scholarly journals Bosutinib Versus Imatinib for Newly Diagnosed Chronic Myeloid Leukemia: Results From the Randomized BFORE Trial

2018 ◽  
Vol 36 (3) ◽  
pp. 231-237 ◽  
Author(s):  
Jorge E. Cortes ◽  
Carlo Gambacorti-Passerini ◽  
Michael W. Deininger ◽  
Michael J. Mauro ◽  
Charles Chuah ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Philadelphia Chromosome ◽  
Chronic Phase ◽  
Hazard Ratio ◽  
Line Treatment ◽  
Newly Diagnosed ◽  
First Line ◽  
First Line Treatment ◽  
Philadelphia Chromosome Positive

Purpose Bosutinib is a potent dual SRC/ABL kinase inhibitor approved for adults with Philadelphia chromosome–positive chronic myeloid leukemia (CML) resistant and /or intolerant to prior therapy. We assessed the efficacy and safety of bosutinib versus imatinib for first-line treatment of chronic-phase CML. Methods In this ongoing, multinational, phase III study, 536 patients with newly diagnosed chronic-phase CML were randomly assigned 1:1 to receive 400 mg of bosutinib once daily (n = 268) or imatinib (n = 268). Per protocol, efficacy was assessed in patients who were Philadelphia chromosome–positive with typical (e13a2/e14a2) transcripts (bosutinib, n = 246; imatinib, n = 241). Patients with Philadelphia chromosome–negative–/ BCR-ABL1–positive status and those with unknown Philadelphia chromosome status and/or atypical BCR-ABL1 transcript type were excluded from this population. Results The major molecular response (MMR) rate at 12 months (primary end point) was significantly higher with bosutinib versus imatinib (47.2% v 36.9%, respectively; P = .02), as was complete cytogenetic response (CCyR) rate by 12 months (77.2% v 66.4%, respectively; P = .0075). Cumulative incidence was favorable with bosutinib (MMR: hazard ratio, 1.34; P = .0173; CCyR: hazard ratio, 1.38; P < .001), with earlier response times. Four patients (1.6%) receiving bosutinib and six patients (2.5%) receiving imatinib experienced disease progression to accelerated/blast phase. Among treated patients, 22.0% of patients receiving bosutinib and 26.8% of patients receiving imatinib discontinued treatment, most commonly for drug-related toxicity (12.7% and 8.7%, respectively). Grade ≥ 3 diarrhea (7.8% v 0.8%) and increased ALT (19.0% v 1.5%) and AST (9.7% v 1.9%) levels were more common with bosutinib. Cardiac and vascular toxicities were uncommon. Conclusion Patients who received bosutinib had significantly higher rates of MMR and CCyR and achieved responses faster than those who received imatinib. Consistent with the known safety profile, GI events and transaminase elevations were more common with bosutinib. Results indicate bosutinib may be an effective first-line treatment for chronic-phase CML.

scholarly journals Efficacy and Safety of Generic Dasatinib As First-Line Treatment in Patients with Chronic Myeloid Leukemia in Chronic Phase: Final Analysis with 2-Year Follow-up

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 3616-3616
Author(s):  
Jie Jin ◽  
Li Meng ◽  
Wenjuan Yu ◽  
Peng Liu ◽  
Xin Du ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Primary Endpoint ◽  
Myeloid Leukemia ◽  
Chronic Phase ◽  
Line Treatment ◽  
Newly Diagnosed ◽  
Efficacy And Safety ◽  
First Line ◽  
First Line Treatment

Abstract Purpose: Generic dasatinib, a second-generation tyrosine kinase inhibitor (TKI), was approved as a second-line treatment for chronic myeloid leukemia (CML) patients in chronic phase (CP) in china. We initiated a prospective, multi-center and single-arm clinical trial (NCT04925141) from May 2016 to October 2018 to evaluate efficacy and safety of generic dasatinib as first-line treatment in China. The primary endpoint was achieved, here we reported the 2 years follow-up results to see its long-term clinical benefit in Chinese patients. Methods:The study included the newly diagnosed CML-CP patients who was diagnosed by the presence of Philadelphia (Ph) chromosome and/or presence of BCR-ABL fusion gene. Key inclusion criteria were as follows: 1) Age ≥ 18 years; 2) The CML subjects in chronic phase with the Ph+ definitive diagnosis were within 6 months before the onset of administration of the study drug; 3) The ECOG performance grades of 0-2; 4) Sufficient main organ functions. All newly diagnosed patients were given 100mg/d (initial dose) of the generic dasatinib. The primary endpoint was molecular major response (MMR) calculated based on the BCR-ABL1 ≤ 0.1% at the 12th month. Secondary endpoints were proportion of subjects who achieved and maintained MMR at 3, 6, and 18 months; Cumulative MMR rates at 6, 12, and 24 months were determined. All patients were followed up through the hospital outpatient departments at second, fourth and eighth weeks, and third, sixth, ninth, twelfth, eighteenth, and twenty-fourth months. The follow-up ended on December 6, 2019. The SAS 9.2 software was utilized for all statistical analyses in this study, and the two-sided test was performed to see variances. Results: A total of 59 patients were included in this trail, with median age of 44 (19 - 70), and 7% of the subjects were at high risk based on the Sokal index for the disease prognosis. The primary endpoint MMR rate at the 12th month was 80.8% which had been published. At 12 months, the cumulative response rate (CCyR) was 85.5% (47/55) and the cumulative MMR was 76.4% (42/55). Here we are reporting the 2 years follow ups. At 24 months, the complete hematological response (CHR) was 88.4%, the cumulative MMR rate was 73.7%, the cumulative MR4.0 rate was 63.6%, the cumulative MR4.5 rate was 58.2%, and the cumulative complete molecular response (CMR) rate was 58.2%. The most common adverse events (AEs) was thrombocytopenia (42.4%) in hematology and pleural effusion (20.3%) in non-hematology, only 11.9% and 1.7% of whom were grade III~IV respectively. Conclusion: This was the first report on domestic dasatinib as the first-line treatment for CML-CP patients received a clinical benefit with 24 months in China. Safety was similar with that of the original study data. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Is EUTOS Score Predictive Of Outcome In Patients With Early Chronic Phase Chronic Myeloid Leukemia Treated With Imatinib? Preliminary Data From The National Protocol Of The Chilean Cooperative Group Panda

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5196-5196 ◽  
Author(s):  
Javier Zelada ◽  
Marisa Pia Aida Capurro ◽  
Bernardita Rojas ◽  
Lilian M Pilleux ◽  
Augusto Aspillaga ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Predictive Value ◽  
Myeloid Leukemia ◽  
Chronic Phase ◽  
Cytogenetic Response ◽  
Cooperative Group ◽  
Line Treatment ◽  
First Line ◽  
Eutos Score ◽  
First Line Treatment

Abstract Background Before the Tirosine Kinase Inhibitors (TKI) era, the SOKAL and HASFORD scores have been used to predict outcome in chronic myeloid leukemia (CML) patients. The recently reported European Treatment and Outcome Study (EUTOS) score is a simple formula created to identify patients with significantly lower probabilities of responding to therapy and survival. The MD Anderson group didn´t validate this score. Aims To validate the EUTOS score in our population treated in the public health hospitals in Chile with a single protocol of the cooperative group PANDA. Methods Patients were selected from the data base of the CML 2007 PANDA protocol. All patients were adults (>15 years old) in early chronic phase and received first-line treatment with imatinib-based regimes and had a minimal follow up of twelve months. Event was defined as not reaching complete cytogenetic response in the first year of treatment, death from any cause at any time, loss of complete hematologic response, loss of major cytogenetic response, or progression to accelerated or blast phase. Overall survival (OS) was defined as death of any cause at any time. Event free survival (EFS) was defined as time from diagnosis to any event. Results A total of 78 patients were selected from the 330 patients of the data base. The rest had incomplete data. The median age was 48 (range 16 to 79 years old), 47 men and 31 women. Patients with low EUTOS score were 49 (63%) and 29 (37%) were high. The sensitivity of EUTOS was 46% , the specificity was 71% and the negative predictive value was 68%. There was no significative difference in EFS and OS in both EUTOS groups. Conclusions EUTOS score was not predictive of outcome in our patient population. Nevertheless it showed a good negative predictive value meaning that it can only identify low risk patients. This could be used in developing countries to select patients that could use lower cost TKI in first line treatment. Disclosures: No relevant conflicts of interest to declare.

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