Letrozole, Leuprorelin, and Ribociclib combination

The combination of letrozole, leuprorelin, and ribociclib is a therapeutic regimen used primarily in hormone receptor-positive (HR+), HER2-negative advanced or metastatic breast cancer. This combination therapy represents a targeted approach that combines endocrine therapy with a CDK4/6 inhibitor. ## Mechanism of Action This combination works through complementary mechanisms: - **Ribociclib** is a CDK4/6 inhibitor that decreases retinoblastoma (Rb) protein phosphorylation, leading to G1 phase cell cycle arrest and decreased cell proliferation in breast cancer cell lines[1][3]. - **Letrozole** is an aromatase inhibitor that works by decreasing the amounts of estrogen in the body, which can stimulate the growth of hormone receptor-positive breast cancers[3]. - **Leuprorelin** (also known as leuprolide) is a gonadotropin-releasing hormone (GnRH) agonist that suppresses estrogen production in premenopausal women and men, making the letrozole therapy effective in these populations[2][4]. ## Clinical Use This combination is specifically used for: - Pre/perimenopausal women with HR+/HER2- advanced breast cancer (with leuprorelin or goserelin as the GnRH agonist)[4][6] - Men with HR+/HER2- advanced breast cancer (with leuprorelin or goserelin)[1][2] - Postmenopausal women with HR+/HER2- advanced breast cancer (without the need for leuprorelin)[3][6] ## Dosing Regimen The standard dosing regimen includes: - Ribociclib: 600 mg orally daily for 3 weeks on, 1 week off (21/7 schedule) in a 28-day cycle[2][4][6] - Letrozole: 2.5 mg orally daily continuously through the 28-day cycle[2][4][6] - Leuprorelin (for men and premenopausal women): 7.5 mg as an intramuscular depot injection once every 28 days[4] - Alternatively, goserelin 3.6 mg subcutaneous implant can be used[2][4] ## Safety Profile The most common adverse effects include: - Neutropenia (most common grade ≥3 adverse effect)[2][4] - Leukopenia[2][6] - Nausea and vomiting[2][6] - Fatigue[6] - Transaminase elevations[4] - Diarrhea[6] In clinical studies, dose adjustments or interruptions were common (63.1% in one study), but discontinuation due to adverse events was relatively low (10.6%)[4]. ## Clinical Evidence The efficacy of this combination has been demonstrated in several clinical trials: - The CompLEEment-1 trial included men and women of any menopausal status with HR+/HER2- advanced breast cancer and showed favorable safety and efficacy results[2][4] - For male patients, the FDA approval was based on previous favorable benefit-risk assessments from MONALEESA-2 and MONALEESA-7 trials, supported by the COMPLEEMENT-1 trial[1] - The combination has shown efficacy in patients with CNS metastases, with an overall response rate of 42.9% and a clinical benefit rate of 62.9%[2] This combination represents an important treatment option for HR+/HER2- advanced breast cancer across different patient populations, including those traditionally excluded from clinical trials.

Other names

Letrozole, Leuprorelin, and Ribociclib combination therapy