CLINICAL TRIALS PROFILE FOR LETROZOLE

505(b)(2) Clinical Trials for letrozole

This table shows clinical trials for potential 505(b)(2) applications. See the next table for all clinical trials

Trial Type	Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
New Indication	NCT01175096 ↗	Safety and Tolerability Profile of RAD001 Daily in Chinese Patients With Advanced Pulmonary Neuroendocrine Tumor	Unknown status	Novartis	Phase 1/Phase 2	2010-07-01	RAD001 continues to be investigated as an anticancer agent on new indications such as neuroendocrine tumors (incl. carcinoid), breast cancer, liver cancer, gastric cancer and lymphoma based on its potential to act: - directly on the tumor cells by inhibiting tumor cell growth and proliferation - indirectly by inhibiting angiogenesis leading to reduced tumor vascularity (via potent inhibition of tumor cell HIF-1 activity and VEGF production and VEGF-induced proliferation of endothelial cells) A role for RAD001 in combination with Sandostatin LAR® Depot in the treatment of advanced carcinoid tumor is suggested by data on the regulatory role of mTOR in cell growth and protein translation and the finding that somatostatin-induced growth arrest is mediated in part by inhibition of the PI3K pathway (Charland, et al. 2001). The present study is designed to collect safety/tolerability data and evidences for efficacy of RAD001 in the medically highly unmet indication of advanced pulmonary neuroendocrine tumor in Chinese patients.
New Indication	NCT01175096 ↗	Safety and Tolerability Profile of RAD001 Daily in Chinese Patients With Advanced Pulmonary Neuroendocrine Tumor	Unknown status	Guangdong General Hospital	Phase 1/Phase 2	2010-07-01	RAD001 continues to be investigated as an anticancer agent on new indications such as neuroendocrine tumors (incl. carcinoid), breast cancer, liver cancer, gastric cancer and lymphoma based on its potential to act: - directly on the tumor cells by inhibiting tumor cell growth and proliferation - indirectly by inhibiting angiogenesis leading to reduced tumor vascularity (via potent inhibition of tumor cell HIF-1 activity and VEGF production and VEGF-induced proliferation of endothelial cells) A role for RAD001 in combination with Sandostatin LAR® Depot in the treatment of advanced carcinoid tumor is suggested by data on the regulatory role of mTOR in cell growth and protein translation and the finding that somatostatin-induced growth arrest is mediated in part by inhibition of the PI3K pathway (Charland, et al. 2001). The present study is designed to collect safety/tolerability data and evidences for efficacy of RAD001 in the medically highly unmet indication of advanced pulmonary neuroendocrine tumor in Chinese patients.
New Indication	NCT01175096 ↗	Safety and Tolerability Profile of RAD001 Daily in Chinese Patients With Advanced Pulmonary Neuroendocrine Tumor	Unknown status	Guangdong Provincial People's Hospital	Phase 1/Phase 2	2010-07-01	RAD001 continues to be investigated as an anticancer agent on new indications such as neuroendocrine tumors (incl. carcinoid), breast cancer, liver cancer, gastric cancer and lymphoma based on its potential to act: - directly on the tumor cells by inhibiting tumor cell growth and proliferation - indirectly by inhibiting angiogenesis leading to reduced tumor vascularity (via potent inhibition of tumor cell HIF-1 activity and VEGF production and VEGF-induced proliferation of endothelial cells) A role for RAD001 in combination with Sandostatin LAR® Depot in the treatment of advanced carcinoid tumor is suggested by data on the regulatory role of mTOR in cell growth and protein translation and the finding that somatostatin-induced growth arrest is mediated in part by inhibition of the PI3K pathway (Charland, et al. 2001). The present study is designed to collect safety/tolerability data and evidences for efficacy of RAD001 in the medically highly unmet indication of advanced pulmonary neuroendocrine tumor in Chinese patients.
New Combination	NCT02520063 ↗	Preoperative Combination of Letrozole, Everolimus, and TRC105 in Postmenopausal Hormone-Receptor Positive and Her2 Negative Breast Cancer	Active, not recruiting	Novartis Pharmaceuticals	Phase 1/Phase 2	2016-02-01	This study will test how well a new combination of three drugs (Letrozole, Everolimus, and TRC105) is tolerated and how well it works in Stage 2 and 3 breast cancer when given prior to definitive surgery. Letrozole blocks the estrogen receptor expressed by many breast cancers while everolimus blocks signals that drive cancer cells to grow. TRC105 is an investigational drug that blocks the formation and growth of blood vessels that feed the cancer and promote its growth. The goal of this study is to investigate the safety and efficacy of this multitargeted approach in breast cancer.
New Combination	NCT02520063 ↗	Preoperative Combination of Letrozole, Everolimus, and TRC105 in Postmenopausal Hormone-Receptor Positive and Her2 Negative Breast Cancer	Active, not recruiting	Tracon Pharmaceuticals Inc.	Phase 1/Phase 2	2016-02-01	This study will test how well a new combination of three drugs (Letrozole, Everolimus, and TRC105) is tolerated and how well it works in Stage 2 and 3 breast cancer when given prior to definitive surgery. Letrozole blocks the estrogen receptor expressed by many breast cancers while everolimus blocks signals that drive cancer cells to grow. TRC105 is an investigational drug that blocks the formation and growth of blood vessels that feed the cancer and promote its growth. The goal of this study is to investigate the safety and efficacy of this multitargeted approach in breast cancer.
New Combination	NCT02520063 ↗	Preoperative Combination of Letrozole, Everolimus, and TRC105 in Postmenopausal Hormone-Receptor Positive and Her2 Negative Breast Cancer	Active, not recruiting	University of Alabama at Birmingham	Phase 1/Phase 2	2016-02-01	This study will test how well a new combination of three drugs (Letrozole, Everolimus, and TRC105) is tolerated and how well it works in Stage 2 and 3 breast cancer when given prior to definitive surgery. Letrozole blocks the estrogen receptor expressed by many breast cancers while everolimus blocks signals that drive cancer cells to grow. TRC105 is an investigational drug that blocks the formation and growth of blood vessels that feed the cancer and promote its growth. The goal of this study is to investigate the safety and efficacy of this multitargeted approach in breast cancer.

All Clinical Trials for letrozole

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT00001521 ↗	Three Drug Combination Therapy Versus Conventional Treatment of Children With Congenital Adrenal Hyperplasia	Active, not recruiting	Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)	Phase 2	1995-06-08	This study was developed to determine if a combination of four drugs (flutamide, testolactone, reduced hydrocortisone dose, and fludrocortisone) can normalize growth in children with congenital adrenal hyperplasia. The study will take 60 children, boys and girls and divide them into 2 groups based on the medications given. Group one will receive the new four- drug combination. Group two will receive the standard treatment for congenital adrenal hyperplasia (hydrocortisone and fludrocortisone). The boys in group one will take the medication until the age of 14 at which time they will stop taking the four drug combination and begin receiving the standard treatment for congenital adrenal hyperplasia. Girls in group one will take the four drug combination until the age of 13, at which time they will stop and begin receiving the standard treatment for congenital adrenal hyperplasia plus flutamide. Flutamide will be given to the girls until six months after their first menstrual period. All of the children will be followed until they reach their final adult height. The effectiveness of the treatment will be determined by measuring the patient's adult height, body mass index, and bone density. ...
NCT00003140 ↗	Letrozole After Tamoxifen in Treating Women With Breast Cancer	Completed	Cancer and Leukemia Group B	Phase 3	1998-08-24	RATIONALE: Estrogen can stimulate the growth of breast cancer cells. Hormone therapy using letrozole may fight breast cancer by reducing the production of estrogen. PURPOSE: This randomized phase III trial is studying letrozole to see how well it works in treating women with breast cancer who have received tamoxifen for at least 5 years.
NCT00003140 ↗	Letrozole After Tamoxifen in Treating Women With Breast Cancer	Completed	Eastern Cooperative Oncology Group	Phase 3	1998-08-24	RATIONALE: Estrogen can stimulate the growth of breast cancer cells. Hormone therapy using letrozole may fight breast cancer by reducing the production of estrogen. PURPOSE: This randomized phase III trial is studying letrozole to see how well it works in treating women with breast cancer who have received tamoxifen for at least 5 years.
NCT00003140 ↗	Letrozole After Tamoxifen in Treating Women With Breast Cancer	Completed	European Organisation for Research and Treatment of Cancer - EORTC	Phase 3	1998-08-24	RATIONALE: Estrogen can stimulate the growth of breast cancer cells. Hormone therapy using letrozole may fight breast cancer by reducing the production of estrogen. PURPOSE: This randomized phase III trial is studying letrozole to see how well it works in treating women with breast cancer who have received tamoxifen for at least 5 years.
NCT00003140 ↗	Letrozole After Tamoxifen in Treating Women With Breast Cancer	Completed	International Breast Cancer Study Group	Phase 3	1998-08-24	RATIONALE: Estrogen can stimulate the growth of breast cancer cells. Hormone therapy using letrozole may fight breast cancer by reducing the production of estrogen. PURPOSE: This randomized phase III trial is studying letrozole to see how well it works in treating women with breast cancer who have received tamoxifen for at least 5 years.
NCT00003140 ↗	Letrozole After Tamoxifen in Treating Women With Breast Cancer	Completed	National Cancer Institute (NCI)	Phase 3	1998-08-24	RATIONALE: Estrogen can stimulate the growth of breast cancer cells. Hormone therapy using letrozole may fight breast cancer by reducing the production of estrogen. PURPOSE: This randomized phase III trial is studying letrozole to see how well it works in treating women with breast cancer who have received tamoxifen for at least 5 years.

Clinical Trial Conditions for letrozole

Condition Name

Condition Name for letrozole
Intervention	Trials
Breast Cancer	232
Metastatic Breast Cancer	43
Infertility	36
Breast Neoplasms	33

Condition MeSH

Condition MeSH for letrozole
Intervention	Trials
Breast Neoplasms	410
Infertility	55
Polycystic Ovary Syndrome	52
Carcinoma	28

Clinical Trial Locations for letrozole

Trials by Country

Trials by Country for letrozole
Location	Trials
Italy	371
Spain	265
China	245
Canada	175
Japan	143

Trials by US State

Trials by US State for letrozole
Location	Trials
California	102
Texas	101
Florida	80
New York	75
Massachusetts	75

Clinical Trial Progress for letrozole

Clinical Trial Phase

Clinical Trial Phase for letrozole
Clinical Trial Phase	Trials
PHASE4	3
PHASE3	19
PHASE2	21

Clinical Trial Status

Clinical Trial Status for letrozole
Clinical Trial Phase	Trials
Completed	222
Recruiting	157
Active, not recruiting	78

Clinical Trial Sponsors for letrozole

Sponsor Name

Sponsor Name for letrozole
Sponsor	Trials
Novartis Pharmaceuticals	61
National Cancer Institute (NCI)	61
Pfizer	42

Sponsor Type

Sponsor Type for letrozole
Sponsor	Trials
Other	729
Industry	320
NIH	74

Clinical Trials Update, Market Analysis, and Projection for Letrozole

Last updated: October 11, 2025

Introduction

Letrozole, an aromatase inhibitor, is primarily prescribed for hormone receptor-positive breast cancer in postmenopausal women. Approved by the FDA in 1999, it plays a vital role in adjuvant therapy and management of metastatic breast cancer. As the oncology landscape evolves, continuous clinical investigations and market dynamics influence its adoption and future growth prospects. This report provides a comprehensive update on clinical trials involving letrozole, an in-depth market analysis, and projections over the next decade.

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Clinical Trials Update

Ongoing and Recent Clinical Trials

Letrozole remains a focal point in breast cancer treatment research. According to ClinicalTrials.gov, as of 2023, over 50 active and completed trials investigate its various applications, including combination therapies, extended adjuvant therapy, and novel indications.

• Extended Adjuvant Therapy: Multiple studies evaluate the efficacy of longer-term letrozole administration. For instance, the MA.17R trial (NCT00432363) assessed the benefits of five additional years of letrozole for early-stage hormone receptor-positive breast cancer. Results demonstrated significant improvements in disease-free survival (DFS), prompting guidelines to consider extended therapy for select patient populations.

• Combination Therapies: Trials like NCT02670158 explore letrozole combined with CDK4/6 inhibitors such as palbociclib. These studies aim to enhance treatment efficacy in advanced breast cancer cases. Preliminary data suggest synergistic effects, reduced recurrence, and delayed disease progression.

• Prevention and Risk Reduction: The IBIS-II Prevention Trial (NCT00084145) investigates letrozole's role in breast cancer prevention among high-risk postmenopausal women, confirming its potential in chemoprevention strategies.

• Innovative Indications: Emerging studies are exploring letrozole's off-label applications, such as ovarian stimulation and endometriosis management, although these are in preliminary phases.

Regulatory Endorsements and Data

Recent updates from the American Society of Clinical Oncology (ASCO) and European Society for Medical Oncology (ESMO) reaffirm letrozole's standing as a standard of care in hormone receptor-positive breast cancer. The ADAURA trial results published in 2022 showed that combining letrozole with targeted therapy prolongs DFS in invasive disease scenarios. These findings underpin current guideline recommendations.

Safety and Resistance Concerns

Ongoing trials focus on addressing resistance mechanisms associated with long-term letrozole therapy. Biomarker-driven studies identify patients more likely to benefit from alternative strategies, including combination with mTOR inhibitors. The emergence of resistance remains a clinical challenge, inspiring research into next-generation aromatase inhibitors and personalized approaches.

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Market Analysis

Current Market Landscape

The global letrozole market was valued at approximately USD 1.4 billion in 2022 and is projected to reach USD 2.2 billion by 2030, growing at a compounded annual growth rate (CAGR) of around 6%.[1] This outlook reflects increasing incidence rates of breast cancer, evolving clinical guidelines favoring aromatase inhibitors, and expanding indications.

Key Market Players

Major pharmaceutical companies engaged in the letrozole segment include:

• Novartis AG: The original manufacturer, with branded product Femara®, dominates the market. Novartis continues to invest in clinical trials to expand its therapeutic indications.
• Teva Pharmaceuticals: Offers generic formulations, catering to cost-sensitive markets and driving broader access.
• Mylan and Sandoz: Other significant players creating generic alternatives, intensifying competition.

Regional Market Dynamics

• North America: The largest market, supported by high breast cancer awareness, advanced healthcare infrastructure, and favorable reimbursement policies. The United States accounts for nearly 40% of global sales.
• Europe: Steady growth, driven by aging populations and adoption of guideline-directed therapies.
• Asia-Pacific: Fastest-growing segment, with increasing breast cancer prevalence, improving healthcare access, and rising awareness. Countries like China and India are expanding the use of generics and affordable options.
• Latin America and Middle East/Africa: Emerging markets with expanding oncology infrastructure and increasing disease burden.

Market Drivers

• Rising breast cancer diagnostics and screening programs.
• Adoption of aromatase inhibitors as first-line therapy over selective estrogen receptor modulators (SERMs) like tamoxifen.
• Expanded use in extended adjuvant therapy and metastatic settings.
• Growing acceptance of combination therapy with targeted agents.

Market Restraints

• Patent expiry and proliferation of generic versions reducing revenue.
• Side effect profile leading to therapy discontinuations (e.g., osteoporosis, arthralgia).
• Resistance mechanisms necessitating alternative treatment options.

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Market Projections and Future Outlook

Growth Drivers

• Increased Incidence: Breast cancer remains the most diagnosed cancer among women globally, with an anticipated increase of 40% by 2040.[2] This trend sustains demand for effective hormonal therapies like letrozole.
• Guideline Advancements: Evolving clinical guidelines increasingly favor aromatase inhibitors, including extended adjuvant applications, thereby broadening market scope.
• Research and Development: Ongoing trials exploring combination therapies and chemopreventive roles may introduce novel, expanded indications.

Key Opportunities

• Personalized Medicine: Biomarker-driven treatment selection can optimize therapy, improve outcomes, and expand the patient population eligible for letrozole.
• Generic Market Expansion: Cost reduction and accessibility improvements in emerging markets will fuel volume growth.
• New Formulations: Development of sustained-release or combination formulations could enhance adherence and therapeutic outcomes.

Market Challenges

• Patent Expiries: The expiration of patents in the coming years will intensify competition from generics, impacting revenue.
• Side Effect Management: Addressing adverse effects remains crucial for maintaining adherence and expanding long-term use.
• Emerging Therapies: Competition from novel agents like CDK4/6 inhibitors, mTOR inhibitors, and selective estrogen receptor degraders (SERDs) could shift treatment paradigms away from solely aromatase inhibitors.

Forecast Summary

By 2030, the global letrozole market is expected to grow at a CAGR of approximately 5.5–6%, driven by increased breast cancer prevalence, guideline changes favoring aromatase inhibitors, and expanded indications. Despite challenges from patent expiries and emerging therapies, strategic positioning through pipeline expansion, combination regimens, and personalized treatment approaches will be essential for sustained growth.

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Key Takeaways

• Clinical landscape shows ongoing, promising trials that support letrozole's extended use, combination therapies, and preventive applications, reinforcing its core role in breast cancer management.
• Market growth is driven by rising breast cancer incidence, evolving treatment guidelines, and expanding therapy indications, especially in Asia-Pacific and emerging markets.
• Patent expiries and generic competition threaten revenue streams; however, opportunities in combination therapies and personalized medicine could mitigate this.
• Research priorities include overcoming resistance mechanisms and optimizing long-term safety profiles to improve adherence.
• Strategic focus for stakeholders should involve diversification of indications, development of novel formulations, and expansion into underserved markets.

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FAQs

1. What is the primary therapeutic use of letrozole?
Letrozole is primarily used as an adjuvant treatment for hormone receptor-positive early-stage breast cancer in postmenopausal women and for metastatic disease. It works by inhibiting aromatase, reducing estrogen production.

2. How does ongoing research impact the future of letrozole?
Current clinical trials exploring combination therapies, extended adjuvant use, and chemopreventive roles suggest potential expanded indications and improved treatment outcomes, which could bolster its market position and clinical relevance.

3. What are the main challenges facing the letrozole market?
Patent expiries leading to generic competition, side effects limiting adherence, and emerging treatments like CDK4/6 inhibitors pose challenges to sustained growth.

4. How is the global market for letrozole expected to evolve?
The market is projected to grow steadily with a CAGR of about 6%, driven mainly by increasing breast cancer cases, expanding indications, and geographic growth in emerging markets.

5. What opportunities exist for pharmaceutical companies regarding letrozole?
Opportunities include developing combination regimens, expanding indications into chemoprevention, creating novel formulations to improve compliance, and entering underserved markets through cost-effective Generic options.

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References

[1] MarketWatch, “Letrozole Market Size, Share & Trends Analysis Report,” 2022.
[2] World Health Organization, “Breast Cancer Fact Sheet,” 2021.