except overall survival, patients were censored at the last follow up visit for those not known to have the respective endpoint. All patients Telatinib who received at least 1 dose of bosutinib were included in the safety analysis. Adverse events were described both with and without regard to causality.A total of 118 patients with CP CML following treatment with multiple TKIs were dosed in this study population between August 22, 2006, and March 19, 2010. All patients were previously treated with imatinib, in addition, 37 patients had dasatinib resistance, 50 had dasatinib intolerance, 27 had nilotinib resistance, 1 had nilotinib intolerance, 2 had dasatinib and nilotinib resistance, and 1 had dasatinib and nilotinib intolerance. Demographic and baseline disease characteristics are summarized in Table 1.
Twenty patients had Philadelphia chromosome variants or additional karyotypic abnormalities at the time of screening, with abnormalities affecting chromosome 8 being the most common. Bcr Abl mutation status at baseline was available for 83 patients, and 39 of these had at least 1 mutation identified, with 9 harboring more than P450 Inhibitors 1 mutation. As of the data cutoff on March 28, 2011, the median duration of follow up was 28.5 months. The median duration on bosutinib treatment asenapine structure was 8.3 months and varied between 7.3 months for dasatinib resistant patients and 11.0 months for nilotinib resistant patients. The median dose intensity was 478 mg/day. Dose interruptions were required for 70% of patients. During the study, 20 patients had their dose of bosutinib escalated to 600 mg/day for lack of efficacy.
As of the data cutoff, 29% of patients were still receiving bosutinib, reasons for discontinuation of treatment are shown in Table 2.MCyR was attained by 32% of Rolipram solubility patients, with CCyR in 24% of patients, including 1 of 3 patients who were previously treated with all 3 TKIs, an additional 6% of patients achieved a minor cytogenetic response. Of note, patients with CCyR or PCyR at baseline were considered non responders for this analysis despite potential maintenance of their response. When patients with a baseline CCyR or PCyR who maintained their response post baseline were included as responders in the analysis, the rates of MCyR and CCyR were 39% and 31%, respectively. Median time to MCyR among responders was 12.4 weeks.
Kaplan Meier median durations of MCyR and CCyR had not yet been reached overall and for most subpopulations, with overall estimates of 59% and 51% for the Kaplan Meier probability of retaining MCyR and CCyR at 2 years, respectively. The Kaplan Meier probability of retaining MCyR at 2 years was high among summary patients with nilotinib resistance and dasatinib intolerance, but lower among those with dasatinib resistance and nilotinib intolerance/prior treatment with all 3 TKIs. Of the 29 patients who achieved MCyR by 24 weeks, 16 retained their response at 72 weeks and 9 retained their response at 96 weeks as of the data snapshot, 4 of these 29 patients have not yet reached their week 72 evaluation and are thus considered not to have retained their response at weeks 72 and 96.A confirmed CHR was achieved or maintained by 85 patients. Of the 68 subjects who did not have a CHR at baseline, 44 achieved a confirmed CHR. Of the 85 patients who achieved.
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