human
***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 Several studies have shown the efficacy , tolerability , and ease of administration of pemetrexed-an antifolate antineoplastic agent-in  patients with advanced non-small-cell lung cancer . We assessed pemetrexed as maintenance therapy in patients with this disease . METHODS This r and omised double-blind study was undertaken in 83 centres in 20 countries . 663 patients with stage IIIB or IV disease who had not progressed on four cycles of platinum-based chemotherapy  were r and omly assigned ( 2:1 ratio ) to receive pemetrexed ( 500 mg/m(2 ) , day 1 ) plus best supportive care ( n=441 ) or placebo plus best supportive care ( n=222 ) in 21-day cycles until disease progression . Treatment was r and omised with the Simon and Pocock minimisation method . Patients and investigators were masked to treatment . All patients received vitamin B(12 ) , folic acid , and dexamethasone . The primary endpoint of progression-free survival and the secondary endpoint of overall survival were analysed by intention to treat . This study is registered with Clinical Trials.gov , number NCT00102804 . FINDINGS All r and omly assigned participants were analysed . Pemetrexed significantly improved progression-free survival ( 4.3 months [ 95 % CI 4.1 - 4.7 ] vs 2.6 months [ 1.7 - 2.8 ] ; hazard ratio [ HR ] 0.50 , 95 % CI 0.42 - 0.61 , p<0.0001 ) and overall survival ( 13.4 months [ 11.9 - 15.9 ] vs 10.6 months [ 8.7 - 12.0 ] ; HR 0.79 , 0.65 - 0.95 , p=0.012 ) compared with placebo . Treatment discontinuations due to drug-related toxic effects were higher in the pemetrexed group than in the placebo group ( 21 [ 5 % ] vs three [ 1 % ] ) . Drug-related grade three or higher toxic effects were higher with pemetrexed than with placebo ( 70 [ 16 % ] vs nine [ 4 % ] ; p<0.0001 ) , specifically fatigue ( 22 [ 5 % ] vs one [ 1 % ] , p=0.001 ) and neutropenia ( 13 [ 3 % ] vs 0 , p=0.006 ) . No  pemetrexed-related deaths occurred . Relatively fewer patients in the pemetrexed group than in the placebo group received systemic post-discontinuation therapy ( 227 [ 51 % ] vs 149 [ 67 % ] ; p=0.0001 ) . INTERPRETATION Maintenance therapy with pemetrexed is well tolerated and offers improved progression-free and overall survival compared with placebo in patients with advanced non-small-cell lung cancer . FUNDING Eli Lilly Background : Patient-level data from 2 phase III studies in patients with previously untreated , advanced-stage , nonsquamous non – small cell lung cancer ( NSCLC ) were pooled to examine outcomes with bevacizumab and chemotherapy based on age . Methods : Data from patients r and omized to paclitaxel – carboplatin (PC)+bevacizumab in the Eastern Cooperative Oncology Group 4599 ( E4599 ) and PointBreak studies were pooled and compared with E4599 patients r and omized to PC alone . Patients were grouped by age : below 65 , 65 to 74 , 70 to 74 , below 75 , and 75 years or above . A multivariable model was used to calculate hazard ratios ( HRs ) and corresponding 95 % confidence intervals ( CIs ) using time-to-event outcomes . Adverse events ( AEs ) were assessed by age group in each study . Results : The PC+bevacizumab and PC arms comprised 901 and 444 patients , respectively . PC+bevacizumab was associated with significant increases in overall survival relative to PC in patients below 65 years ( hazards ratio [ HR ] , 0.75 ; 95 % confidence interval [ CI ] , 0.62 - 0.89 ) , 65 to 74 years ( HR , 0.80 ; 95 % CI , 0.64 - 1.00 ) , 70 to 74 years ( HR , 0.68 ; 95 % CI , 0.48 - 0.96 ) , and below 75 years ( HR , 0.78 ; 95 % CI , 0.68 - 0.89 ) but not in those aged 75 years or above ( HR , 1.05 ; 95 % CI , 0.70 - 1.57 ) . Increased incidence of grade ≥3 AEs was reported with PC+bevacizumab versus PC in patients below 75 years ( 63 % vs. 48 % ; P<0.05 ) and 75 years or above ( 81 % vs. 56 % ; P < 0.05 ) in E4599 . Conclusions : This analysis suggests that the survival benefits  associated with PC+bevacizumab extend to patient subgroups below 75 years with advanced-stage NSCLC ; no benefit , however , was observed for bevacizumab-eligible patients who were 75 years or above BACKGROUND We conducted a r and omized , placebo-controlled , double-blind trial to determine whether the epidermal growth factor receptor inhibitor erlotinib prolongs survival in non-small-cell lung cancer after the failure of first-line or second-line chemotherapy . METHODS Patients with stage IIIB or IV non-small-cell lung cancer , with performance status from 0 to 3 , were eligible if they had received one or two prior chemotherapy regimens .  The patients were stratified according to center , performance status , response to prior chemotherapy , number of prior regimens , and prior platinum-based therapy and were r and omly assigned in a 2:1 ratio to receive oral erlotinib , at a dose of 150 mg daily , or placebo . RESULTS The median age of the 731 patients who underwent r and omization was 61.4 years ; 49 percent had received two prior chemotherapy regimens , and 93 percent had received platinum-based chemotherapy .  The response rate was 8.9 percent in the erlotinib group and less than 1 percent in the placebo group ( P<0.001 ) ; the median duration of the response was 7.9 months and 3.7 months , respectively . Progression-free survival was 2.2 months and 1.8 months , respectively ( hazard ratio , 0.61 , adjusted for stratification categories ; P<0.001 ) . Overall survival was 6.7 months and 4.7 months , respectively ( hazard ratio , 0.70 ; P<0.001 ) , in favor of erlotinib . Five percent of patients discontinued erlotinib because of toxic effects . CONCLUSIONS Erlotinib can prolong survival in patients with non-small-cell lung cancer after first-line or second-line chemotherapy This r and omised multicentre trial was conducted to establish the optimal duration of palliative chemotherapy in advanced non-small-cell lung cancer ( NSCLC ) . We compared a policy of three vs six courses of new-generation platinum-based combination chemotherapy with regard to effects on quality of life ( QoL ) and survival .  Patients with stage IIIB or IV NSCLC and WHO performance status ( PS ) 0–2 were r and omised to receive three ( C3 ) or six ( C6 ) courses of carboplatin ( area under the curve ( AUC ) 4 , Chatelut 's formula , equivalent to Calvert 's AUC 5 ) on day 1 and vinorelbine 25 mg m−2 on days 1 and 8 of a 3-week cycle . Key end points were QoL at 18 weeks , measured with EORTC Quality of Life Question naire (QLQ)-C30 and QLQ-LC13 , and overall survival . Secondary end points were progression-free survival and need of palliative radiotherapy . Two hundred and ninety-seven patients were r and omised ( C3 150 , C6 147 ) . Their median age was 65 years , 30 % had PS 2 and 76 % stage IV disease . Seventy-eight and 54 % of C3 and C6 patients , respectively , completed all scheduled chemotherapy courses . Compliance with QoL question naires was 88 % . There were no significant group differences in global QoL , pain or fatigue up to 26 weeks . The dyspnoea palliation rate was lower in the C3 arm at 18 and 26 weeks ( P<0.05 ) , but this finding was inconsistent across different methods of analysis . Median survival in the C3 group was 28 vs 32 weeks in the C6 group ( P=0.75 , HR 1.04 , 95 % CI 0.82–1.31 ) . One- and 2-year survival rates were 25 and 9 % vs 25 and 5 % in the C3 and C6 arm , respectively . Median progression-free survival was 16 and 21 weeks in the C3 and C6 groups , respectively ( P=0.21 , HR 0.86 , 95 % CI 0.68–1.08 ) . In conclusion , palliative chemotherapy with carboplatin and vinorelbine beyond three courses conveys no survival or consistent QoL benefits in advanced NSCLC BACKGROUND The irreversible ErbB family blocker afatinib and the reversible EGFR tyrosine kinase inhibitor gefitinib are approved for first-line treatment of EGFR mutation-positive non-small-cell lung cancer ( NSCLC ) . We aim ed to compare the efficacy and safety of afatinib and gefitinib in this setting . METHODS This multicentre , international , open-label , exploratory , r and omised controlled phase 2B trial ( LUX-Lung 7 ) was done at 64 centres in 13 countries . Treatment-naive patients with stage IIIB or IV NSCLC and a common EGFR mutation ( exon 19 deletion or Leu858Arg ) were r and omly assigned ( 1:1 ) to receive afatinib ( 40 mg per day ) or gefitinib ( 250 mg per day ) until disease progression , or beyond if deemed beneficial by the investigator . R and omisation , stratified by EGFR mutation type and status of brain metastases , was done central ly using a vali date d number generating system implemented via an interactive voice or web-based response system with a block size of four . Clinicians and patients were not masked to treatment allocation ; independent review of tumour response was done in a blinded manner . Co primary endpoints were progression-free survival by independent central review , time-to-treatment failure , and overall survival . Efficacy analyses were done in the intention-to-treat population and safety analyses were done in patients who received at least one dose of study drug . This ongoing study is registered with Clinical Trials.gov , number NCT01466660 . FINDINGS Between Dec 13 , 2011 , and Aug 8 , 2013 , 319 patients were r and omly assigned ( 160 to afatinib and 159 to gefitinib ) . Median follow-up was 27·3 months ( IQR 15·3 - 33·9 ) . Progression-free survival ( median 11·0 months [ 95 % CI 10·6 - 12·9 ] with afatinib vs 10·9 months [ 9·1 - 11·5 ] with gefitinib ; hazard ratio [ HR ] 0·73 [ 95 % CI 0·57 - 0·95 ] , p=0·017 ) and time-to-treatment failure ( median 13·7 months [ 95 % CI 11·9 - 15·0 ] with afatinib vs 11·5 months [ 10·1 - 13·1 ] with gefitinib ; HR 0·73 [ 95 % CI 0·58 - 0·92 ] , p=0·0073 ) were significantly longer with afatinib than with gefitinib . Overall survival data are not mature . The most common treatment-related grade 3 or 4 adverse events were diarrhoea ( 20 [ 13 % ] of 160 patients given afatinib vs two [ 1 % ] of 159 given gefitinib ) and rash or acne ( 15 [ 9 % ] patients given afatinib vs five [ 3 % ] of those given gefitinib ) and liver enzyme elevations ( no patients given afatinib vs 14 [ 9 % ] of those given gefitinib ) . Serious treatment-related adverse events occurred in 17 ( 11 % ) patients in the afatinib group and seven ( 4 % ) in the gefitinib group . Ten ( 6 % ) patients in each group discontinued treatment due to drug-related adverse events . 15 ( 9 % ) fatal adverse events occurred in the afatinib group and ten ( 6 % ) in the gefitinib group . All but one of these deaths were considered unrelated to treatment ; one patient in the gefitinib group died from drug-related hepatic and renal failure . INTERPRETATION Afatinib significantly improved outcomes in treatment-naive patients with EGFR-mutated NSCLC 
    Output:
    
agent
We believe that this attempt enables clinicians to choose appropriate treatment easier .
***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 Several studies have shown the efficacy , tolerability , and ease of administration of pemetrexed-an antifolate antineoplastic agent-in  patients with advanced non-small-cell lung cancer . We assessed pemetrexed as maintenance therapy in patients with this disease . METHODS This r and omised double-blind study was undertaken in 83 centres in 20 countries . 663 patients with stage IIIB or IV disease who had not progressed on four cycles of platinum-based chemotherapy  were r and omly assigned ( 2:1 ratio ) to receive pemetrexed ( 500 mg/m(2 ) , day 1 ) plus best supportive care ( n=441 ) or placebo plus best supportive care ( n=222 ) in 21-day cycles until disease progression . Treatment was r and omised with the Simon and Pocock minimisation method . Patients and investigators were masked to treatment . All patients received vitamin B(12 ) , folic acid , and dexamethasone . The primary endpoint of progression-free survival and the secondary endpoint of overall survival were analysed by intention to treat . This study is registered with Clinical Trials.gov , number NCT00102804 . FINDINGS All r and omly assigned participants were analysed . Pemetrexed significantly improved progression-free survival ( 4.3 months [ 95 % CI 4.1 - 4.7 ] vs 2.6 months [ 1.7 - 2.8 ] ; hazard ratio [ HR ] 0.50 , 95 % CI 0.42 - 0.61 , p<0.0001 ) and overall survival ( 13.4 months [ 11.9 - 15.9 ] vs 10.6 months [ 8.7 - 12.0 ] ; HR 0.79 , 0.65 - 0.95 , p=0.012 ) compared with placebo . Treatment discontinuations due to drug-related toxic effects were higher in the pemetrexed group than in the placebo group ( 21 [ 5 % ] vs three [ 1 % ] ) . Drug-related grade three or higher toxic effects were higher with pemetrexed than with placebo ( 70 [ 16 % ] vs nine [ 4 % ] ; p<0.0001 ) , specifically fatigue ( 22 [ 5 % ] vs one [ 1 % ] , p=0.001 ) and neutropenia ( 13 [ 3 % ] vs 0 , p=0.006 ) . No  pemetrexed-related deaths occurred . Relatively fewer patients in the pemetrexed group than in the placebo group received systemic post-discontinuation therapy ( 227 [ 51 % ] vs 149 [ 67 % ] ; p=0.0001 ) . INTERPRETATION Maintenance therapy with pemetrexed is well tolerated and offers improved progression-free and overall survival compared with placebo in patients with advanced non-small-cell lung cancer . FUNDING Eli Lilly Background : Patient-level data from 2 phase III studies in patients with previously untreated , advanced-stage , nonsquamous non – small cell lung cancer ( NSCLC ) were pooled to examine outcomes with bevacizumab and chemotherapy based on age . Methods : Data from patients r and omized to paclitaxel – carboplatin (PC)+bevacizumab in the Eastern Cooperative Oncology Group 4599 ( E4599 ) and PointBreak studies were pooled and compared with E4599 patients r and omized to PC alone . Patients were grouped by age : below 65 , 65 to 74 , 70 to 74 , below 75 , and 75 years or above . A multivariable model was used to calculate hazard ratios ( HRs ) and corresponding 95 % confidence intervals ( CIs ) using time-to-event outcomes . Adverse events ( AEs ) were assessed by age group in each study . Results : The PC+bevacizumab and PC arms comprised 901 and 444 patients , respectively . PC+bevacizumab was associated with significant increases in overall survival relative to PC in patients below 65 years ( hazards ratio [ HR ] , 0.75 ; 95 % confidence interval [ CI ] , 0.62 - 0.89 ) , 65 to 74 years ( HR , 0.80 ; 95 % CI , 0.64 - 1.00 ) , 70 to 74 years ( HR , 0.68 ; 95 % CI , 0.48 - 0.96 ) , and below 75 years ( HR , 0.78 ; 95 % CI , 0.68 - 0.89 ) but not in those aged 75 years or above ( HR , 1.05 ; 95 % CI , 0.70 - 1.57 ) . Increased incidence of grade ≥3 AEs was reported with PC+bevacizumab versus PC in patients below 75 years ( 63 % vs. 48 % ; P<0.05 ) and 75 years or above ( 81 % vs. 56 % ; P < 0.05 ) in E4599 . Conclusions : This analysis suggests that the survival benefits  associated with PC+bevacizumab extend to patient subgroups below 75 years with advanced-stage NSCLC ; no benefit , however , was observed for bevacizumab-eligible patients who were 75 years or above BACKGROUND We conducted a r and omized , placebo-controlled , double-blind trial to determine whether the epidermal growth factor receptor inhibitor erlotinib prolongs survival in non-small-cell lung cancer after the failure of first-line or second-line chemotherapy . METHODS Patients with stage IIIB or IV non-small-cell lung cancer , with performance status from 0 to 3 , were eligible if they had received one or two prior chemotherapy regimens .  The patients were stratified according to center , performance status , response to prior chemotherapy , number of prior regimens , and prior platinum-based therapy and were r and omly assigned in a 2:1 ratio to receive oral erlotinib , at a dose of 150 mg daily , or placebo . RESULTS The median age of the 731 patients who underwent r and omization was 61.4 years ; 49 percent had received two prior chemotherapy regimens , and 93 percent had received platinum-based chemotherapy .  The response rate was 8.9 percent in the erlotinib group and less than 1 percent in the placebo group ( P<0.001 ) ; the median duration of the response was 7.9 months and 3.7 months , respectively . Progression-free survival was 2.2 months and 1.8 months , respectively ( hazard ratio , 0.61 , adjusted for stratification categories ; P<0.001 ) . Overall survival was 6.7 months and 4.7 months , respectively ( hazard ratio , 0.70 ; P<0.001 ) , in favor of erlotinib . Five percent of patients discontinued erlotinib because of toxic effects . CONCLUSIONS Erlotinib can prolong survival in patients with non-small-cell lung cancer after first-line or second-line chemotherapy This r and omised multicentre trial was conducted to establish the optimal duration of palliative chemotherapy in advanced non-small-cell lung cancer ( NSCLC ) . We compared a policy of three vs six courses of new-generation platinum-based combination chemotherapy with regard to effects on quality of life ( QoL ) and survival .  Patients with stage IIIB or IV NSCLC and WHO performance status ( PS ) 0–2 were r and omised to receive three ( C3 ) or six ( C6 ) courses of carboplatin ( area under the curve ( AUC ) 4 , Chatelut 's formula , equivalent to Calvert 's AUC 5 ) on day 1 and vinorelbine 25 mg m−2 on days 1 and 8 of a 3-week cycle . Key end points were QoL at 18 weeks , measured with EORTC Quality of Life Question naire (QLQ)-C30 and QLQ-LC13 , and overall survival . Secondary end points were progression-free survival and need of palliative radiotherapy . Two hundred and ninety-seven patients were r and omised ( C3 150 , C6 147 ) . Their median age was 65 years , 30 % had PS 2 and 76 % stage IV disease . Seventy-eight and 54 % of C3 and C6 patients , respectively , completed all scheduled chemotherapy courses . Compliance with QoL question naires was 88 % . There were no significant group differences in global QoL , pain or fatigue up to 26 weeks . The dyspnoea palliation rate was lower in the C3 arm at 18 and 26 weeks ( P<0.05 ) , but this finding was inconsistent across different methods of analysis . Median survival in the C3 group was 28 vs 32 weeks in the C6 group ( P=0.75 , HR 1.04 , 95 % CI 0.82–1.31 ) . One- and 2-year survival rates were 25 and 9 % vs 25 and 5 % in the C3 and C6 arm , respectively . Median progression-free survival was 16 and 21 weeks in the C3 and C6 groups , respectively ( P=0.21 , HR 0.86 , 95 % CI 0.68–1.08 ) . In conclusion , palliative chemotherapy with carboplatin and vinorelbine beyond three courses conveys no survival or consistent QoL benefits in advanced NSCLC BACKGROUND The irreversible ErbB family blocker afatinib and the reversible EGFR tyrosine kinase inhibitor gefitinib are approved for first-line treatment of EGFR mutation-positive non-small-cell lung cancer ( NSCLC ) . We aim ed to compare the efficacy and safety of afatinib and gefitinib in this setting . METHODS This multicentre , international , open-label , exploratory , r and omised controlled phase 2B trial ( LUX-Lung 7 ) was done at 64 centres in 13 countries . Treatment-naive patients with stage IIIB or IV NSCLC and a common EGFR mutation ( exon 19 deletion or Leu858Arg ) were r and omly assigned ( 1:1 ) to receive afatinib ( 40 mg per day ) or gefitinib ( 250 mg per day ) until disease progression , or beyond if deemed beneficial by the investigator . R and omisation , stratified by EGFR mutation type and status of brain metastases , was done central ly using a vali date d number generating system implemented via an interactive voice or web-based response system with a block size of four . Clinicians and patients were not masked to treatment allocation ; independent review of tumour response was done in a blinded manner . Co primary endpoints were progression-free survival by independent central review , time-to-treatment failure , and overall survival . Efficacy analyses were done in the intention-to-treat population and safety analyses were done in patients who received at least one dose of study drug . This ongoing study is registered with Clinical Trials.gov , number NCT01466660 . FINDINGS Between Dec 13 , 2011 , and Aug 8 , 2013 , 319 patients were r and omly assigned ( 160 to afatinib and 159 to gefitinib ) . Median follow-up was 27·3 months ( IQR 15·3 - 33·9 ) . Progression-free survival ( median 11·0 months [ 95 % CI 10·6 - 12·9 ] with afatinib vs 10·9 months [ 9·1 - 11·5 ] with gefitinib ; hazard ratio [ HR ] 0·73 [ 95 % CI 0·57 - 0·95 ] , p=0·017 ) and time-to-treatment failure ( median 13·7 months [ 95 % CI 11·9 - 15·0 ] with afatinib vs 11·5 months [ 10·1 - 13·1 ] with gefitinib ; HR 0·73 [ 95 % CI 0·58 - 0·92 ] , p=0·0073 ) were significantly longer with afatinib than with gefitinib . Overall survival data are not mature . The most common treatment-related grade 3 or 4 adverse events were diarrhoea ( 20 [ 13 % ] of 160 patients given afatinib vs two [ 1 % ] of 159 given gefitinib ) and rash or acne ( 15 [ 9 % ] patients given afatinib vs five [ 3 % ] of those given gefitinib ) and liver enzyme elevations ( no patients given afatinib vs 14 [ 9 % ] of those given gefitinib ) . Serious treatment-related adverse events occurred in 17 ( 11 % ) patients in the afatinib group and seven ( 4 % ) in the gefitinib group . Ten ( 6 % ) patients in each group discontinued treatment due to drug-related adverse events . 15 ( 9 % ) fatal adverse events occurred in the afatinib group and ten ( 6 % ) in the gefitinib group . All but one of these deaths were considered unrelated to treatment ; one patient in the gefitinib group died from drug-related hepatic and renal failure . INTERPRETATION Afatinib significantly improved outcomes in treatment-naive patients with EGFR-mutated NSCLC 
    Output:
    