Letrozole
- Generic Name
- Letrozole
- Brand Names
- Femara, Kisqali Femara Co-pack
- Drug Type
- Small Molecule
- Chemical Formula
- C17H11N5
- CAS Number
- 112809-51-5
- Unique Ingredient Identifier
- 7LKK855W8I
- Background
Letrozole, or CGS 20267, is an oral non-steroidal type II aromatase inhibitor first described in the literature in 1990. It is a third generation aromatase inhibitor like exemestane and anastrozole, meaning it does not significantly affect cortisol, aldosterone, and thyroxine.
Letrozole was granted FDA approval on 25 July 1997.
- Indication
Letrozole is indicated to treat postmenopausal women with hormone receptor (HR) positive early breast cancer, postmenopausal women with early breast cancer who have periviously been treated with tamoxifen, and postmenopausal women with HR+ or unknown advanced breast cancer. Letrozole, given with ribociclib, is indicated to treat pre, peri, and postmenopausal women with HR+ and human epidermal growth factor 2 (HER2) negative advanced or metastatic breast cancer.
- Associated Conditions
- Advanced Breast Cancer, Anovulatory cycle, Epithelial Ovarian Cancer, HR+, HER2-, Advanced Breast Cancer, Stage I Breast Cancer, Metastatic HR + HER2 - breast cancer
Ribociclib-Letrozole Combo Shows Promising 24% Response Rate in Low-Grade Serous Ovarian Cancer Trial
• Phase 2 GOG 3026 trial demonstrates ribociclib plus letrozole achieves 24% response rate in low-grade serous ovarian cancer, surpassing current treatment options' efficacy.
• The combination therapy shows favorable tolerability profile, building on established safety protocols from breast cancer treatment experience.
• Researchers anticipate inclusion in NCCN guidelines, though optimal treatment timing and sequencing remain under investigation for future clinical trials.
Lerociclib Plus Fulvestrant Shows Promise in HR+/HER2- Advanced Breast Cancer
• The LEONARDA-1 phase 3 trial demonstrated that lerociclib plus fulvestrant significantly improved progression-free survival (PFS) compared to placebo plus fulvestrant in patients with HR+/HER2- advanced breast cancer.
• The combination of lerociclib and fulvestrant showed a manageable safety profile, with hematological toxicities being the most common adverse events, effectively managed with dose adjustments.
• Lerociclib plus fulvestrant exhibited efficacy across various patient subgroups, including those with primary endocrine therapy resistance and liver metastasis, addressing a critical unmet need.
• The study supports lerociclib plus fulvestrant as a potential treatment option for patients with HR+/HER2- advanced breast cancer who have progressed on prior endocrine therapy.
Bayer's Elinzanetant Shows Promise in Reducing Hot Flashes for Breast Cancer Patients
• Elinzanetant met primary endpoints in the Phase III OASIS 4 trial, significantly reducing the frequency of moderate to severe vasomotor symptoms (VMS) in women undergoing endocrine therapy for breast cancer.
• The study also achieved secondary endpoints, demonstrating a reduction in the severity of VMS, improvements in sleep disturbances, and enhanced menopause-related quality of life compared to placebo.
• Elinzanetant is a dual neurokinin-1 and 3 receptor antagonist, representing a potential non-hormonal treatment option for VMS in breast cancer patients and women at high risk.
• Bayer is advancing regulatory submissions for elinzanetant in the US, EU, and other global markets, with potential launch expected later this year, pending regulatory approvals.
FDA Approvals in 2024: Advancing Treatment Paradigms in Solid Tumors and Hematologic Malignancies
• The FDA granted over 65 approvals in 2024, significantly impacting treatment paradigms across various cancers, including breast, gynecologic, skin, and genitourinary malignancies.
• Several tumor-agnostic approvals, such as fam-trastuzumab deruxtecan-nxki (Enhertu) for HER2-positive solid tumors and repotrectinib (Augtyro) for NTRK fusion-positive tumors, marked advancements in precision medicine.
• Immunotherapies like nivolumab (Opdivo) and pembrolizumab (Keytruda) received multiple approvals, including combinations with chemotherapy for urothelial and endometrial carcinomas, improving patient outcomes.
• Targeted therapies like vorasidenib (Voranigo) for low-grade glioma and selpercatinib (Retevmo) for RET-mutated thyroid cancers addressed unmet needs and demonstrated high efficacy and tolerability.
Ribociclib Plus Endocrine Therapy Shows Promise in Specific Breast Cancer Subtypes
• A subgroup analysis of the RIGHT Choice study suggests ribociclib plus endocrine therapy may offer a progression-free survival (PFS) benefit in luminal B/HER2E breast cancer subtypes.
• Patients with low baseline expression of immune-related genes experienced a longer median PFS when treated with ribociclib and endocrine therapy compared to chemotherapy.
• In luminal B/HER2E subtypes, ribociclib plus endocrine therapy showed a median PFS of 38.0 months versus 18.4 months with combination chemotherapy.
• The study indicates potential predictive value of immune-related gene signatures, warranting further investigation despite small sample sizes.
Advancements in Breast Cancer Research Unveiled at SABCS 2024
• The PATINA trial suggests palbociclib with anti-HER2 and endocrine therapy may become a new standard for HR+, HER2+ metastatic breast cancer.
• COMET trial indicates active monitoring is comparable to surgery for low-risk DCIS, offering a potential alternative management option.
• OlympiA trial's long-term results reinforce olaparib's role in preventing recurrence and highlight the importance of BRCA testing for early-stage breast cancer.
Camrelizumab and Apatinib Show Promise in Neoadjuvant Treatment of TNBC
• Camrelizumab plus chemotherapy significantly improved pathologic complete response (pCR) rates in early or locally advanced triple-negative breast cancer (TNBC).
• Apatinib combined with sintilimab and chemotherapy demonstrated a high pCR rate of 70.6% in early TNBC, suggesting synergistic effects.
• Both camrelizumab and apatinib regimens exhibited manageable safety profiles, supporting their potential as new neoadjuvant therapeutic options.
• Biomarker analysis in the apatinib study identified correlations between immune response and pCR, offering insights for predicting treatment efficacy.
Patritumab Deruxtecan Shows Efficacy in High-Risk HR+/HER2- Breast Cancer
• Patritumab deruxtecan, with or without letrozole, shows comparable efficacy to multiagent chemotherapy in high-risk, HR+/HER2- breast cancer patients.
• The phase 2 SOLTI VALENTINE trial demonstrated similar pathologic complete response (pCR) and objective response rate (ORR) with the antibody-drug conjugate.
• Treatment with patritumab deruxtecan resulted in fewer grade 3 or higher treatment-related adverse events compared to standard chemotherapy.
• The study supports the potential incorporation of patritumab deruxtecan in treating high-risk HR-positive/HER2-negative early breast cancer.
Novartis' Kisqali Receives EC Approval for Early Breast Cancer Treatment
• The European Commission (EC) has approved Novartis' Kisqali (ribociclib) in combination with an aromatase inhibitor for adjuvant treatment of HR+/HER2- early breast cancer.
• The approval is based on the Phase III NATALEE trial, demonstrating a 25.1% reduction in the risk of disease recurrence compared to endocrine therapy alone.
• Kisqali is now approved for a broader population of early breast cancer patients in Europe, including those with node-negative disease at high risk of recurrence.
• The decision follows positive recommendations and aligns with recent FDA approvals and NCCN guidelines, reinforcing Kisqali's role in early breast cancer treatment.
Kisqali and Itovebi Secure FDA Approval for Advanced Breast Cancer Treatment
• Ribociclib (Kisqali) gains FDA approval in combination with aromatase inhibitors for adjuvant treatment of HR+/HER2- early breast cancer, reducing recurrence risk.
• Inavolisib (Itovebi) receives FDA approval when combined with palbociclib and fulvestrant for endocrine-resistant, PIK3CA-mutated, HR-positive, HER2-negative advanced breast cancer.
• The approvals offer new treatment options for a broader range of breast cancer patients, addressing unmet needs and improving care approaches.
Ribociclib Shows Promise in Advanced Breast Cancer Treatment
• Ribociclib, a CDK 4/6 inhibitor by Novartis, significantly improved progression-free survival when combined with letrozole in patients with hormone receptor-positive advanced breast cancer.
• The MONALEESA-2 trial demonstrated a 63.0% progression-free survival rate at 18 months for ribociclib plus letrozole, compared to 42.2% with letrozole alone.
• Common side effects of ribociclib include neutropenia, infection, hair loss, diarrhea, and nausea, with a small percentage of patients experiencing a prolonged QT interval.
• Ribociclib's efficacy and potential high cost raise questions about its accessibility and how it compares to similar drugs like palbociclib.
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