Second‐ or third‐generation tyrosine kinase inhibitors in first‐line treatment of chronic myeloid leukemia in general population: Is there a real benefit?

Canet, Jim; Cony‐Makhoul, Pascale; Orazio, Sébastien; Cornet, Édouard; Troussard, Xavier; Maynadié, Marc; Étienne, Gabriel; Monnereau, Alain

doi:10.1002/cam4.4186

Cited by 7 publications

(6 citation statements)

References 32 publications

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“…In a retrospective French study on 507 patients diagnosed with CML between 2006 and 2016, 388 (76.5%) received imatinib and 114 (22.5%) received nilotinib or dasatinib as frontline treatment. 15 Similar figures emerged from the real-life study conducted between 2015 and 2017 in 257 patients treated at 21 tertiary centers and general hospitals in the United Kingdom, where imatinib was the frontline TKI in most patients (79%). 16 The reasons for the TKI choice were recorded for fewer than half of the patients and seemed to be a result of physicians' preference for a "standard" approach.…”

Section: Odds Ratio 95% Confidence Interval Psupporting

confidence: 55%

“…The results of this observational study demonstrate that approximately 55% of Italian patients newly diagnosed with CP‐CML in the last decade received imatinib as a frontline therapy. In a retrospective French study on 507 patients diagnosed with CML between 2006 and 2016, 388 (76.5%) received imatinib and 114 (22.5%) received nilotinib or dasatinib as frontline treatment 15 . Similar figures emerged from the real‐life study conducted between 2015 and 2017 in 257 patients treated at 21 tertiary centers and general hospitals in the United Kingdom, where imatinib was the frontline TKI in most patients (79%) 16 .…”

Section: Discussionmentioning

confidence: 62%

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Determinants of frontline tyrosine kinase inhibitor choice for patients with chronic‐phase chronic myeloid leukemia: A study from the Registro Italiano LMC and Campus CML

Tiribelli

Latagliata

Breccia

et al. 2023

Cancer

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BackgroundImatinib, dasatinib, and nilotinib are tyrosine kinase inhibitors (TKIs) approved in Italy for frontline treatment of chronic‐phase chronic myeloid leukemia (CP‐CML). The choice of TKI is based on a combined evaluation of the patient’s and the disease characteristics. The aim of this study was to analyze the use of frontline TKI therapy in an unselected cohort of Italian patients with CP‐CML to correlate the choice with the patient’s features.MethodsA total of 1967 patients with CP‐CML diagnosed between 2012 and 2019 at 36 centers throughout Italy were retrospectively evaluated; 1089 patients (55.4%) received imatinib and 878 patients (44.6%) received a second‐generation (2G) TKI.ResultsSecond‐generation TKIs were chosen for most patients aged <45 years (69.2%), whereas imatinib was used in 76.7% of patients aged >65 years (p < .001). There was a predominant use of imatinib in intermediate/high European long–term survival risk patients (60.0%/66.0% vs. 49.7% in low‐risk patients) and a limited use of 2G‐TKIs in patients with comorbidities such as hypertension, diabetes, chronic obstructive pulmonary disease, previous neoplasms, ischemic heart disease, or stroke and in those with >3 concomitant drugs. We observed a greater use of imatinib (61.1%) in patients diagnosed in 2018–2019 compared to 2012–2017 (53.2%; p = .002). In multivariable analysis, factors correlated with imatinib use were age > 65 years, spleen size, the presence of comorbidities, and ≥3 concomitant medications.ConclusionsThis observational study of almost 2000 cases of CML shows that imatinib is the frontline drug of choice in 55% of Italian patients with CP‐CML, with 2G‐TKIs prevalently used in younger patients and in those with no concomitant clinical conditions. Introduction of the generic formulation in 2018 seems to have fostered imatinib use.

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Section: Odds Ratio 95% Confidence Interval Psupporting

confidence: 55%

Section: Discussionmentioning

confidence: 62%

Determinants of frontline tyrosine kinase inhibitor choice for patients with chronic‐phase chronic myeloid leukemia: A study from the Registro Italiano LMC and Campus CML

Tiribelli

Latagliata

Breccia

et al. 2023

Cancer

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“…Although data on real-world use of first-, second-, and third-generation tyrosine kinase (TKI) inhibitors in chronic myeloid leukemia (CML) in the elderly are scarce, the analysis of available data suggests that such CML patients have an excellent prognosis and survival benefit, indistinguishable from that of younger patients [ 5 , 25 – 30 ], as our data show.…”

Section: Discussionmentioning

confidence: 62%

Efficacy and safety of nilotinib as frontline treatment in elderly (> 65 years) chronic myeloid leukemia patients outside clinical trials

et al. 2023

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Here, we report real-world evidence on the safety and efficacy of nilotinib as a first-line treatment in elderly patients with chronic phase CML, treated in 18 Italian centers. Sixty patients aged > 65 years (median age 72 years (65–84)) were reported: 13 patients were older than 75 years. Comorbidities were recorded at baseline in 56/60 patients. At 3 months of treatment, all patients obtained complete hematological response (CHR), 43 (71.6%) an early molecular response (EMR), while 47 (78%) reached a complete cytogenetic response (CCyR). At last follow-up, 63.4% of patients still had a deep molecular response (MR4 or better), 21.6% reached MR3 as best response and 11.6% persisted without MR. Most patients (85%) started the treatment at the standard dose (300 mg BID), maintained at 3 months in 80% of patients and at 6 months in 89% of them. At the last median follow-up of 46.3 months, 15 patients discontinued definitively the treatment (8 due to side effects, 4 died for unrelated CML causes, 1 for failure, 2 were lost to follow-up). One patient entered in treatment-free remission. As to safety, 6 patients (10%) experienced cardiovascular events after a median time of 20.9 months from the start. Our data showed that nilotinib could be, as first-line treatment, effective and relatively safe even in elderly CML patients. In this setting, more data in the long term are needed about possible dose reduction to improve the tolerability, while maintaining the optimal molecular response.

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“…TKIs have only mild non-specific toxicity, and due to safety concerns, they can be used in combination with other therapeutic modalities such radiation, chemotherapy, and immune-based therapies. TKIs have had positive outcomes in the management and care of patients ( Tables 1 – 4 ) ( Bhullar et al, 2018 ; Canet et al, 2021 ). TKs are implicated in several malignancies and are classified into two types, such as receptor protein kinases (RTKs) and non-receptor protein kinases (NRTKs), When ligands bind to activated RTKs, they act as cell-surface signal transducers ( Siveen et al, 2018 ).…”

Section: Receptor Tyrosine Kinasesmentioning

confidence: 99%

Clinical updates on tyrosine kinase inhibitors in HER2-positive breast cancer

2022

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Breast cancer (BC) is caused by epigenetic modifications and genetic heterogeneity and exhibits various histological feature. HER2+ (Human epidermal growth factor receptor 2) is a more aggressive type of breast cancer, diagnosis and prognosis are difficult for HER2+ BC. Anti-HER2+ inhibitors have been effectively used for patient treatment. High mortality rate is reported in HER2+ BC, due to availability of limited therapeutic options. Despite advances in systemic medications to treat metastatic breast cancer (MBC), HER2-positive MBC is still challenging for patients and treating clinicians. The clinical characteristics of the disease have changed after treatment with HER2-targeted therapy. Various types of Tyrosine kinase inhibitors (TKIs) have been developed to treat patients with HER2+ BC including afatinib, lapatinib, neratinib, tucatinib, and pyrotinib, have been developed as HER2-targeted therapies. The antibody-drug conjugates adotrastuzumab, emtansine, famtrastuzumab, and deruxtecan, as well as the anti-HER2 monoclonal antibody pertuzumab are used in both early-stage and metastatic situations, either alone or in conjunction with chemotherapy and other HER2-targeting therapies. The emergence of drug resistance in anti-HER2 therapies has been observed. To overcome drug resistance and limited efficacy in current treatment options, nano formulations can be used in patients with HER2+ BC treatment. Anti-HER2 ligands can be used in various nano formulations to target HER2 receptors. Here we will discuss, targeted TKIs in patients with HER2+ BC, clinical studies of HER2+ targeted TKIs, mechanisms of resistance to HER2-directed therapies with new implications of TKIs in HER2+ MBC (metastatic breast cancer) and anti-HER2 ligand in various nano formulations to target HER2 receptors.

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Second‐ or third‐generation tyrosine kinase inhibitors in first‐line treatment of chronic myeloid leukemia in general population: Is there a real benefit?

Abstract: This is an open access article under the terms of the Creat ive Commo ns Attri bution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 7 publications

References 32 publications

Determinants of frontline tyrosine kinase inhibitor choice for patients with chronic‐phase chronic myeloid leukemia: A study from the Registro Italiano LMC and Campus CML

Determinants of frontline tyrosine kinase inhibitor choice for patients with chronic‐phase chronic myeloid leukemia: A study from the Registro Italiano LMC and Campus CML

Efficacy and safety of nilotinib as frontline treatment in elderly (> 65 years) chronic myeloid leukemia patients outside clinical trials

Clinical updates on tyrosine kinase inhibitors in HER2-positive breast cancer

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