Safety
toxicity, toxicities, gastrointestinal (GI) toxicity
ADVERSE EVENTS, ADVERSE EVENT
The primary analysis data set included 53 pts who received at least 14 daily doses of bosutinib. Per protocol, four pts receiving bosutinib only for 11, 12, 12 and 10 days, respectively, were excluded from further analysis. Three additional pts had to be excluded due to an insufficient observation time (i.e., < 6 months). As a consequence, 50 out of the total of 57 enrolled pts were eligible for primary endpoint analysis. Twenty pts (40%) did not develop any clinically relevant GI toxicity > grade 1 during the first 6 months including 6 pts (11%), who did not develop any grade of GI toxicities. The overall rate of grade 2 to 4 GI toxicity within the first 6 months of treatment was 60% (95% CI: 45–74%). Thus, the null hypothesis of the trial (GI toxicity was assumed to be reduced to < 40%) could not be discarded. Remarkably, GI toxicity led to treatment discontinuation in only one patient keeping in mind that only 60% could successfully increase the dose to 500 mg. Rates of grade 2 to 4 GI toxicity within the first 12 and 24 months of treatment in the primary analysis data set were 65% and 72%, respectively, showing that most of the higher grades GI toxicity happened during the first six months (see Fig. Cumulative incidence of grade 2 to 4 gastrointestinal (GI) toxicity in the primary analysis data set (Adverse events led to dose reduction in 53% (The most common AEs leading to discontinuation were elevation of liver enzyme serum levels (i.e., ALT increased The most frequently reported adverse events including corresponding G3/4 AEs and details on GI toxicityLegend: *According to the MedDRA Preferred Term; in the overall patient population (