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Letters to the Editor
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Figure 1. Anti-tumor activity and pharmacokinetics of abemaciclib. (A) Change in tumor size at best response. Best overall response was based on investigator assessment. Number above or below each bar is the number of treatment regimens prior to study entry. Cyclin D1 expression and t(11;14)(q13;q32) transloca- tion in each patient is shown below the response. (B) Abemaciclib plasma concentration-time profiles following oral administration of single (left panel) and mul- tiple (right panel) doses of 200 mg abemaciclib every 12 hours, depicted as individual (gray continuous lines) and geometric mean (black broken line).
for Adverse Events (CTCAE) v4.0. The most frequent treatment-emergent adverse event (TEAE) of any grade were diarrhea, thrombocytopenia, fatigue and neutrope- nia (Table 2). Diarrhea was the most common TEAE and was reported by 75% of the patients with most (60.7%) experiencing low grade diarrhea (grade 1 or 2) in cycle 1. Grade 3 diarrhea occurred less frequently (14.3%). Per protocol, diarrhea was managed with over-the-counter medications, such as loperamide, or dose reduction. 12.5% of patients required dose reduction due to diar- rhea, and no patient discontinued due to this adverse event. 50% of the patients who experienced diarrhea received anti-diarrheal medication (loperamide). Fatigue was also predominantly of low grade; grade 3 and 4 events were reported for thrombocytopenia (n=11) and
neutropenia (n=9) and were likely related to study drug. A total of 42.9% of the patients reported at least 1 serious adverse event (SAE). Five patients experienced grade ≥3 events, likely related to the study drug (n=1 each of lobar pneumonia and lung infection, dehydration and pyrexia, nausea, grade 5 sepsis, and somnolence). There were five fatal events reported that were considered by investiga- tors as due to AE (one patient due to grade 5 meningitis that was unrelated to the study drug, one patient due to grade 5 sepsis possibly related to the study drug, one patient due to grade 4 sepsis unrelated to the study drug, one patient due to grade 5 reversible posterior leukoen- cephalopathy unrelated to the study drug, and one patient due to grade 3 lung infection possibly related to the study drug; Online Supplementary Figure S3).
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haematologica | 2021; 106(3)