***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Dasatinib is a highly potent BCR-ABL inhibitor with established efficacy and safety in imatinib-resistant/-intolerant patients with chronic myeloid leukemia ( CML ) . In the phase 3 DASISION trial , patients with newly diagnosed chronic-phase ( CP ) CML were r and omized to receive dasatinib 100 mg ( n = 259 ) or imatinib 400 mg ( n = 260 ) once daily . Primary data showed superior efficacy for dasatinib compared with imatinib after 12 months , including significantly higher rates of complete cytogenetic response ( CCyR ) , confirmed CCyR ( primary end point ) , and major molecular response ( MMR ) . Here , 24-month data are presented . Cumulative response rates by 24 months in dasatinib and imatinib arms were : CCyR in 86 % versus 82 % , MMR in 64 % versus 46 % , and BCR-ABL reduction to ≤ 0.0032 % ( 4.5-log reduction ) in 17 % versus 8 % . Transformation to accelerated-/ blast-phase CML on study occurred in 2.3 % with dasatinib versus 5.0 % with imatinib . BCR-ABL mutations , assessed after discontinuation , were detected in 10 patients in each arm . In safety analyses , fluid retention , superficial edema , myalgia , vomiting , and rash were less frequent with dasatinib compared with imatinib , whereas pleural effusion and grade 3/4 thrombocytopenia were more frequent with dasatinib . Overall , dasatinib continues to show faster and deeper responses compared with imatinib , supporting first-line use of dasatinib in patients with newly diagnosed CML-CP . This study was registered at Clinical Trials.gov : NCT00481247 6509 Background : The phase 3 BELA study compared BOS ( competitive dual Src/Abl kinase inhibitor ) with IM in newly diagnosed CP CML . METHODS 502 pts with CP CML stratified by Sokal score and region were r and omized to  oral BOS 500 mg/d ( n = 250 ) or IM 400 mg/d ( n = 252 ) . Study design and endpoints have been described ( Gambacorti , ASH 2010 ) . Efficacy analyses included all r and omized pts ( ITT ) ; safety analyses included all treated pts . RESULTS Median treatment duration was 16.6 mo for BOS and 16.8 mo for IM ; 69 % and 78 % of pts , respectively , were still receiving therapy . CCyR rates at 1 y were 70 % ( BOS ) and 68 % ( IM ) ; cumulative CCyR rates by 1 y were 79 % ( BOS ) and 75 % ( IM ) . MMR rates at 1 y were higher for BOS vs IM ( 39 % vs 26 % ; P = 0.002 ) , as were cumulative MMR rates by 1 y ( 47 % vs 32 % ; P < 0.001 ) . Time to CCyR and MMR were significantly shorter with BOS ( P < 0.001 for both ) . Transformation to accelerated/blast phase occurred in 4 ( 2 % ) pts on BOS and 10 ( 4 % ) pts on IM ( P = 0.053 ) . Common treatment-emergent adverse events ( TEAEs ; ≥20 % of pts ) observed with BOS and IM , respectively , were diarrhea ( 68 % , 22 % ) , vomiting ( 31 % , 14 % ) , nausea ( 31 % , 35 % ) , rash ( 21 % , 16 % ) and muscle cramps ( 4 % , 20 % ) . Pleural effusions were seen in 3 % of BOS pts ( no IM pts ) . Grade ≥3 TEAEs ( ≥2 % of pts ) seen with BOS were diarrhea ( 10 % ) , vomiting ( 3 % ) , pneumonia ( 3 % ) , and dyspnea ( 2 % ) . Median cumulative duration of diarrhea was 33 d for BOS and 17 d for IM . Grade ≥3 lab abnormalities ( ≥10 % of pts ) with BOS and IM , respectively , were elevated alanine aminotransferase ( 23 % , 3 % ) , thrombocytopenia ( 14 % , 14 % ) , elevated aspartate aminotransferase ( 11 % , 3 % ) , neutropenia ( 9 % , 21 % ) and hypophosphatemia ( 4 % , 17 % ) . 22 % of BOS pts and 6 % of IM pts discontinued due to AEs , none due to diarrhea . Deaths occurred in 4 ( 1.6 % ) BOS pts and 12 ( 4.8 % ) IM pts ; overall , 81 % died from disease progression . CONCLUSIONS Efficacy and safety were consistent with previously reported results . BOS showed a significantly higher MMR rate at 1 y , significantly faster times to CCyR and MMR , and lower transformation rate vs IM . BOS had a distinct and acceptable toxicity profile and may offer a new therapeutic option in newly diagnosed Ph+ CP CML . Data for 18-mo follow-up will be presented 6512 Background : Dasatinib , a potent BCR-ABL inhibitor , is indicated as a second-line therapy for patients ( pts ) with imatinib-resistant or -intolerant CML . This 5-year ( yr ) analysis is the longest follow-up of CML-CP pts treated with a second-generation BCR-ABL inhibitor .  METHODS Study design and endpoints have been described previously ( Shah 2008 , J Clin Oncol ) . Pts ( N=670 ) were r and omized to dasatinib  : 100 mg once daily ( QD ) , 50 mg twice daily ( BID ) , 140 mg QD , or 70 mg BID . RESULTS Results herein are based on 4-yr data ; 5-yr data will be presented . After 4 yrs minimum follow-up , 251 ( 37 % ) pts remain on treatment . More pts remain on treatment in the dasatinib 100 mg QD arm ( n=74 ) compared with all other arms . Efficacy data for pts r and omized to 100 mg QD ( n=167 ) are : 66 % progression-free survival ( PFS ) , 82 % overall survival ( OS ) , and 4 % transformation to advanced disease . In a l and mark analysis of dasatinib 100 mg QD , achievement of complete cytogenetic response ( CCyR with or without major molecular response ) at 12 months ( mos ) is associated with an 87 % PFS , and achievement of a partial CyR is associated with 78 % PFS compared with PFS of 45 % for pts with other/no CyR. For dasatinib 100 mg QD , non-hematologic adverse events ( AEs ; all grade s ) generally first occur < 24 mos and cumulatively include : headache ( 33 % ) , diarrhea ( 28 % ) , fatigue ( 25 % ) , and pleural effusion ( 24 % ) ; and hematologic AEs ( grade s 3/4 ) generally occur < 12 mos : neutropenia ( 36 % ) and thrombocytopenia ( 24 % ) . Dose/schedule modifications were permitted to manage AEs . Analysis of dosing by last dose available demonstrates that , across the 4 arms , 178 ( 71 % ) pts were on QD dosing , of which 107 ( 60 % ) pts were on ≥100 mg QD . Switching from BID to QD dosing occurred in 44 % of pts . CONCLUSIONS The majority of pts on treatment after 4 yrs continue on the QD dosing schedule . Long-term follow-up of dasatinib 100 mg QD further demonstrates durable efficacy and a generally better tolerated safety profile for pts with CML-CP following prior imatinib therapy Imatinib mesylate ( IM ) , 400 mg daily , is the st and ard treatment of Philadelphia-positive ( Ph(+ ) ) chronic myeloid leukemia ( CML ) . Pre clinical data and results of single-arm studies raised the suggestion that better results could be achieved with a higher dose . To investigate whether the systematic use of a higher dose of IM could lead to better results , 216 patients with Ph(+ ) CML at high risk ( HR ) according to the Sokal index were r and omly assigned to receive IM 800 mg or 400 mg daily , as front-line therapy , for at least 1 year . The CCgR rate at 1 year was 64 % and 58 % for the high-dose arm and for the st and ard-dose arm , respectively ( P = .435 ) . No differences were detectable in the CgR at 3 and 6 months , in the molecular response rate at any time , as well as in the rate of other events . Twenty-four ( 94 % ) of 25 patients who could tolerate the full 800-mg dose achieved a CCgR , and only 4 ( 23 % ) of 17 patients who could tolerate less than 350 mg achieved a CCgR. This study does not support the extensive use of high-dose IM ( 800 mg daily ) front-line in all CML HR patients . This trial was registered at www . clinical trials.gov as # NCT00514488 Although imatinib induces marked responses in patients with chronic myeloid leukemia ( CML ) , resistance is increasingly problematic , and treatment options for imatinib-resistant or -intolerant CML are limited . Dasatinib , a novel , highly potent , oral , multitargeted kinase inhibitor of BCR-ABL and SRC family kinases , induced cytogenetic responses in a phase 1 study in imatinib-resistant or -intolerant CML and was well tolerated . Initial results are presented from a phase 2 study of 186 patients with imatinib-resistant or -intolerant chronic-phase CML ( CML-CP ) design ed to further establish the efficacy and safety of dasatinib ( 70 mg twice daily ) . At 8-months ' follow-up , dasatinib induced notable responses , with 90 % and 52 % of patients achieving complete hematologic and major cytogenetic responses ( MCyR ) , respectively . Responses were long lasting : only 2 % of patients achieving MCyR progressed or died . Importantly , comparable responses were achieved by patients carrying BCR-ABL mutations conferring imatinib resistance .  Dasatinib also induced molecular responses , reducing BCR-ABL/ABL transcript ratios from 66 % at baseline to 2.6 % at 9 months . Nonhematologic adverse events were generally mild to moderate , and most cytopenias were effectively managed with dose modifications . Cross-intolerance with imatinib was not evident . To conclude , dasatinib induces notable responses in imatinib-resistant or -intolerant CML-CP , is well tolerated , and represents a promising therapeutic option for these patients . This trial was registered at www . clinical trials.gov as CA180013 Treatment options are limited for patients with imatinib-resistant or -intolerant accelerated phase chronic myeloid leukemia ( CML-AP ) .  Dasatinib is a novel , potent , oral , multitargeted kinase inhibitor of BCR-ABL and SRC-family kinases that showed marked efficacy in a phase 1 trial of patients with imatinib-resistant CML . Results are presented for 107 patients with CML-AP with imatinib-resistance or -intolerance from a phase 2 , open-label study further evaluating dasatinib  efficacy and safety . At 8 months ' minimum follow-up , 81 % , 64 % , and 39 % of patients achieved overall , major ( MaHR ) , and complete hematologic responses , respectively , whereas 33 % and 24 % attained major and complete cytogenetic remission . Of 69 patients who achieved MaHR , 7 progressed . Seventy-six percent of patients are estimated to be alive and progression-free at 10 months . Response rates for the 60 % of patients with baseline BCR-ABL mutations did not differ from the total population . Dasatinib was well tolerated : most nonhematologic adverse events ( AEs ) were mild to moderate ; no imatinib-intolerant patients discontinued dasatinib because of AEs . Although common ( 76 % of patients with severe neutropenia ) , cytopenias were manageable through dose modification . In summary , dasatinib induced significant hematologic and cytogenetic responses in patients with imatinib resistance or intolerance , was well tolerated , and may represent a potent new therapeutic option for CML-AP . Further follow-up is warranted . This trial was registered at www . clinical trials.gov as # CA180005 Responses can be achieved with dasatinib or nilotinib after failure of 2 prior tyrosine kinase inhibitors ( TKIs ) . We report on 48 chronic myeloid leukemia patients sequentially treated with 3 TKIs : 34 with dasatinib after imatinib/nilotinib failure and 14 with nilotinib after imatinib/dasatinib failure . Before the third TKI , 25 patients were in chronic phase ( CP ) , 10 in accelerated phase ( AP ) , and 1 
    Output:
    
Each of the second-generation TKIs was associated with a distinct adverse-event profile .
Data in the second- and third-line setting confirmed the efficacy of the second-generation TKIs in either imatinib-resistant or -intolerant patients , as measured by CCyR and MMR rates .
Data from first-line r and omized controlled trials reporting up to 2-year follow-up indicate superior response rates of the second-generation TKIs compared with imatinib .
Current evidence from single-arm studies in the second-line setting confirm that nilotinib , dasatinib , and bosutinib are valuable treatment options for the significant subgroup of patients who are intolerant or resistant to imatinib treatment