Safety and efficacy of bosutinib in fourth-line therapy of chronic myeloid leukemia patients

García‐Gutiérrez, Valentín; Milojković, Dragana; Hernández‐Boluda, Juan Carlos; Claudiani, Simone; Mateos, María Luisa Martin; Casado-Montero, Luis Felipe; González, G.; Jiménez-Velasco, Antonio; Boqué, Concepción; Martínez‐Trillos, Alejandra; Vázquez, Isabel Mata; Payer, Ángel Ramírez; Senín, Alicia; Díez, Elena Amustio; Garcia, Abelardo Barez; Carrascosa, Guiomar Bautista; Ortí, Guillermo; Ruiz, Beatriz Cuevas; Fernández, María Á.; Garay, Maria del Carmen García; Giraldo, Pilar; Castro, José María Guinea de; Rodríguez, Natalia De Las Heras; Hernán, Nuria; Pérez, Ana Iglesias; Piris-Villaespesa, Miguel; Lorenzo, José Luis López; Martí-Tutusaus, Josep M; Vallansot, Rolando; Rivas, Fernando Ortega; Puerta, Jose Manuel; Ramı́rez, Marı́a José; Romero, Esperanza; Romo, Andrés Íñiguez; Rosell, Ana; Saavedra, Silvanna Saavedra; Sebrango, Ana; Tallón, J Ríos; Valencia, Sandra Villacís; Portero, Angeles; Steegmann, Juan Luis

doi:10.1007/s00277-018-3507-2

Cited by 22 publications

(18 citation statements)

References 22 publications

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“…The Spanish CML Group (GELMC) evaluated the use of bosutinib in patients with prior failure to dasatinib and nilotinib. While the probabilities of obtaining CCyR and MMR in resistant patients were only of 25 and 14%, respectively, they increased up to 94 and 42%, respectively, in intolerant patients (50).…”

Section: Efficacy Of Tkis In Different Clinical Scenariosmentioning

confidence: 95%

Tyrosine Kinase Inhibitors Available for Chronic Myeloid Leukemia: Efficacy and Safety

García-Gutiérrez

Hernandez-Boluda

2019

Front. Oncol.

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Chronic myeloid leukemia (CML) is currently a disease in which patients can enjoy a near normal life-expectancy. However, since the majority of patients will need to remain on treatment indefinitely, physicians in care of CML patients need be familiar with the indications and toxicities of all approved tyrosine kinase inhibitors (TKI). In clinical practice, there are five TKI (imatinib, nilotinib, dasatinib, bosutinib, and ponatinib) that are available in different scenarios and have distinct safety profiles. Decisions regarding first line treatment must be based on CML risk, comorbidities, and patients expectations. Despite the excellent outcome, half of the patients will eventually fail (due to intolerance or resistance) to first line treatment, with many of them requiring a third or even further lines of therapy. When selecting for such patients, it is essential to distinguish between failure and intolerance to previous TKIs. In the present review, we will address all these issues from a practical point of view.

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Section: Efficacy Of Tkis In Different Clinical Scenariosmentioning

confidence: 95%

Tyrosine Kinase Inhibitors Available for Chronic Myeloid Leukemia: Efficacy and Safety

García-Gutiérrez

Hernandez-Boluda

2019

Front. Oncol.

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“…as first-line therapy and at 500 mg q.d. in patients who have failed prior imatinib, nilotinib, or dasatinib [174, 175]. Bosutinib is currently in multiple phase I-IV clinical trials for the treatment of several cancer types, including breast cancer, CML, NSCLC, and glioblastoma.…”

Section: Axl-targeted Therapiesmentioning

confidence: 99%

AXL receptor tyrosine kinase as a promising anti-cancer approach: functions, molecular mechanisms and clinical applications

2019

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Molecular targeted therapy for cancer has been a research hotspot for decades. AXL is a member of the TAM family with the high-affinity ligand growth arrest-specific protein 6 (GAS6). The Gas6/AXL signalling pathway is associated with tumour cell growth, metastasis, invasion, epithelial-mesenchymal transition (EMT), angiogenesis, drug resistance, immune regulation and stem cell maintenance. Different therapeutic agents targeting AXL have been developed, typically including small molecule inhibitors, monoclonal antibodies (mAbs), nucleotide aptamers, soluble receptors, and several natural compounds. In this review, we first provide a comprehensive discussion of the structure, function, regulation, and signalling pathways of AXL. Then, we highlight recent strategies for targeting AXL in the treatment of cancer.AXL-targeted drugs, either as single agents or in combination with conventional chemotherapy or other small molecule inhibitors, are likely to improve the survival of many patients. However, future investigations into AXL molecular signalling networks and robust predictive biomarkers are warranted to select patients who could receive clinical benefit and to avoid potential toxicities.

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“…Bosutinib has demonstrated activity in patients with CP-CML resistant/intolerant to multiple TKIs (imatinib, dasatinib, and nilotinib). 142,143 However, there is no clear evidence to support that switching to alternate TKI therapy would improve long-term clinical outcome for this group of patients.…”

Section: Management Of Patients With Inadequate Response To Imatinibmentioning

confidence: 99%

Chronic Myeloid Leukemia, Version 2.2021, NCCN Clinical Practice Guidelines in Oncology

Deininger

Shah

Altman³

et al. 2020

Journal of the National Comprehensive Cancer Network

165

210

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Chronic myeloid leukemia (CML) is defined by the presence of Philadelphia chromosome (Ph) which results from a reciprocal translocation between chromosomes 9 and 22 [t(9;22] that gives rise to a BCR-ABL1 fusion gene. CML occurs in 3 different phases (chronic, accelerated, and blast phase) and is usually diagnosed in the chronic phase. Tyrosine kinase inhibitor therapy is a highly effective first-line treatment option for all patients with newly diagnosed chronic phase CML. This manuscript discusses the recommendations outlined in the NCCN Guidelines for the diagnosis and management of patients with chronic phase CML.

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Safety and efficacy of bosutinib in fourth-line therapy of chronic myeloid leukemia patients

Cited by 22 publications

References 22 publications

Tyrosine Kinase Inhibitors Available for Chronic Myeloid Leukemia: Efficacy and Safety

Tyrosine Kinase Inhibitors Available for Chronic Myeloid Leukemia: Efficacy and Safety

AXL receptor tyrosine kinase as a promising anti-cancer approach: functions, molecular mechanisms and clinical applications

Chronic Myeloid Leukemia, Version 2.2021, NCCN Clinical Practice Guidelines in Oncology

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