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Health Technology Assessment... 2012Nilotinib and dasatinib are now being considered as alternative treatments to imatinib as a first-line treatment of chronic myeloid leukaemia (CML). (Review)
Review
BACKGROUND
Nilotinib and dasatinib are now being considered as alternative treatments to imatinib as a first-line treatment of chronic myeloid leukaemia (CML).
OBJECTIVE
This technology assessment reviews the available evidence for the clinical effectiveness and cost-effectiveness of dasatinib, nilotinib and standard-dose imatinib for the first-line treatment of Philadelphia chromosome-positive CML.
DATA SOURCES
Databases [including MEDLINE (Ovid), EMBASE, Current Controlled Trials, ClinicalTrials.gov, the US Food and Drug Administration website and the European Medicines Agency website] were searched from search end date of the last technology appraisal report on this topic in October 2002 to September 2011.
REVIEW METHODS
A systematic review of clinical effectiveness and cost-effectiveness studies; a review of surrogate relationships with survival; a review and critique of manufacturer submissions; and a model-based economic analysis.
RESULTS
Two clinical trials (dasatinib vs imatinib and nilotinib vs imatinib) were included in the effectiveness review. Survival was not significantly different for dasatinib or nilotinib compared with imatinib with the 24-month follow-up data available. The rates of complete cytogenetic response (CCyR) and major molecular response (MMR) were higher for patients receiving dasatinib than for those with imatinib for 12 months' follow-up (CCyR 83% vs 72%, p < 0.001; MMR 46% vs 28%, p < 0.0001). The rates of CCyR and MMR were higher for patients receiving nilotinib than for those receiving imatinib for 12 months' follow-up (CCyR 80% vs 65%, p < 0.001; MMR 44% vs 22%, p < 0.0001). An indirect comparison analysis showed no difference between dasatinib and nilotinib for CCyR or MMR rates for 12 months' follow-up (CCyR, odds ratio 1.09, 95% CI 0.61 to 1.92; MMR, odds ratio 1.28, 95% CI 0.77 to 2.16). There is observational association evidence from imatinib studies supporting the use of CCyR and MMR at 12 months as surrogates for overall all-cause survival and progression-free survival in patients with CML in chronic phase. In the cost-effectiveness modelling scenario, analyses were provided to reflect the extensive structural uncertainty and different approaches to estimating OS. First-line dasatinib is predicted to provide very poor value for money compared with first-line imatinib, with deterministic incremental cost-effectiveness ratios (ICERs) of between £256,000 and £450,000 per quality-adjusted life-year (QALY). Conversely, first-line nilotinib provided favourable ICERs at the willingness-to-pay threshold of £20,000-30,000 per QALY.
LIMITATIONS
Immaturity of empirical trial data relative to life expectancy, forcing either reliance on surrogate relationships or cumulative survival/treatment duration assumptions.
CONCLUSIONS
From the two trials available, dasatinib and nilotinib have a statistically significant advantage compared with imatinib as measured by MMR or CCyR. Taking into account the treatment pathways for patients with CML, i.e. assuming the use of second-line nilotinib, first-line nilotinib appears to be more cost-effective than first-line imatinib. Dasatinib was not cost-effective if decision thresholds of £20,000 per QALY or £30,000 per QALY were used, compared with imatinib and nilotinib. Uncertainty in the cost-effectiveness analysis would be substantially reduced with better and more UK-specific data on the incidence and cost of stem cell transplantation in patients with chronic CML.
FUNDING
The Health Technology Assessment Programme of the National Institute for Health Research.
Topics: Antineoplastic Agents; Benzamides; Cost-Benefit Analysis; Cytogenetic Analysis; Dasatinib; Disease-Free Survival; Dose-Response Relationship, Drug; Humans; Imatinib Mesylate; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Models, Economic; Piperazines; Protein Kinase Inhibitors; Pyrimidines; Quality-Adjusted Life Years; Risk Assessment; Thiazoles
PubMed: 23134589
DOI: 10.3310/hta16420 -
Anticancer Research Sep 2017The current study aimed to determine the prognostic significance of thrombocytosis in patients with colorectal cancer (CRC) by a meta-analysis of the literature. (Meta-Analysis)
Meta-Analysis Review
AIM
The current study aimed to determine the prognostic significance of thrombocytosis in patients with colorectal cancer (CRC) by a meta-analysis of the literature.
PATIENTS AND METHODS
The meta-analysis followed the 2009 guidelines of Preferred Reporting Items for Systematic Reviews and Meta-Analyses. A systematic literature review was conducted from PubMed and Web of Science for articles published up to May 15, 2015. Sixteen studies with a total of 5,619 patients met the inclusion criteria. Hazard ratios and 95% confidence intervals were retrieved from the original articles, calculated from the published Kaplan-Meier survival curves, or the corresponding authors were contacted for additional information. Heterogeneity was assessed using the I statistic and Chi-square tests. Publication bias was assessed by Begg's funnel plot, Egger's linear regression test and trim-and-fill method. Sensitivity analysis was performed to validate the reliability.
RESULTS
Thrombocytosis is associated with shorter overall, disease-free and cancer-specific survival. Overall survival is reduced in patients with thrombocytosis regardless of their clinical tumor stage, and ethnicity. Shortened disease-free survival is associated with elevated platelet count in the non-specific stage (I-IV), localized tumor (stage I-III), and in the Asian patient population. Thrombocytosis is further associated with reduced cancer-specific survival in the non-specific stage and in Asian patients. Finally, thrombocytosis is significantly related to female patients, colon tumor location, T3-4 stage, lymph node positivity, metastasis, undifferentiated histology and lymphatic involvement.
CONCLUSION
Thrombocytosis portends adverse prognosis in CRC, and may serve as a clinically useful marker to facilitate risk stratification and guide postoperative management.
Topics: Colorectal Neoplasms; Disease-Free Survival; Female; Humans; Male; Prognosis; Thrombocytosis
PubMed: 28870890
DOI: 10.21873/anticanres.11878 -
BMC Nephrology Feb 2017Optimising filter life and performance efficiency in continuous renal replacement therapy has been a focus of considerable recent research. Larger high quality studies... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Optimising filter life and performance efficiency in continuous renal replacement therapy has been a focus of considerable recent research. Larger high quality studies have predominantly focussed on optimal anticoagulation however CRRT is complex and filter life is also affected by vascular access, circuit and management factors. We performed a systematic search of the literature to identify and quantify the effect of vascular access, circuit and patient factors that affect filter life and presented the results as a meta-analysis.
METHODS
A systematic review and meta-analysis was performed by searching Pubmed (MEDLINE) and Ovid EMBASE libraries from inception to 29 February 2016 for all studies with a comparator or independent variable relating to CRRT circuits and reporting filter life. Included studies documented filter life in hours with a comparator other than anti-coagulation intervention. All studies comparing anticoagulation interventions were searched for regression or hazard models pertaining to other sources of variation in filter life.
RESULTS
Eight hundred nineteen abstracts were identified of which 364 were selected for full text analysis. 24 presented data on patient modifiers of circuit life, 14 on vascular access modifiers and 34 on circuit related factors. Risk of bias was high and findings are hypothesis generating. Ranking of vascular access site by filter longevity favours: tunnelled semi-permanent catheters, femoral, internal jugular and subclavian last. There is inconsistency in the difference reported between femoral and jugular catheters. Amongst published literature, modality of CRRT consistently favoured continuous veno-venous haemodiafiltration (CVVHD-F) with an associated 44% lower failure rate compared to CVVH. There was a trend favouring higher blood flow rates. There is insufficient data to determine advantages of haemofilter membranes. Patient factors associated with a statistically significant worsening of filter life included mechanical ventilation, elevated SOFA or LOD score, elevations in ionized calcium, elevated platelet count, red cell transfusion, platelet factor 4 (PF-4) antibodies, and elevated fibrinogen. Majority of studies are observational or report circuit factors in sub-analysis. Risk of bias is high and findings require targeted investigations to confirm.
CONCLUSION
The interaction of patient, pathology, anticoagulation, vascular access, circuit and staff factors contribute to CRRT filter life. There remains an ambiguity from published data as to which site and side should be the first choice for vascular access placement and what interaction this has with patient factors and timing. Early consideration of tunnelled semi-permanent access may provide optimal filter life if longer periods of CRRT are anticipated. There remains an absence of robust evidence outside of anti-coagulation strategies despite over 20 years of therapy delivery however trends favour CVVHD-F over CVVH.
Topics: Autoantibodies; Calcium; Erythrocyte Transfusion; Fibrinogen; Hemodiafiltration; Humans; Kidney Failure, Chronic; Organ Dysfunction Scores; Platelet Factor 4; Renal Dialysis; Renal Replacement Therapy; Respiration, Artificial; Thrombocytosis; Time Factors
PubMed: 28219324
DOI: 10.1186/s12882-017-0445-5 -
Leukemia & Lymphoma Sep 2023Chronic myelomonocytic leukemia (CMML) is a myelodysplastic syndrome/myeloproliferative neoplasm (MDS/MPN) chacaterized by persistent peripheral blood monocytosis,...
Chronic myelomonocytic leukemia (CMML) is a myelodysplastic syndrome/myeloproliferative neoplasm (MDS/MPN) chacaterized by persistent peripheral blood monocytosis, hypercellular bone marrow and dysplasia at least in one myeloid lineage. CMML shares much of its molecular landscape with other myeloid neoplasms, while differs from others such as chronic neutrophilic leukemia (CNL), given the high frequency of CSF3R mutations in the latter. In this article, we report a case of CSF3R-mutated CMML and dissect this rare entity by reviewing the medical literature, with the intent to understand how this rare mutation shapes CMML's clinical and morphological phenotype. CSF3R-mutated CMML emerges as a rare entity meeting the ICC/WHO diagnostic criteria for CMML and simultaneously showing clinical-pathological and molecular traits of CNL and atypical chronic myeloid leukemia, rising an important and difficult diagnostic and therapeutical issue.
Topics: Humans; Leukemia, Myelomonocytic, Chronic; Leukemia, Neutrophilic, Chronic; Mutation; Myeloproliferative Disorders; Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative; Prognosis; Receptors, Colony-Stimulating Factor
PubMed: 37395413
DOI: 10.1080/10428194.2023.2227750 -
Hematology (Amsterdam, Netherlands) Dec 2021Infections in ruxolitinib-treated myeloproliferative neoplasm (MPN) patients were reported frequently. This work aimed to systematically estimate the risk of infection... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Infections in ruxolitinib-treated myeloproliferative neoplasm (MPN) patients were reported frequently. This work aimed to systematically estimate the risk of infection associated with ruxolitinib in MPN patients.
METHODS
The PUBMED, CNKI, EMBASE, Cochrane and CBM databases were searched to identify all related studies. Odds ratio (OR) and 95% confidence interval (CI) were used to express the difference between groups. was calculated to evaluate heterogeneity. Revman software was used to conduct the analysis.
RESULTS
Eleven randomized control trials were included in this analysis. The risk of overall infections was not different at the early stage of ruxolitinib use (OR, 95%CI: 1.23, [0.91, 1.67]). In the extension phase, overall infection was significantly lower in patients receiving ruxolitinib (OR, 95%CI: 0.53, [0.36, 0.79]). Herpes zoster infection was at higher risk both at early stage and in the extension phase (OR, 95%CI: 7.39, [1.33, 41.07]), (OR, 95%CI: 5.23, [1.46, 18.79]), respectively.
CONCLUSION
Our study suggested that ruxolitinib increased the risk of herpes zoster infection. However, current studies were not enough to estimate the effects of ruxolitinib on the risk of overall infection in patients with myeloproliferative neoplasm.
Topics: Female; Hematologic Neoplasms; Herpes Zoster; Humans; Male; Myeloproliferative Disorders; Nitriles; Pyrazoles; Pyrimidines; Randomized Controlled Trials as Topic
PubMed: 34493151
DOI: 10.1080/16078454.2021.1967256 -
Cytometry. Part B, Clinical Cytometry May 2021
Topics: Aged, 80 and over; CD4 Antigens; CD56 Antigen; Dendritic Cells; Flow Cytometry; Humans; Leukemia, Myelomonocytic, Chronic; Male; Myeloproliferative Disorders; Skin Neoplasms
PubMed: 32830878
DOI: 10.1002/cyto.b.21932 -
Expert Opinion on Drug Safety Jan 2024Ponatinib was recommended with caution because of its high risk of causing arterial occlusion events in chronic myeloid leukemia (CML) patients. The purpose of this... (Meta-Analysis)
Meta-Analysis Review
Comparative efficacy and safety of different doses of ponatinib versus other tyrosine kinase inhibitors for the treatment of chronic myeloid leukemia: a systematic review and network meta-analysis.
OBJECTIVE
Ponatinib was recommended with caution because of its high risk of causing arterial occlusion events in chronic myeloid leukemia (CML) patients. The purpose of this study was to understand the efficacy and safety of different doses of ponatinib in the treatment of CML, and to compare it with other tyrosine kinase inhibitors (TKIs).
METHOD
A network meta-analysis (NMA) was conducted by searching randomized controlled trials (RCTs) of ponatinib in patients with CML to compare the efficacy and safety of ponatinib, and ranked under the cumulative ranking curve (SUCRA) to evaluate the optimal treatment.
RESULTS
A total of seven articles with eight RCTs were included in this study, involving 45 mg, 30 mg and 15 mg ponatinib doses. Seven outcome indexes were analyzed. The results showed that 45 mg ponatinib was superior to other doses of ponatinib and other TKIs in CCyR, MCyR and CHR, but the incidence of SAEs and AOEs was significantly higher than other treatment regimens.
CONCLUSION
Ponatinib, with an initial dosage of 45 mg and a gradual reduction to 15 mg, may be a more favorable option for patients with CML at all stages of disease progression, rather than just those in the chronic phase of CML.
Topics: Humans; Tyrosine Kinase Inhibitors; Network Meta-Analysis; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Chronic Disease; Pyridazines; Protein Kinase Inhibitors; Antineoplastic Agents; Imidazoles
PubMed: 37852954
DOI: 10.1080/14740338.2023.2273339 -
Oncotarget Apr 2017Previous studies reported inconsistent findings about the relationship between pretreatment thrombocytosis and survival in patients with cervical cancer. This study... (Meta-Analysis)
Meta-Analysis Review
Previous studies reported inconsistent findings about the relationship between pretreatment thrombocytosis and survival in patients with cervical cancer. This study aimed to evaluate the prognostic significance of thrombocytosis in cervical cancer. We searched databases to identify relevant articles. Pooled hazard ratios (HRs), odds ratios (ORs), and 95% confidence intervals (CIs) were calculated. Fourteen studies including 3,394 patients were eligible for the meta-analysis. Overall, an elevated platelet count was significantly associated with inferior overall survival (OS, hazard ratio [HR]: 1.66, 95% confidence interval [CI]: 1.42-1.95, P < 0.001) and recurrence-free survival (RFS, HR: 1.67, 95% CI: 1.15-2.42, P = 0.007) but not progression-free survival (PFS, HR: 1.21, 95% CI: 0.89-1.64; P = 0.235). The results were similar for low stage patients treated with surgery alone. Moreover, a pretreatment thrombocytosis status was significantly associated with higher clinical stage (odd ratio [OR]: 2.39, 95% CI: 1.68-3.38, P < 0.001), positive pelvic node status (OR: 1.58, 95% CI: 1.01- 2.45, P = 0.044) and larger tumor size (OR: 2.32, 95% CI: 1.39-3.87, P = 0.001). Pretreatment thrombocytosis is an independent prognosis predictor in cervical cancer patients. It may be used as a readily available biomarker to refine clinical outcome prediction for cervical cancer patients.
Topics: Adult; Aged; Aged, 80 and over; Female; Humans; Middle Aged; Prognosis; Thrombocytosis; Uterine Cervical Neoplasms; Young Adult
PubMed: 28212582
DOI: 10.18632/oncotarget.15358 -
Acta Oncologica (Stockholm, Sweden) 2016The choice of a specific tyrosine kinase inhibitor (TKI) as first line treatment in chronic myeloid leukemia (CML) is complex and influenced by multiple factors. We... (Meta-Analysis)
Meta-Analysis Review
First line treatment with newer tyrosine kinase inhibitors in chronic myeloid leukemia associated with deep and durable molecular response - systematic review and meta-analysis.
BACKGROUND
The choice of a specific tyrosine kinase inhibitor (TKI) as first line treatment in chronic myeloid leukemia (CML) is complex and influenced by multiple factors. We published a meta-analysis examining the role of newer TKIs as first line treatment in chronic phase CML. In view of the recently published data, we decided to update it.
METHODS
We conducted a systematic review and meta-analysis of randomized controlled trials comparing first line treatment with imatinib to the newer TKIs (nilotinib, dasatinib, bosutinib and ponatinib). We searched MEDLINE, conference proceedings and databases of ongoing trials up to August 2015.
RESULTS
Our search yielded eight trials including 3554 patients. Treatment with the newer TKIs significantly improved major molecular response (MMR) at all time points and increased the rate of complete molecular response (CMR) at 12 and 24 months [relative risk (RR) 2.58, 95% CI 1.98-3.37, six trials and RR 2.05, 95% CI 1.63-2.58, three trials, respectively]. Early molecular response at three months was better with the newer TKIs (RR 1.33, 95% CI 1.26-1.40, six trials). Importantly, progression rate to accelerated or blastic phase was significantly lower with the newer TKIs at 12, 24 months and 5 years. Yet, there was no difference in all-cause mortality. The risk of adverse events requiring treatment discontinuation increased with the newer TKIs.
CONCLUSIONS
With a longer follow-up, the newer TKIs remain more potent than imatinib, yet with no significant effect on survival. As CMR is a prerequisite for treatment discontinuation and cure, the newer TKIs favor treatment cessation.
Topics: Antineoplastic Agents; Dasatinib; Disease Progression; Humans; Imatinib Mesylate; Imidazoles; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Protein Kinase Inhibitors; Pyridazines; Pyrimidines; Randomized Controlled Trials as Topic; Withholding Treatment
PubMed: 27560448
DOI: 10.1080/0284186X.2016.1201214 -
Biomarkers in Medicine Feb 2017Recently, several studies have reported that thrombocytosis may be associated with the poor prognosis of colorectal cancer (CRC). Nevertheless, their conclusions were... (Meta-Analysis)
Meta-Analysis Review
AIM
Recently, several studies have reported that thrombocytosis may be associated with the poor prognosis of colorectal cancer (CRC). Nevertheless, their conclusions were still controversial. Results & methodology: We searched PubMed, Embase, Cochrane Library and Web of Science up to April 2016. A total of 30 studies including 9129 patients were included in this meta-analysis. Thrombocytosis had a close relationship with the poor overall survival of CRC compared with normal platelet counts, with the pooled hazard ratios being 1.89 (95% CI: 1.45-2.47; p < 0.00001) and 1.83 (95% CI: 1.33-2.53; p = 0.0002), with univariate and multivariate analyses, respectively.
DISCUSSION & CONCLUSION
This meta-analysis indicated that thrombocytosis may be a cost-effective and noninvasive indicator for poor prognosis of patients with CRC, especially for overall survival.
Topics: Colorectal Neoplasms; Databases, Factual; Disease-Free Survival; Humans; Multivariate Analysis; Odds Ratio; Platelet Count; Prognosis; Proportional Hazards Models; Risk Factors; Survival Rate; Thrombocytosis
PubMed: 28097884
DOI: 10.2217/bmm-2016-0214