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Practical management of toxicities associated with bosutinib in patients with Philadelphia chromosome-positive chronic myeloid leukemia.

ABSTRACT: Bosutinib (SKI-606) is an oral, dual Src/Abl tyrosine kinase inhibitor (TKI) approved for treatment of patients with Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) that is resistant or intolerant to prior TKI therapy or for whom other TKIs are not appropriate choices. The objective of this review is to provide a longitudinal summary of toxicities that may arise during treatment with second-line or later bosutinib in patients with Ph+ chronic phase CML and to provide strategies for managing these toxicities. As bosutinib is not currently indicated for newly diagnosed CML, toxicities associated with first-line treatment are not reviewed. Recognition and optimal management of these toxicities can facilitate patient compliance and affect treatment outcomes.

SUBMITTER: Khoury HJ

PROVIDER: S-EPMC5888919 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

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Practical management of toxicities associated with bosutinib in patients with Philadelphia chromosome-positive chronic myeloid leukemia.

Khoury H J HJ Gambacorti-Passerini C C Brümmendorf T H TH

Annals of oncology : official journal of the European Society for Medical Oncology 20180301 3

Bosutinib (SKI-606) is an oral, dual Src/Abl tyrosine kinase inhibitor (TKI) approved for treatment of patients with Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) that is resistant or intolerant to prior TKI therapy or for whom other TKIs are not appropriate choices. The objective of this review is to provide a longitudinal summary of toxicities that may arise during treatment with second-line or later bosutinib in patients with Ph+ chronic phase CML and to provide strate ...[more]

PMID: 29385394

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Project description:Abstract Tyrosine kinase inhibitors (TKIs) have significantly changed the treatment of chronic myeloid leukemia (CML) and improved outcomes for patients with CML in chronic phase (CML-CP) and accelerated phase (AP). Now armed with numerous effective therapeutic options, clinicians must consider various patient- and disease-specific factors when selecting the most appropriate TKI across lines of therapy. While most patients with CML expected to have a near-normal life expectancy due to the success of TKIs, emphasis has expanded beyond response and survival to include factors like quality of life, tolerability, and long-term toxicity management. Importantly, a subset of patients can achieve sustained deep molecular response and can attain treatment-free remission. Despite these successes, unmet needs remain related to CML treatment, including the persistent challenge of treatment resistance and intolerance, broadening treatment options for patients with resistance mutations or serious comorbidities, and focus on specific populations such as children and young adults. In particular, the only previously available treatments for patients with CML-CP with the T315I mutation were ponatinib, olverembatinib (exclusively approved for use in China at the time of this writing), omacetaxine, and hematopoietic stem cell transplantation. Asciminib has entered the CML treatment landscape as a new option for adult patients with CML-CP who have received ≥2 prior TKIs or those with the T315I mutation. Asciminib’s unique mechanism of action, Specifically Targeting the ABL Myristoyl Pocket, sets it apart from traditional adenosine triphosphate-competitive TKIs. While asciminib may overcome unmet needs for patients with CML-CP and continues to be studied in other novel settings, guidance on how to integrate asciminib in treatment algorithms is needed. This review focuses on clinical data and how asciminib can overcome current unmet needs, discusses how to individualize patient selection, and highlights future directions to investigate asciminib in earlier lines of therapy and in children and adolescents.

Project description:BACKGROUND:Health-related quality of life (HRQOL) in patients with chronic-phase chronic myeloid leukemia (CML) is important because of the requirement for long-term treatment. This study assessed HRQOL in bosutinib-treated patients with Philadelphia chromosome-positive CML and resistance or intolerance to 1 (chronic-phase second-line [CP2L]) or more (chronic-phase third-line [CP3L]) tyrosine kinase inhibitors who had 264 weeks or more of follow-up (ClinicalTrials.gov identifier NCT00261846). METHODS:Patient-reported HRQOL was assessed with the EuroQol 5-Dimensions Questionnaire (EQ-5D) and the Functional Assessment of Cancer Therapy-Leukemia (FACT-Leu). RESULTS:In total, 284 and 119 patients composed the CP2L and CP3L cohorts, respectively. At treatment completion, more than 50% of the patients in the CP2L and CP3L cohorts completed the EQ-5D and FACT-Leu assessments. The EQ-5D and EQ-5D visual analog scale scores were stable in both cohorts throughout treatment. The mean FACT-Leu scores were generally stable over time but were lower in magnitude in the CP3L cohort versus the CP2L cohort. The FACT-Leu scale scores of a subset of patients with chronic diarrhea (CP2L, n?=?101; CP3L, n?=?30) were similar to the scores of the larger cohorts. Minimally important differences (MIDs) from baseline for the FACT-Leu scale scores were observed for the following: emotional well-being (EWB), Functional Assessment of Cancer Therapy-General (FACT-G) Total, FACT-Leu Total, and Functional Assessment of Cancer Therapy Trial Outcome Index (FACT-TOI) in the CP2L cohort and FACT-Leu Total in the CP3L cohort. Among patients with chronic diarrhea, MIDs were observed for EWB, FACT-G Total, FACT-Leu Total, and FACT-TOI in the CP2L cohort and for EWB, FACT-G Total, and FACT-Leu Total in the CP3L cohort. CONCLUSIONS:HRQOL was maintained with long-term bosutinib treatment for patients with CP2L and CP3L CML. Cancer 2018;124:587-95. © 2017 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

Dataset Information

Practical management of toxicities associated with bosutinib in patients with Philadelphia chromosome-positive chronic myeloid leukemia.

Publications

Practical management of toxicities associated with bosutinib in patients with Philadelphia chromosome-positive chronic myeloid leukemia.

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