Reference Detail

Ref Type Journal Article
PMID (26847662)
Authors Douxfils J, Haguet H, Mullier F, Chatelain C, Graux C, Dogné JM
Title Association Between BCR-ABL Tyrosine Kinase Inhibitors for Chronic Myeloid Leukemia and Cardiovascular Events, Major Molecular Response, and Overall Survival: A Systematic Review and Meta-analysis.
Journal JAMA oncology
Vol
Issue
Date 2016 Feb 04
URL
Abstract Text A phase 3 trial with ponatinib in patients with chronic myeloid leukemia (CML) was interrupted due to an important increase of vascular occlusive events. A similar risk was also suspected with nilotinib, another BCR-ABL tyrosine kinase inhibitor (TKI) used in patients with CML.To assess the risk of vascular occlusive events in patients with CML treated by new generations of TKIs and provide an overall assessment of the clinical benefit.Two independent reviewers selected studies from PubMed, Scopus, and the Cochrane library database from their inception to October 21, 2014. Abstracts published during the past 3 years at international congresses and a trial register were also searched.Two independent reviewers screened abstracts and titles against inclusion and exclusion criteria published previously in the PROSPERO 2014 protocol: CRD42014014147. Among the 249 abstracts identified, 10 studies fulfilled the established criteria.Two investigators independently extracted data using a standard form.Information extracted included study and patients characteristics, type of intervention and data on vascular occlusive events, overall survival, and major molecular response (MMR). The meta-analysis was performed using a fixed-effects model. Odds ratios (ORs) with 95% CIs were computed using the Peto method.Ten randomized clinical trials (3043 patients) were analyzed. Risk of vascular occlusive events was increased with dasatinib (OR, 3.86; 95% CI, 1.33-11.18), nilotinib (OR, 3.42; 95% CI, 2.07-5.63), and ponatinib (OR, 3.47; 95% CI, 1.23-9.78) compared with imatinib in patients with CML. No significant difference was found with bosutinib (OR, 2.77; 95% CI, 0.39-19.77). New-generation TKIs increased the rate of MMR at 1 year compared with imatinib (overall OR, 2.22; 95% CI, 1.87 to 2.63). No statistical difference in overall survival at 1 year was found (overall OR, 1.20; 95% CI, 0.63-2.29). Inaccessibility to individual data and time-to-event data and differences in evaluation criteria between studies could have introduced bias.Dasatinib, nilotinib, and ponatinib increase vascular occlusive events. New-generation TKIs improve MMR but not the overall survival at 1 year in patients with CML.

Filtering

  • Case insensitive filtering will display rows where any text in any cell matches the filter term
  • Simple literal full or partial string matches
  • Separate multiple filter terms with a spaces, order doesn't matter (a b c and c b a are equivalent )
  • Filtering will only apply to rows that are already loaded on the page, filtering has no impact on query parameters
  • Use quotes to match a longer phrase which contains spaces "mtor c1483f"

Sorting

  • Generally, the default sort order for tables is set to be first column ascending, however, specific tables may set a different default sort order.
  • Click on any column header arrows to sort by that column
  • Hold down the Shift key and click multiple columns to sort by more than one column, be sure to set ascending or descending order for a given column, before moving on to the next column.

Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Therapy Description
Drug Name Trade Name Synonyms Drug Classes Drug Description
Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
Unknown unknown chronic myeloid leukemia not applicable Dasatinib Clinical Study Actionable In a meta-analysis, Sprycel (dasatinib) treatment was associated with increased rate of major molecular response compared with Gleevec (imatinib) (Odds Ratio (OR): 2.17 [1.66-2.83]), but not improved overall survival (OR: 0.42 [0.14-1.31]), and was associated with increased risk of vascular occlusive events (OR: 3.86 [1.33-11.18]) in patients with chronic myeloid leukemia (PMID: 26847662). 26847662
Unknown unknown chronic myeloid leukemia not applicable Nilotinib Clinical Study Actionable In a meta-analysis, Tasigna (nilotinib) treatment was associated with increased rate of major molecular response compared with Gleevec (imatinib) (Odds Ratio (OR): 2.45 [1.85-3.24]), but not improved overall survival (OR: 1.51 [0.38-5.99]), and was associated with increased risk of vascular occlusive events (OR: 3.42 [2.07-5.63]) in patients with chronic myeloid leukemia (PMID: 26847662). 26847662
Unknown unknown chronic myeloid leukemia not applicable Nilotinib FDA approved Actionable In a Phase III trial that supported FDA approval, treatment with Tasigna (nilotinib) resulted in improved hematologic response and overall survival rates compared to treatment with Gleevec (imatinib) in patients with Philadelphia chromosome positive chronic myeloid leukemia (PMID: 21091142). 21091142
Unknown unknown chronic myeloid leukemia not applicable Bosutinib Clinical Study Actionable In a meta-analysis, Bosulif (bosutinib) treatment was associated with increased rate of major molecular response compared with Gleevec (imatinib) (Odds Ratio (OR): 1.86 [1.29-2.70]), but not improved overall survival (OR: 2.38 [0.82-6.89]), and was associated with a trend toward increased risk of vascular occlusive events in chronic myeloid leukemia patients (PMID: 26847662). 26847662
Unknown unknown chronic myeloid leukemia not applicable Ponatinib Clinical Study Actionable In a meta-analysis, Iclusig (ponatinib) treatment was associated with increased rate of major molecular response compared with Gleevec (imatinib) (Odds Ratio (OR): 4.95 [0.97-25.19]), but not improved overall survival (OR: 2.00 [0.21-19.33]), and was associated with increased risk of vascular occlusive events (OR: 3.47 [1.23-9.78]) in patients with chronic myeloid leukemia (PMID: 26847662). 26847662
Unknown unknown chronic myeloid leukemia not applicable Ponatinib FDA approved Actionable In a Phase II clinical trial which supported FDA approval, Iclusig (ponatinib) was effective in promoting disease regression in 52% of patients with accelerated phase chronic myeloid leukemia, 31% of patients with blast phase chronic myeloid leukemia, and 41% of patients with Philadelphia chromosome positive acute lymphoblastic leukemia (PMID: 23935038). detail... 23935038