***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: BACKGROUND The efficacy of ceritinib in patients with untreated anaplastic lymphoma kinase (ALK)-rearranged non-small-cell lung cancer ( NSCLC ) is not known . We assessed the efficacy and safety of ceritinib versus platinum-based chemotherapy in these patients . METHODS This r and omised , open-label , phase 3 study in untreated patients with stage IIIB/IV ALK-rearranged non-squamous NSCLC was done in 134 centres across 28 countries . Eligible patients were assigned via interactive response technology to oral ceritinib 750 mg/day or platinum-based chemotherapy ( [ cisplatin 75 mg/m2 or carboplatin AUC 5 - 6 plus pemetrexed 500 mg/m2 ] every 3 weeks for four cycles followed by maintenance pemetrexed ) ; r and omisation was stratified by World Health Organization performance status ( 0 vs 1 - 2 ) , previous neoadjuvant or adjuvant chemotherapy , and presence of brain metastases as per investigator 's assessment at screening . Investigators and patients were not masked to treatment assignment . The primary endpoint was blinded independent review committee assessed progression-free survival , based on all r and omly assigned patients ( the full analysis set ) . Efficacy analyses were done based on the full analysis set . All safety analyses were done based on the safety set , which included all patients who received at least one dose of study drug . This trial is registered with Clinical Trials.gov , number NCT01828099 . FINDINGS Between Aug 19 , 2013 , and May 11 , 2015 , 376 patients were r and omly assigned to ceritinib ( n=189 ) or chemotherapy ( n=187 ) . Median progression-free survival ( as assessed by blinded independent review committee ) was 16·6 months ( 95 % CI 12·6 - 27·2 ) in the ceritinib group and 8·1 months ( 5·8 - 11·1 ) in the chemotherapy group ( hazard ratio 0·55 [ 95 % CI 0·42 - 0·73 ] ; p<0·00001 ) . The most common adverse events were diarrhoea ( in 160 [ 85 % ] of 189 patients ) , nausea ( 130 [ 69 % ] ) , vomiting ( 125 [ 66 % ] ) , and an increase in alanine aminotransferase ( 114 [ 60 % ] ) in the ceritinib group and nausea ( in 97 [ 55 % ] of 175 patients ) , vomiting ( 63 [ 36 % ] ) , and anaemia ( 62 [ 35 % ] ) in the chemotherapy group . INTERPRETATION First-line ceritinib showed a statistically significant and clinical ly meaningful improvement in progression-free survival versus chemotherapy in patients with advanced ALK-rearranged NSCLC . FUNDING Novartis Pharmaceuticals Corporation PURPOSE The purpose of this study was to determine whether the addition of the epidermal growth factor receptor tyrosine kinase inhibitor gefitinib ( Iressa , ZD1839 ; AstraZeneca , Wilmington , DE ) to st and ard first-line gemcitabine and cisplatin provides clinical benefit over gemcitabine and cisplatin alone in patients with advanced or metastatic non-small-cell lung cancer ( NSCLC ) .  Gefitinib has demonstrated encouraging efficacy in advanced NSCLC in phase II trials in pretreated patients , and a phase I trial of gefitinib in combination with gemcitabine and cisplatin showed favorable tolerability . PATIENTS AND METHODS This was a phase III r and omized , double-blind , placebo-controlled , multicenter trial in chemotherapy-naive patients with unresectable stage III or IV NSCLC . All patients received up to six cycles of chemotherapy ( cisplatin 80 mg/m(2 ) on day 1 and gemcitabine 1,250 mg/m(2 ) on days 1 and 8 of the 3-week cycle ) plus either gefitinib 500 mg/d , gefitinib 250 mg/d , or placebo . Daily gefitinib or placebo was continued until disease progression . End points included overall survival ( primary ) , time to progression , response rates , and safety evaluation . RESULTS A total of 1,093 patients were enrolled . There was no difference in efficacy end points between the treatment groups : for the gefitinib 500 mg/d , gefitinib 250 mg/d , and placebo groups , respectively , median survival times were 9.9 , 9.9 , and 10.9 months ( global ordered log-rank [ GOLrank ] P = .4560 ) , median times to progression were 5.5 , 5.8 , and 6.0 months ( GOLrank ; P = .7633 ) , and response rates were 49.7 % , 50.3 % , and 44.8 % . No significant unexpected adverse events were seen . CONCLUSION Gefitinib in combination with gemcitabine and cisplatin in chemotherapy-naive patients with advanced NSCLC did not have improved efficacy over gemcitabine and cisplatin alone . The reasons for this remain obscure and require further pre clinical testing BACKGROUND The efficacy of the ALK inhibitor crizotinib as compared with st and ard chemotherapy as first-line treatment for advanced ALK-positive non-small-cell lung cancer ( NSCLC ) is unknown . METHODS We conducted an open-label , phase 3 trial comparing crizotinib with chemotherapy in 343 patients with advanced ALK-positive nonsquamous NSCLC who had received no previous systemic treatment for advanced disease . Patients were r and omly assigned to receive oral crizotinib at a dose of 250 mg twice daily or to receive intravenous chemotherapy ( pemetrexed , 500 mg per square meter of body-surface area , plus either cisplatin , 75 mg per square meter , or carboplatin , target area under the curve of 5 to 6 mg per milliliter per minute ) every 3 weeks for up to six cycles . Crossover to crizotinib treatment after disease progression was permitted for patients receiving chemotherapy . The primary end point was progression-free survival as assessed by independent radiologic review . RESULTS Progression-free survival was significantly longer with crizotinib than with chemotherapy ( median , 10.9 months vs. 7.0 months ; hazard ratio for progression or death with crizotinib , 0.45 ; 95 % confidence interval [ CI ] , 0.35 to 0.60 ; P<0.001 ) . Objective response rates were 74 % and 45 % , respectively ( P<0.001 ) . Median overall survival was not reached in either group ( hazard ratio for death with crizotinib , 0.82 ; 95 % CI , 0.54 to 1.26 ; P=0.36 ) ; the probability of 1-year survival was 84 % with crizotinib and 79 % with chemotherapy . The most common adverse events with crizotinib were vision disorders , diarrhea , nausea , and edema , and the most common events with chemotherapy were nausea , fatigue , vomiting , and decreased appetite . As compared with chemotherapy , crizotinib was associated with greater reduction in lung cancer symptoms and greater improvement in quality of life . CONCLUSIONS Crizotinib was superior to st and ard first-line pemetrexed-plus-platinum chemotherapy in patients with previously untreated advanced ALK-positive NSCLC . ( Funded by Pfizer ; PROFILE 1014 Clinical Trials.gov number , NCT01154140 . ) BACKGROUND In single-group studies , chromosomal rearrangements of the anaplastic lymphoma kinase gene ( ALK ) have been associated with marked clinical responses to crizotinib , an oral tyrosine kinase inhibitor targeting ALK . Whether crizotinib is superior to st and ard chemotherapy with respect to efficacy is unknown . METHODS We conducted a phase 3 , open-label trial comparing crizotinib with chemotherapy in 347 patients with locally advanced or metastatic ALK-positive lung cancer who had received one prior platinum-based regimen . Patients were r and omly assigned to receive oral treatment with crizotinib ( 250 mg ) twice daily or intravenous chemotherapy with either pemetrexed ( 500 mg per square meter of body-surface area ) or docetaxel ( 75 mg per square meter ) every 3 weeks . Patients in the chemotherapy group who had disease progression were permitted to cross over to crizotinib as part of a separate study . The primary end point was progression-free survival . RESULTS The median progression-free survival was 7.7 months in the crizotinib group and 3.0 months in the chemotherapy group ( hazard ratio for progression or death with crizotinib , 0.49 ; 95 % confidence interval [ CI ] , 0.37 to 0.64 ; P<0.001 ) . The response rates were 65 % ( 95 % CI , 58 to 72 ) with crizotinib , as compared with 20 % ( 95 % CI , 14 to 26 ) with chemotherapy ( P<0.001 ) . An interim analysis of overall survival showed no significant improvement with crizotinib as compared with chemotherapy ( hazard ratio for death in the crizotinib group , 1.02 ; 95 % CI , 0.68 to 1.54 ; P=0.54 ) . Common adverse events associated with crizotinib were visual disorder , gastrointestinal side effects , and elevated liver aminotransferase levels , whereas common adverse events with chemotherapy were fatigue , alopecia , and dyspnea . Patients reported greater reductions in symptoms of lung cancer and greater improvement in global quality of life with crizotinib than with chemotherapy . CONCLUSIONS Crizotinib is superior to st and ard chemotherapy in patients with previously treated , advanced non-small-cell lung cancer with ALK rearrangement . ( Funded by Pfizer ; Clinical Trials.gov number , NCT00932893 . ) BACKGROUND Oncogenic fusion genes consisting of EML4 and anaplastic lymphoma kinase ( ALK ) are present in a subgroup of non-small-cell lung cancers , representing 2 to 7 % of such tumors . We explored the therapeutic efficacy of inhibiting ALK in such tumors in an early-phase clinical trial of crizotinib ( PF-02341066 ) , an orally available small-molecule inhibitor of the ALK tyrosine kinase . METHODS After screening tumor sample s from approximately 1500 patients with non-small-cell lung cancer for the presence of ALK rearrangements , we identified 82 patients with advanced ALK-positive disease who were eligible for the clinical trial . Most of the patients had received previous treatment . These patients were enrolled in an exp and ed cohort study instituted after phase 1 dose escalation had established a recommended crizotinib dose of 250 mg twice daily in 28-day cycles . Patients were assessed for adverse events and response to therapy . RESULTS Patients with ALK rearrangements tended to be younger than those without the rearrangements , and most of the patients had little or no exposure to tobacco and had adenocarcinomas . At a mean treatment duration of 6.4 months , the overall response rate was 57 % ( 47 of 82 patients , with 46 confirmed partial responses and 1 confirmed complete response ) ; 27 patients ( 33 % ) had stable disease . A total of 63 of 82 patients ( 77 % ) were continuing to receive crizotinib at the time of data cutoff , and the estimated probability of 6-month progression-free survival was 72 % , with no median for the study reached . The drug result ed in grade 1 or 2 ( mild ) gastrointestinal side effects . CONCLUSIONS The inhibition of ALK in lung tumors with the ALK rearrangement result ed in tumor shrinkage or stable disease in most patients . ( Funded by Pfizer and others ; Clinical Trials.gov number , NCT00585195 . ) PURPOSE Erlotinib is a potent reversible HER1/epidermal growth factor receptor ( EGFR ) tyrosine kinase inhibitor with single-agent activity in patients with non-small-cell lung cancer ( NSCLC ) .  Erlotinib was combined with chemotherapy to determine if it could improve the outcome of patients with NSCLC . PATIENTS AND METHODS TRIBUTE r and omly assigned patients with good performance status and previously untreated advanced ( stage IIIB/IV ) NSCLC to erlotinib 150 mg/d or placebo combined with up to six cycles of carboplatin and paclitaxel , followed by maintenance monotherapy with erlotinib . R and om assignment was stratified by stage , weight loss in the previous 6 months , measurable disease , and treatment center . The primary end point was overall survival ( OS ) . Secondary end points included time to progression ( TTP ) , objective response ( OR ) , and duration of response . RESULTS There were 1,059 assessable patients ( 526 erlotinib 
    Output:
    
The use of ALK-TKIs significantly increases the risk of developing high- grade ILD and QTc prolongation  in lung cancer patients .