***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 Crizotinib confers improved progression-free survival compared with chemotherapy in anaplastic lymphoma kinase (ALK)-rearranged non-small-cell lung cancer ( NSCLC ) , but progression invariably occurs . We investigated the efficacy and safety of alectinib , a potent and selective ALK inhibitor with excellent CNS penetration , in patients with crizotinib-refractory ALK-positive NSCLC . PATIENTS AND METHODS Alectinib 600 mg was administered orally twice daily . The primary end point was objective response rate ( ORR ) by central independent review committee ( IRC ) . RESULTS Of the 138 patients treated , 84 patients ( 61 % ) had CNS metastases at baseline , and 122 were response evaluable ( RE ) by IRC .  ORR by IRC was 50 % ( 95 % CI , 41 % to 59 % ) , and the median duration of response ( DOR ) was 11.2 months ( 95 % CI , 9.6 months to not reached ) . In 96 patients ( 79 % ) previously treated with chemotherapy , the ORR was 45 % ( 95 % CI , 35 % to 55 % ) . Median IRC-assessed progression-free survival for all 138 patients was 8.9 months ( 95 % CI , 5.6 to 11.3 months ) . CNS disease control rate was 83 % ( 95 % CI , 74 % to 91 % ) , and the median CNS DOR was 10.3 months ( 95 % CI , 7.6 to 11.2 months ) . CNS ORR in 35 patients with baseline measurable CNS lesions was 57 % ( 95 % CI , 39 % to 74 % ) . Of the 23 patients with baseline CNS metastases ( measurable or nonmeasurable ) and no prior radiation , 10 ( 43 % ) had a complete CNS response . At 12 months , the cumulative CNS progression rate ( 24.8 % ) was lower than the cumulative non-CNS progression rate ( 33.2 % ) for all patients . Common adverse events were constipation ( 33 % ) , fatigue ( 26 % ) , and peripheral edema ( 25 % ) ; most were grade 1 to 2 . CONCLUSION Alectinib is highly active and well tolerated in patients with advanced , crizotinib-refractory ALK-positive NSCLC , including those with CNS metastases 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 . ) In this prospect i ve phase III trial , afatinib combined with paclitaxel improved progression-free survival and objective response , compared with single-agent chemotherapy , in patients with NSCLC who were clinical ly enriched for ErbB dependency having failed platinum-based chemotherapy , gefitinib/erlotinib and afatinib monotherapy after initial benefit on each tyrosine kinase inhibitor BACKGROUND Non-small-cell lung cancer with sensitive mutations of the epidermal growth factor receptor ( EGFR ) is highly responsive to EGFR tyrosine kinase inhibitors such as gefitinib , but little is known about how its efficacy and safety profile compares with that of st and ard chemotherapy . METHODS We r and omly assigned 230 patients with metastatic , non-small-cell lung cancer and EGFR mutations who had not previously received chemotherapy to receive gefitinib or carboplatin-paclitaxel .  The primary end point was progression-free survival ; secondary end points included overall survival , response rate , and toxic effects . RESULTS In the planned interim analysis of data for the first 200 patients , progression-free survival was significantly longer in the gefitinib group than in the st and ard-chemotherapy group ( hazard ratio for death or disease progression with gefitinib , 0.36 ; P<0.001 ) , result ing in early termination of the study . The gefitinib group had a significantly longer median progression-free survival ( 10.8 months , vs. 5.4 months in the chemotherapy group ; hazard ratio , 0.30 ; 95 % confidence interval , 0.22 to 0.41 ; P<0.001 ) , as well as a higher response rate ( 73.7 % vs. 30.7 % , P<0.001 ) . The median overall survival was 30.5 months in the gefitinib group and 23.6 months in the chemotherapy group ( P=0.31 ) . The most common adverse events in the gefitinib group were rash ( 71.1 % ) and elevated aminotransferase levels ( 55.3 % ) , and in the chemotherapy group , neutropenia ( 77.0 % ) , anemia ( 64.6 % ) , appetite loss ( 56.6 % ) , and sensory neuropathy ( 54.9 % ) . One patient receiving gefitinib  died from interstitial lung disease . CONCLUSIONS First-line gefitinib for patients with advanced non-small-cell lung cancer who were selected on the basis of EGFR mutations improved progression-free survival , with acceptable toxicity , as compared with st and ard chemotherapy . ( UMIN-CTR number , C000000376 . 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 
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Sub-group analysis according to ALK-TKIs showed that the incidence of liver toxicities associated with ceritinib was higher than that of crizotinib and alectinib .
Conclusions The use of ALK-TKIs significantly increases the risk of developing all- grade and high- grade liver toxicities  in lung cancer patients