Safety and efficacy of bosutinib (SKI-606) in chronic phase Philadelphia chromosome–positive chronic myeloid leukemia patients with resistance or intolerance to imatinib

Cortes, Jorge; Kantarjian, Hagop M.; Brümmendorf, Tim H.; Kim, Dong Wook; Turkina, Anna; Shen, Zhi Xiang; Pasqüini, Ricardo; Khoury, H. Jean; Arkin, Steven; Volkert, Angela; Besson, Nadine; Abbas, Richat; Wang, Junyuan; Leip, Eric; Gambacorti‐Passerini, Carlo

doi:10.1182/blood-2011-05-355594

Cited by 412 publications

(462 citation statements)

References 30 publications

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“…Bosutinib was initially studied in patients that were resistant to or intolerant of imatinib [61]. After a dose escalation period, 500 mg once daily was selected to go forward as the phase II dose, with the potential for dose escalation to 600 mg once daily for patients not meeting prespecified benchmarks.…”

Section: Second and Third Generation Tkismentioning

confidence: 99%

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Chronic myeloid leukemia: 2014 update on diagnosis, monitoring, and management

2014

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Disease overview: Chronic Myeloid Leukemia (CML) is a myeloproliferative neoplasm with an incidence of 1–2 cases per 100,000 adults, and accounts for ∼15% of newly diagnosed cases of leukemia in adults. Diagnosis: CML is characterized by a balanced genetic translocation, t(9;22)(q34;q11.2), involving a fusion of the Abelson oncogene (ABL) from chromosome 9q34 with the breakpoint cluster region (BCR) gene on chromosome 22q11.2. This rearrangement is known as the Philadelphia chromosome. The molecular consequence of this translocation is the generation of a BCR‐ABL fusion oncogene, which in turn translates into a Bcr‐Abl oncoprotein. Frontline therapy: Three tyrosine kinase inhibitors (TKIs), imatinib, nilotinib, and dasatinib have been approved by the US Food and Drug Administration for the first‐line treatment of patients with newly diagnosed CML in chronic phase (CML‐CP). Clinical trials with second generation TKIs reported significantly deeper and faster responses; their impact on long‐term survival remains to be determined. Salvage therapy: For patients who fail frontline therapy, second‐line options include second and third generation TKIs. Although second and third generation TKIs are potent and specific BCR‐ABL TKIs, they exhibit unique pharmacological profiles and response patterns relative to different patient characteristics, such as patients comorbidities, disease stage, and BCR‐ABL mutational status. Patients who develop the T315I “gatekeeper” mutation display resistance to all currently available TKIs except ponatinib. Allogeneic transplantation remains an important therapeutic option for CML‐CP who have failed at least 2 TKIs, and for all patients in advanced phase disease. Am. J. Hematol. 89:547–556, 2014. © 2014 Wiley Periodicals, Inc.

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Section: Second and Third Generation Tkismentioning

confidence: 99%

“…The available data also indicate that bosutinib can be used for patients with most known mutations that lead to imatinib failure [61]. Like dasatinib and nilotinib, bosutinib lacks activity against T315I.…”

Section: How To Select a Second Or Third Line Optionmentioning

confidence: 99%

Chronic myeloid leukemia: 2014 update on diagnosis, monitoring, and management

2014

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“…It sustains activity against most mutations related with imatinib resistance except V299L and T315I. Bosutinib has shown significant activity in patients in CML-CP post imatinib failure; the rates of complete hematologic and cytogenetic responses were 86% and 41%, respectively [35]. The 2-year PFS and OS rates were 79% and 92%, respectively.…”

Section: Bosutinibmentioning

confidence: 81%

Chronic myeloid leukemia: First‐line drug of choice

Jabbour

2015

American J Hematol

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The advent of tyrosine kinase inhibitors (TKIs) has drastically changed the treatment outcome of chronic myeloid leukemia (CML). Imatinib was the first TKI approved, and has been considered the standard of care for more than a decade. Second generation compounds, namely dasatinib and nilotinib, are highly effective in newly diagnosed patients as well as those who fail imatinib. Second generation TKIs have been demonstrated to induce deeper and faster responses compared to imatinib, however no survival advantage has been observed so far. Today, the expected survival of CML patients, if properly managed, is likely to be similar to the general population. Clinicians are faced the challenge of making decision for which TKI to choose upfront. Comorbidities of the patient, the side effect profile, and the cost of the TKI of interest should be an important consideration in decision making. Whatever TKI is chosen as frontline, noncompliance or treatment failure should be recognized early as a prompt intervention increases the chance of achieving best possible response. Herein, we review the frontline options for the management of patients with CML and how to best choose these agents.

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“…In newly diagnosed patients with CML, increasing liver enzymes were associated with a significantly increased rate of treatment discontinuation with bosutinib compared with imatinib [52,74]. However it is worth noting that a successful rechallenge was carried out in nearly 75% of cases [17].…”

Section: Bosutinibmentioning

confidence: 99%

Chronic myeloid leukemia: Second‐line drugs of choice

Gambacorti‐Passerini

Cordani

2015

American J Hematol

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The efficacy of second-line treatment for chronic myeloid leukemia (CML) plays an important role in allowing CML patients to enjoy a normal life expectancy. Four tyrosine kinase inhibitors (TKIs) are presently available: bosutinib, dasatinib, nilotinib, ponatinib. Each one has different safety and activity profiles, which are reviewed here. No controlled studies are available to guide treatment decision, which must be based on the characterization of leukemic cells, especially in cases of resistance to TKI, coupled with the safety profile of each TKI. Patient comorbidities also play an important role in the treatment decision, which can achieve a new durable response in over 50% of treated patients.

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Safety and efficacy of bosutinib (SKI-606) in chronic phase Philadelphia chromosome–positive chronic myeloid leukemia patients with resistance or intolerance to imatinib

Cited by 412 publications

References 30 publications

Chronic myeloid leukemia: 2014 update on diagnosis, monitoring, and management

Chronic myeloid leukemia: 2014 update on diagnosis, monitoring, and management

Chronic myeloid leukemia: First‐line drug of choice

Chronic myeloid leukemia: Second‐line drugs of choice

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