Exposure–response analysis for key safety endpoints
thrombocytopenia, neutropenia, diarrhea
THROMBOCYTOPENIA, REGRESSION, EVENT, NEUTROPENIA
For all safety endpoints, Grade 0 (no event) was the most frequent observed grade. The exception was diarrhea, with 41.3% of patients having Grade 1 and 29.3% having Grade 0 (Table Predicted probability of (A) diarrhea grade with For safety endpoints of incidence of elevated ALT, neutropenia, and thrombocytopenia, no significant exposure–response relationship was identified using ordinal logistic regression. To further evaluate these safety endpoints, binary logistic regression was performed at different AE grades (i.e., Grade >0, Grade >1, or Grade >2). No significant exposure–response relationship between bosutinib exposure and incidence of any grade AE was observed for elevated ALT and neutropenia. However, a significant exposure–response relationship was identified between thrombocytopenia Grade >2 and Final logistic regression equation:For the incidence of thrombocytopenia, patients had an increased probability of an AE Grade >2 with increasing bosutinib exposure and a decreased probability of an AE Grade >2 with increasing age (Figure 