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Severe diarrhea associated with dehydration and infection has been reported in patients receiving abemaciclib. Across four clinical trials involving 3,691 patients, the incidence of diarrhea in abemaciclib-treated patients ranged from 81% to 90%. Among these, grade 3 diarrhea occurred in 8% to 20% of abemaciclib-treated patients. Most patients developed diarrhea within the first month of abemaciclib treatment. The median time to first diarrhea event was 6 to 8 days; the median duration of grade 2 and grade 3 diarrhea was 6 to 11 days and 5 to 8 days, respectively. In all trials, 19% to 26% of patients with diarrhea required abemaciclib dose interruption, and 13% to 23% required dose reduction.
Patients should be instructed to initiate antidiarrheal therapy (e.g., loperamide) at the first sign of loose stools, increase oral fluid intake, and notify their healthcare provider for further guidance and appropriate follow-up. For grade 3 or 4 diarrhea, or diarrhea requiring hospitalization, discontinue abemaciclib until toxicity resolves to ≤ grade 1, then resume abemaciclib at the next lower dose.
Neutropenia, including febrile neutropenia and fatal neutropenic sepsis, has been reported in patients receiving abemaciclib. Across four clinical trials involving 3,691 patients, the incidence of neutropenia in abemaciclib-treated patients ranged from 37% to 46%. Among these, 19% to 32% of abemaciclib-treated patients experienced ≥ grade 3 neutropenia (based on laboratory findings). In all trials, the median time to first occurrence of ≥ grade 3 neutropenia was 29 to 33 days, and the median duration of ≥ grade 3 neutropenia was 11 to 16 days. The reported incidence of febrile neutropenia was < 1% in abemaciclib-treated patients across all trials. Two deaths due to neutropenic sepsis were observed in the MONARCH2 trial.
Patients should be advised to immediately notify their healthcare provider if any fever develops. Monitor complete blood counts (CBC) prior to initiating abemaciclib, every 2 weeks for the first 2 months of treatment, monthly for the next 2 months, and as clinically indicated. For patients with grade 3 or 4 neutropenia, dose interruption, dose reduction, or delay in starting treatment cycles is recommended.
Severe, life-threatening, or fatal interstitial lung disease (ILD) or pneumonitis can occur in patients receiving abemaciclib and other CDK4/6 inhibitors. In patients with early breast cancer (monarchE trial, N=2,791), 3% of abemaciclib-treated patients developed any grade of ILD or pneumonitis: 0.4% were grade 3 or 4, and 1 death (0.1%) was reported. In patients with advanced or metastatic breast cancer (N=900) (MONARCH1, MONARCH2, MONARCH3 trials), 3.3% of abemaciclib-treated patients developed any grade of ILD or pneumonitis: 0.6% were grade 3 or 4, and 0.4% had a fatal outcome. Additional cases of ILD or pneumonitis, including fatal cases, have been reported in post-marketing surveillance.
Monitor patients for pulmonary symptoms suggestive of ILD or pneumonitis, which may include hypoxemia, cough, dyspnea, or interstitial infiltrates on imaging. Infectious, neoplastic, and other causes of these symptoms should be excluded by appropriate evaluations. For patients with persistent or recurrent grade 2 ILD or pneumonitis, dose interruption or dose reduction is recommended. All patients with grade 3 or 4 ILD or pneumonitis should permanently discontinue abemaciclib.
Grade ≥ 3 elevations in alanine transaminase (ALT) (incidence 2% to 6%) and aspartate transaminase (AST) (incidence 2% to 3%) have been reported in patients receiving abemaciclib. Across three clinical trials involving 3,559 patients (monarchE, MONARCH2, MONARCH3), the median time to onset of grade ≥ 3 ALT elevation was 57 to 87 days, and the median time to resolution to < grade 3 was 13 to 14 days. The median time to onset of grade ≥ 3 AST elevation was 71 to 185 days, and the median time to resolution to < grade 3 was 11 to 15 days.
Monitor liver function tests (LFTs) prior to initiating abemaciclib, every 2 weeks for the first 2 months of treatment, monthly for the next 2 months, and as clinically indicated. For patients with persistent or recurrent grade 2 hepatocellular enzyme elevations, or any grade 3 or 4 hepatocellular enzyme elevations, dose interruption, dose reduction, discontinuation, or delay in starting treatment cycles is recommended.
Across three clinical trials involving 3,559 patients (monarchE, MONARCH2, MONARCH3), the incidence of venous thromboembolic events ranged from 2% to 5% in abemaciclib-treated patients. Venous thromboembolic events included deep vein thrombosis, pulmonary embolism, pelvic vein thrombosis, cerebral venous sinus thrombosis, subclavian and axillary vein thrombosis, and inferior vena cava thrombosis. Deaths due to venous thromboembolism have been reported in abemaciclib-treated patients in clinical trials. No studies of abemaciclib have been conducted in patients with early breast cancer and a history of venous thromboembolism.
Monitor patients for signs and symptoms of venous thrombosis and pulmonary embolism, and provide appropriate medical treatment. For patients with early breast cancer who experience any grade venous thromboembolic event, and for patients with advanced or metastatic breast cancer who experience grade 3 or 4 venous thromboembolic event, dose interruption is recommended.
Based on animal studies and mechanism of action, abemaciclib can cause fetal harm when administered to pregnant women. In animal reproductive studies, administration of abemaciclib to pregnant rats during organogenesis resulted in fetal malformations and reduced fetal weights at maternal exposures (based on area under the curve [AUC]) similar to those at the maximum recommended human dose.
Pregnant women should be informed of the potential risk to the fetus. Women of reproductive potential should be advised to use effective contraception during treatment with abemaciclib and for 3 weeks after the last dose.
FDA，2025.02
