***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 Gantenerumab is a fully human monoclonal antibody that binds aggregated amyloid-β ( Aβ ) and removes Aβ plaques by Fc receptor-mediated phagocytosis . In the SCarlet RoAD trial , we assessed the efficacy and safety of gantenerumab in prodromal Alzheimer ’s disease ( AD ) . Methods In this r and omized , double-blind , placebo-controlled phase III study , we investigated gantenerumab over 2 years . Patients were r and omized to gantenerumab 105 mg or 225 mg or placebo every 4 weeks by subcutaneous injection . The primary endpoint was the change from baseline to week 104 in Clinical Dementia Rating Sum of Boxes ( CDR-SB ) score . We evaluated treatment effects on cerebrospinal fluid biomarkers ( all patients ) and amyloid positron emission tomography ( sub study ) . A futility analysis was performed once 50 % of patients completed 2 years of treatment . Safety was assessed in patients who received at least one dose . Results Of the 3089 patients screened , 797 were r and omized . The study was halted early for futility ; dosing was discontinued ; and the study was unblinded . No differences between groups in the primary ( least squares mean [ 95 % CI ] CDR-SB change from baseline 1.60 [ 1.28 , 1.91 ] , 1.69 [ 1.37 , 2.01 ] , and 1.73 [ 1.42 , 2.04 ] for placebo , gantenerumab 105 mg , and gantenerumab 225 mg , respectively ) or secondary clinical endpoints were observed . The incidence of generally asymptomatic amyloid-related imaging abnormalities increased in a dose- and APOE ε4 genotype-dependent manner . Exploratory analyses suggested a dose-dependent drug effect on clinical and biomarker endpoints . Conclusions The study was stopped early for futility , but dose-dependent effects observed in exploratory analyses on select clinical and biomarker endpoints suggest that higher dosing with gantenerumab may be necessary to achieve clinical efficacy . Trial registration Clinical Trials.gov , NCT01224106 . Registered on October 14 , 2010 BACKGROUND Platinum-based doublet chemotherapy is recommended to treat advanced non-small-cell lung cancer ( NSCLC ) in fit , non-elderly adults , but monotherapy is recommended for patients older than 70 years . We compared a carboplatin and paclitaxel doublet chemotherapy regimen with monotherapy in elderly patients with advanced NSCLC . METHODS In this multicentre , open-label , phase 3 , r and omised trial we recruited patients aged 70 - 89 years with locally advanced or metastatic NSCLC and WHO performance status scores of 0 - 2 . Patients received either four cycles ( 3 weeks on treatment , 1 week off treatment ) of carboplatin ( on day 1 ) plus paclitaxel ( on days 1 , 8 , and 15 ) or five cycles ( 2 weeks on treatment , 1 week off treatment ) of vinorelbine or gemcitabine monotherapy . R and omisation was done central ly with the minimisation method . The primary endpoint was overall survival , and analysis was done by intention to treat . This trial is registered , number NCT00298415 . FINDINGS 451 patients were enrolled . 226 were r and omly assigned  monotherapy  and 225  doublet chemotherapy .  Median age was 77 years and median follow-up was 30.3 months ( range 8.6 - 45.2 ) . Median overall survival was 10.3 months for doublet chemotherapy and 6.2 months for monotherapy ( hazard ratio 0.64 , 95 % CI 0.52 - 0.78 ; p<0.0001 ) ; 1-year survival was 44.5 % ( 95 % CI 37.9 - 50.9 ) and 25.4 % ( 19.9 - 31.3 ) , respectively . Toxic effects were more frequent in the doublet chemotherapy group than in the monotherapy group ( most frequent , decreased neutrophil count ( 108 [ 48.4 % ] vs 28 [ 12.4 % ] ; asthenia 23 [ 10.3 % ] vs 13 [ 5.8 % ] ) . INTERPRETATION Despite increased toxic effects , platinum-based doublet chemotherapy was associated with survival benefits compared with vinorelbine or gemcitabine monotherapy in elderly patients with NSCLC . We feel that the current treatment paradigm for these patients should be reconsidered . FUNDING Intergroupe Francophone de Cancérologie Thoracique , Institut National du Cancer 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 advanced not selected NSCLC chemotherapy achieved an advantage of approximately 1 - 2 months on median survival versus best supportive care . Chemotherapy seems to improve symptoms control , even if r and omised studies with quality of life as first endpoint are lacking and often chemotherapy toxicity compromises the frail cost/benefit ratio . The aim of the present study is to evaluate the impact on QoL , substituting cisplatin , a pivot drug in NSCLC therapy , with carboplatin , an analogue with an improved toxicity profile . The combination of cisplatin with Mitomycin and Vinblastine was one of the most frequently used in the palliative setting at the time of design of our study . METHODS Patients were r and omized to receive MVP regimen ( Mitomycin-C 8 mg/m2 d1 , Vinblastine 4 mg/m2 d 1 - 8 , Cisplatin 100 mg/m2 d1 ) or MVC regimen ( Mitomycin-C 8 mg/m2 d1 , Vinblastine 4 mg/m2 d 1 - 8 , Carboplatin 300 mg/m2 d1 ) every 3 weeks . The QoL was evaluated by the Spitzer QL-Index and by the EORTC QLQ-C30+LC 13 question naires before chemotherapy , after one cycle , after three cycles , and then every 6 weeks in the first 6 months and every 3 months thenafter . RESULTS From September 1994 to July 1997 , 153 consecutive patients were r and omized to MVP ( 75 patients ) or MVC arm ( 78 patients ) . Despite difficulties in carrying out and analysing QoL items in such patients , the global QoL evaluated by the Spitzer 's question naire suggested an advantage for MVC regimen ( P=0.05 ) and a significant difference was observed in global health subdomain ( P=0.04 ) . The disease-related symptoms improved with time , and the benefits lasted for the entire treatment period . When evaluated with the EORTC question naire there was significantly less nausea and vomiting ( P=0.0001 ) , appetite loss ( P=0.01 ) , insomnia ( P=0.03 ) , constipation ( P=0.01 ) and peripheral neuropathy ( P=0.01 ) in favour of MVC , and a trend for less hair loss ( P=0.05 ) . The advantage lasted for all the duration of chemotherapy . No differences were observed in global quality of life subdomain ( P=0.40 ) between the two regimen . QoL was the first endpoint and the statistical power was inadequate to assess other parameters . However , we reported a response rate of 43.1 and 38.6 % , respectively , in MVP and MVC arm ( P=0.59 ) and a median survival of 10.2 and 7.2 months , respectively , for cisplatin and carboplatin arm ( P=0.39 ) . CONCLUSIONS The carboplatin containing regimen ( MVC ) has a significant better toxicity profile than the cisplatin containing ( MVP ) regimen as proven both by the EORTC question naires and by the WHO toxicity data reported by physicians . No significant differences in terms of response rate , time to progression and overall survival were observed between the two regimen . The two chemotherapy regimen showed a similar effectiveness in symptom palliation when evaluated with C30 addendum of EORTC QOL question naire . With the Spitzer 's question naires a trend towards an improved quality of life index was observed during treatment with the carboplatin combination in comparison to the cisplatin combination . This difference , however , was not observed when the global quality of life was evaluated with the EORTC patients compiled question naires . A carboplatin containing regimen with better toxicity profile and a similar potentiality for symptoms control offers an option in comparison to similar cisplatin containing combinations in the palliative treatment of advanced NSCLC BACKGROUND Erlotinib has been shown to improve progression-free survival compared with chemotherapy when given as first-line treatment for Asian patients with non-small-cell lung cancer ( NSCLC ) with activating EGFR mutations . We aim ed to assess the safety and efficacy of erlotinib compared with st and ard chemotherapy for first-line treatment of European patients with advanced EGFR-mutation positive NSCLC . METHODS We undertook the open-label , r and omised phase 3 EURTAC trial at 42 hospitals in France , Italy , and Spain . Eligible participants were adults ( > 18 years ) with NSCLC and EGFR mutations ( exon 19 deletion or L858R mutation in exon 21 ) with no history of chemotherapy for metastatic disease ( neoadjuvant or adjuvant chemotherapy ending ≥ 6 months before study entry was allowed ) . We r and omly allocated participants ( 1:1 ) according to a computer-generated allocation schedule to receive oral erlotinib 150 mg per day or 3 week cycles of st and ard intravenous chemotherapy of cisplatin 75 mg/m(2 ) on day 1 plus docetaxel ( 75 mg/m(2 ) on day 1 ) or gemcitabine ( 1250 mg/m(2 ) on days 1 and 8) . Carboplatin ( AUC 6 with docetaxel 75 mg/m(2 ) or AUC 5 with gemcitabine 1000 mg/m(2 ) ) was allowed in patients unable to have cisplatin . Patients were stratified by EGFR mutation type and Eastern Cooperative Oncology Group performance status ( 0 vs 1 vs 2 ) . The primary endpoint was progression-free survival ( PFS ) in the intention-to-treat population . We assessed safety in all patients who received study drug ( ≥ 1 dose ) . This study is registered with Clinical Trials.gov , number NCT00446225 . FINDINGS Between Feb 15 , 2007 , and Jan 4 , 2011 , 174 patients with EGFR mutations were enrolled . One patient received treatment before r and omisation and was thus withdrawn from the study ; of the remaining patients , 86 were r and omly assigned to receive erlotinib and 87 to receive st and ard chemotherapy . The preplanned interim analysis showed that the study met its primary endpoint 
    Output:
    
G3 - 4 hematological toxicities were also more frequent in this group .
This meta- analysis suggests that platinum-combination regimens are superior to singleagent both in terms of ORR and survival-rate with increase of severe hematological toxicities