Ribociclib 200mg tablets

AimsThis study aimed to evaluate the comprehensive safety profile of CDK4/6 inhibitors in breast cancer treatment by analyzing real-world adverse event (AE) data and systematically reviewing clinical trial findings to provide evidence-based safety guidance.MethodsA disproportionality analysis based on real-world data from the FDA adverse event reporting system (FAERS) was combined with a systematic review to evaluate adverse events (AEs) associated with CDK4/6 inhibitors. A total of 16 studies involving 6,722 patients with advanced breast cancer were included to analyze the toxicity risks of CDK4/6 inhibitor combination therapies. Temporal patterns of AEs were assessed using FAERS data, and signal strengths were determined using the reporting odds ratio (ROR).ResultsCombination therapy with CDK4/6 inhibitors significantly increased the risk of grade 3-5 AEs. FAERS analysis revealed that most AEs occurred within the first month of treatment, with the lowest incidence between the second and sixth months, followed by a significant rise thereafter. All CDK4/6 inhibitors were associated with myelosuppression, gastrointestinal toxicity, interstitial lung disease (ILD), and QT prolongation. Disproportionality analysis for "Torsade de pointes/QT prolongation" identified Ribociclib as the only agent with a strong positive signal (ROR 6.16, 95% CI 5.54-6.84). Additionally, unexpected AEs such as peripheral neuropathy, taste disorders, and epistaxis were detected.ConclusionClinicians should prioritize monitoring for myelosuppression, gastrointestinal toxicity, and QT prolongation (particularly with Ribociclib) during the first month of CDK4/6 inhibitor therapy. Long-term surveillance beyond 6 months is crucial to detect delayed-onset AEs.

Abstract licence: CC BY

Determine the efficacy and safety of first-line ribociclib plus letrozole in elderly patients with HR+, HER2- advanced breast cancer. 668 postmenopausal women with HR+, HER2- advanced breast cancer and no prior systemic therapy for advanced disease were enrolled in the Phase III MONALEESA-2 trial (NCT01958021); 295 patients were aged ≥ 65 years. Patients were randomized to ribociclib (600 mg/day; 3-weeks-on/1-week-off) plus letrozole (2.5 mg/day) or placebo plus letrozole until disease progression, unacceptable toxicity, death, or treatment discontinuation. The primary endpoint was PFS, which was evaluated in elderly (≥ 65 years) and younger ( Ribociclib plus letrozole significantly improved PFS vs placebo plus letrozole in elderly (hazard ratio: 0.608; 95% CI 0.394-0.937) and younger patients (hazard ratio: 0.523; 95% CI 0.378-0.723). Overall response rates were numerically higher in the ribociclib vs placebo arm, regardless of age. Ribociclib plus letrozole was well tolerated in elderly patients, with the safety profile similar to the overall study population. Nausea, vomiting, alopecia, and diarrhea were > 10% more frequent in the ribociclib plus letrozole vs placebo plus letrozole arm in both subgroups; most events were grade 1/2. In elderly patients, grade 1/2 anemia and fatigue were > 10% more frequent in the ribociclib plus letrozole vs placebo plus letrozole arm and discontinuation rates were similar in both arms. Addition of ribociclib to letrozole is a valid therapeutic option for elderly patients with HR+, HER2- advanced breast cancer in the first-line setting

Abstract licence: CC BY 4.0