in developing targeted therapeutics.
The report covers information on collaborations, acquisitions and mergers, licensing, and patent details for HR+/HER2- breast cancer emerging therapy.
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 the HR+/HER2- breast cancer evolving treatment landscape, patient reliance on conventional therapies, patient therapy switching acceptability, and drug uptake, along with challenges related to accessibility, including oncologists, radiation oncologists, surgical oncologists, and others.
DelveInsight's analysts connected with 30+ KOLs to gather insights; however, interviews were conducted with 15+ KOLs in the 7MM. Centers such as Institute for Personalized Cancer Therapy, Anderson Cancer Center, Aichi Cancer Center, University Hospital Ulm, International Breast Cancer Center, etc., were contacted. Their opinion helps understand and validate current and emerging therapy treatment patterns or HR+/HER2- 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.
We perform 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 Patient Assistance Now Oncology (PANO) program assists with accessing Novartis medicine(s), from insurance verification to financial assistance. Free Trial and Access Program can help patients receive a free PIQRAY supply for a US FDA-approved indication. Patients may be eligible for immediate copay savings with a PIQRAY copay card; eligible patients with private insurance may pay USD 0 per month, and Novartis will pay the remaining copay, up to USD 15,000 per calendar year, per product. The program is unavailable for patients enrolled in Medicare, Medicaid, or any other federal or state healthcare program.
Novartis supports the patients in accessing AFINITOR through its Oncology Universal Copay Program, through which eligible patients with private insurance may pay USD 0 per month, and Novartis will pay the remaining copay, up to USD 15,000 per calendar year per product. AfiniTRAC is another support program for eligible patients taking AFINITOR (everolimus) tablets or AFINITOR DISPERZ (everolimus tablets for oral suspension). The program provides one-to-one telephone support directly to patients through AfiniTRAC Care Champions, who provide comprehensive educational support, including help with a treatment routine and reminders to patients to take medication as prescribed.
Detailed market access and reimbursement assessment will be provided in the final report.