Can Verzenio (abemaciclib) cause diarrhea in an adult female patient with a history of breast cancer?

Does Verzenio Cause Diarrhea?

Yes, Verzenio (abemaciclib) causes diarrhea in the vast majority of patients, with diarrhea being the most frequent adverse event occurring in 81-90% of patients. 1

Incidence and Severity

Diarrhea occurs in approximately 81-90% of patients taking abemaciclib, making it the single most common side effect of this medication. 1, 2

• Grade 3 diarrhea (severe) occurs in approximately 9-10% of patients 1
• Grade 4 diarrhea is rare but can occur 3
• The diarrhea is typically early-onset and dose-dependent 4
• In the MONARCH 1 trial, 90.2% of patients experienced diarrhea of any grade 1
• In the MONARCH 3 trial, 81.3% of patients in the abemaciclib arm experienced diarrhea compared to 29.8% in the placebo arm 1, 2

Clinical Impact on Quality of Life

The diarrhea from abemaciclib is both statistically significant and clinically meaningful, representing the only symptom that crosses the threshold for clinically meaningful impact on quality of life. 1

• Patients on abemaciclib reported an 18.68-point worse diarrhea score compared to placebo (P < .001), exceeding the 10-point threshold for clinical significance 1
• Time to sustained deterioration for diarrhea was significantly shorter in abemaciclib-treated patients (hazard ratio 1.74; 95% CI 1.25-2) 1
• Despite the high incidence of diarrhea, 83.8% of cases were effectively managed with dose modifications and antidiarrheal medications 1

Management Protocol from FDA Label

At the first sign of loose stools, immediately start antidiarrheal agents and increase oral fluid intake. 3

Dose Modification Algorithm for Diarrhea:

• Grade 1 diarrhea: Continue abemaciclib at current dose 3

• Grade 2 diarrhea:

  • If resolves within 24 hours to ≤Grade 1: Continue same dose 3
  • If persists beyond 24 hours: Suspend dose until resolution, then resume at same dose 3
  • If persists or recurs despite maximal supportive measures: Suspend until ≤Grade 1, then resume at next lower dose 3

• Grade 3 or 4 diarrhea, or requires hospitalization: Suspend dose until toxicity resolves to ≤Grade 1, then resume at next lower dose 3

Prophylactic Management

Prophylactic loperamide does not significantly reduce the incidence or severity of abemaciclib-induced diarrhea. 4

• In the nextMONARCH trial, abemaciclib 200 mg with prophylactic loperamide showed similar diarrhea rates (62.3%; grade 3: 7.8%) compared to abemaciclib 150 mg without prophylaxis (67.1%; grade 3: 3.8%) 4
• Reactive management with dose reductions and antidiarrheal medications is the standard approach rather than prophylaxis 4

Important Clinical Caveats

The diarrhea is predominantly Grade 1 (mild) in most patients, with 44.6% experiencing only Grade 1 diarrhea in the MONARCH 3 trial. 2

Diarrhea management does not compromise efficacy when dose reductions are appropriately implemented. 4

This differs from neratinib, another breast cancer agent that also causes substantial diarrhea but requires mandatory diarrhea prophylaxis from the start of therapy. 1