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 Necitumumab is a second-generation recombinant human immunoglobulin G1 EGFR monoclonal antibody that competitively inhibits lig and binding . We aim ed to compare necitumumab plus pemetrexed and cisplatin with pemetrexed and cisplatin alone in patients with previously untreated , stage IV , non-squamous non-small-cell lung cancer ( NSCLC ) . METHODS We did this r and omised , open-label , controlled phase 3 study at 103 sites in 20 countries . Patients aged 18 years or older , with an Eastern Cooperative Oncology Group ( ECOG ) performance status of 0 - 2 and adequate organ function , were r and omly assigned 1:1 to treatment with a block r and omisation scheme ( block size of four ) via a telephone-based interactive voice-response system or interactive web-response system . Patients received either cisplatin 75 mg/m(2 ) and pemetrexed 500 mg/m(2 ) on day 1 of a 3-week cycle for a maximum of six cycles alone , or with necitumumab 800 mg on days 1 and 8 . Necitumumab was continued after the end of chemotherapy until disease progression or unacceptable toxic effects . R and omisation was stratified by smoking history , ECOG performance status , disease histology , and geographical region . Patients and study investigators were not masked to group assignment . The primary endpoint was overall survival . Efficacy analyses were by intention to treat . This trial is registered with Clinical Trials.gov , number NCT00982111 . FINDINGS Between Nov 11 , 2009 , and Feb 2 , 2011 , we r and omly assigned 633 patients to receive either necitumumab plus pemetrexed and cisplatin ( n=315 ) or pemetrexed and cisplatin alone ( n=318 ) . Enrolment was stopped on Feb 2 , 2011 , after a recommendation from the independent data monitoring committee . There was no significant difference in overall survival between treatment groups , with a median overall survival of 11·3 months ( 95 % CI 9·5 - 13·4 ) in the necitumumab plus pemetrexed and cisplatin group versus 11·5 months ( 10·1 - 13·1 ) in the pemetrexed and cisplatin group ( hazard ratio 1·01 [ 95 % CI 0·84 - 1·21 ] ; p=0·96 ) . The incidence of grade 3 or worse adverse events , including deaths , was higher in the necitumumab plus pemetrexed and cisplatin group than in the pemetrexed and cisplatin group ; in particular , deaths regarded as related to study drug were reported in 15 ( 5 % ) of 304 patients in the necitumumab group versus nine ( 3 % ) of 312 patients in the pemetrexed and cisplatin group . Serious adverse events were likewise more frequent in the necitumumab plus pemetrexed and cisplatin group than in the pemetrexed and cisplatin group ( 155 [ 51 % ] of 304 vs 127 [ 41 % ] of 312 patients ) . Patients in the necitumumab plus pemetrexed and cisplatin group had more grade 3 - 4 rash ( 45 [ 15 % ] of 304 vs one [ < 1 % ] of 312 patients in the pemetrexed and cisplatin alone group ) , hypomagnesaemia ( 23 [ 8 % ] vs seven [ 2 % ] patients ) , and grade 3 or higher venous thromboembolic events ( 23 [ 8 % ] vs 11 [ 4 % ] patients ) than did those in the pemetrexed and cisplatin alone group . INTERPRETATION Our findings show no evidence to suggest that the addition of necitumumab to pemetrexed and cisplatin increases survival of previously untreated patients with stage IV non-squamous NSCLC . Unless future studies identify potentially useful predictive biomarkers , necitumumab is unlikely to provide benefit in this patient population when combined with pemetrexed and cisplatin . FUNDING Eli Lilly and Company BACKGROUND The study compared the efficacy of a first-line treatment with day 1 i.v . vinorelbine ( NVBiv ) and day 8 oral vinorelbine ( NVBo ) versus docetaxel ( DCT ) in a cisplatin-based combination in advanced non-small-cell lung cancer , in terms of time to treatment failure ( TTF ) , overall response , progression-free survival ( PFS ) , overall survival ( OS ) , tolerance and quality of life ( QoL ) . METHODS Patients were r and omly assigned to receive cisplatin 80 mg/m2 with NVBiv 30 mg/m2 on day 1 and NVBo 80 mg/m2 on day 8 every 3 weeks , after a first cycle of NVBiv 25 mg/m2 on day 1 and NVBo 60 mg/m2 on day 8 ( arm A ) or cisplatin 75 mg/m2 and DCT 75 mg/m2 on day 1 every 3 weeks ( arm B ) , for a maximum of six cycles in both arms . RESULTS From 2 February 2004 to 1 January 2006 , 390 patients were entered in a r and omised study and 381 were treated . The patient characteristics are as follows ( arms A/B ) : metastatic ( % ) 80.5/84.8 ; patients with three or more organs involved  ( % ) 45.3/40.8 ; median age 59.4/62.1 years ; male 139/146 ; squamous ( % ) 34.2/33.5 ; adenocarcinoma ( % ) 41.6/39.3 ; median TTF ( arms A/B in months ) [ 95 % confidence interval ( CI ) ] : 3.2 ( 3.0 - 4.2 ) , 4.1 ( 3.4 - 4.5 ) ( P = 0.19 ) ; overall response ( arms A/B ) ( 95 % CI ) : 27.4 % ( 21.2 % to 34.2 % ) , 27.2 % ( 21.0 % to 34.2 % ) ; median PFS ( arms A/B in months ) ( 95 % CI ) : 4.9 ( 4.4 - 5.9 ) , 5.1 ( 4.3 - 6.1 ) ( P = 0.99 ) and median OS ( arms A/B in months ) ( 95 % CI ) : 9.9 ( 8.4 - 11.6 ) , 9.8 ( 8.8 - 11.5 ) ( P = 0.58 ) . The median survival for squamous histology was 8.87/9.82 months and for adenocarcinoma 11.73/11.60 months for arms A and B , respectively . Main haematological toxicity was grade 3 - 4 neutropenia : 24.4 % ( arm A ) and 28.8 % ( arm B ) . QoL as measured by the Lung Cancer Symptom Scale was similar in both arms . CONCLUSIONS Both arms provided similar efficacy in terms of response , time-related parameters and QoL , with an acceptable tolerance profile . In the current Global Lung Oncology Branch trial 3 , NVBo was shown to be effective as a substitute for the i.v . formulation . This can relieve the burden of the i.v . injection on day 8 and can optimise the hospital 's re sources and improve patient convenience BACKGROUND Necitumumab is a second-generation , recombinant , human immunoglobulin G1 EGFR antibody . In this study , we aim ed to compare treatment with necitumumab plus gemcitabine and cisplatin versus gemcitabine and cisplatin alone in patients with previously untreated stage IV squamous non-small-cell lung cancer . METHODS We did this open-label , r and omised phase 3 study at 184 investigative sites in 26 countries . Patients aged 18 years or older with histologically or cytologically confirmed stage IV squamous non-small-cell lung cancer , with an Eastern Cooperative Oncology Group ( ECOG ) performance status of 0 - 2 and adequate organ function and who had not received previous chemotherapy for their disease were eligible for inclusion . Enrolled patients were r and omly assigned central ly 1:1 to a maximum of six 3-week cycles of gemcitabine and cisplastin chemotherapy with or without necitumumab according to a block r and omisation scheme ( block size of four ) by a telephone-based interactive voice response system or interactive web response system . Chemotherapy was gemcitabine 1250 mg/m(2 ) administered intravenously over 30 min on days 1 and 8 of a 3-week cycle and cisplatin 75 mg/m(2 ) administered intravenously over 120 min on day 1 of a 3-week cycle . Necitumumab 800 mg , administered intravenously over a minimum of 50 min on days 1 and 8 , was continued after the end of chemotherapy until  disease progression or intolerable toxic side-effects occurred . R and omisation was stratified by ECOG performance status and geographical region . Neither physicians nor patients were masked to group assignment because of the expected occurrence of acne-like rash -- a class effect of EGFR antibodies -- that would have unmasked most patients and investigators to treatment . The primary endpoint was overall survival , analysed by intention to treat . We report the final clinical analysis . This study is registered with Clinical Trials.gov , number NCT00981058 . FINDINGS Between Jan 7 , 2010 , and Feb 22 , 2012 , we enrolled 1093 patients and r and omly assigned them to receive necitumumab plus gemcitabine and cisplatin ( n=545 ) or gemcitabine and cisplatin ( n=548 ) . Overall survival was significantly longer in the necitumumab plus gemcitabine and cisplatin group than in the gemcitabine and cisplatin alone group ( median 11·5 months [ 95 % CI 10·4 - 12·6 ] ) vs 9·9 months [ 8·9 - 11·1 ] ; stratified hazard ratio 0·84 [ 95 % CI 0·74 - 0·96 ; p=0·01 ] ) . In the necitumumab plus gemcitabine and cisplatin group , the number of patients with at least one grade 3 or worse adverse event was higher ( 388 [ 72 % ] of 538 patients ) than in the gemcitabine and cisplatin group ( 333 [ 62 % ] of 541 ) , as was the incidence of serious adverse events ( 257 [ 48 % ] of 538 patients vs 203 [ 38 % ] of 541 ) . More patients in the necitumumab plus gemcitabine and cisplatin group had grade 3 - 4 hypomagnesaemia ( 47 [ 9 % ] of 538 patients in the necitumumab plus gemcitabine and cisplatin group vs six [ 1 % ] of 541 in the gemcitabine and cisplatin group ) and grade 3 rash ( 20 [ 4 % ] vs one [ < 1 % ] ) . Including events related to disease progression , adverse events with an outcome of death were reported for 66 ( 12 % ) of 538 patients in the necitumumab plus gemcitabine and cisplatin group and 57 ( 11 % ) of 541 patients in the gemcitabine and cisplatin group ; these were deemed to be related to study drugs in 15 ( 3 % ) and ten ( 2 % ) patients , respectively . Overall , we found that the safety profile of necitumumab plus gemcitabine and cisplatin was acceptable and in line with expectations . INTERPRETATION Our findings show that the addition of necitumumab to gemcitabine and cisplatin chemotherapy improves overall survival in patients with advanced squamous non-small-cell lung cancer and represents a new first-line treatment option for this disease . FUNDING Eli Lilly and Company PURPOSE Cancers rely on angiogenesis for their growth and dissemination . We hypothesized that thalidomide , an oral antiangiogenic agent , when combined with chemotherapy , and as maintenance treatment , would improve survival in patients with advanced non-small-cell lung cancer ( NSCLC ) . PATIENTS AND METHODS Seven hundred twenty-two patients were r and omly assigned to receive placebo or thalidomide capsules 100 to 200 mg daily for up to 2 years . All patients received gemcitabine and carboplatin every 3 weeks for up to four cycles . End points were overall survival ( OS ) , progression-free survival ( PFS ) , response rate , grade 3/4 toxicity , and quality of life ( QoL ) . RESULTS The median OS rates were 8.9 months ( placebo ) and 8.5 months ( thalidomide ) . The hazard ratio ( HR ) was 1.13 ( 95 % CI , 0.97 to 1.32 ; P = .12 ) . The 2-year survival rate was 16 % and 12 % 
    Output:
    
agent
In the third-line setting , for patients who have not received erlotinib or gefitinib , treatment with erlotinib is recommended .
There are insufficient data to recommend routine third-line cytotoxic therapy .
***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 Necitumumab is a second-generation recombinant human immunoglobulin G1 EGFR monoclonal antibody that competitively inhibits lig and binding . We aim ed to compare necitumumab plus pemetrexed and cisplatin with pemetrexed and cisplatin alone in patients with previously untreated , stage IV , non-squamous non-small-cell lung cancer ( NSCLC ) . METHODS We did this r and omised , open-label , controlled phase 3 study at 103 sites in 20 countries . Patients aged 18 years or older , with an Eastern Cooperative Oncology Group ( ECOG ) performance status of 0 - 2 and adequate organ function , were r and omly assigned 1:1 to treatment with a block r and omisation scheme ( block size of four ) via a telephone-based interactive voice-response system or interactive web-response system . Patients received either cisplatin 75 mg/m(2 ) and pemetrexed 500 mg/m(2 ) on day 1 of a 3-week cycle for a maximum of six cycles alone , or with necitumumab 800 mg on days 1 and 8 . Necitumumab was continued after the end of chemotherapy until disease progression or unacceptable toxic effects . R and omisation was stratified by smoking history , ECOG performance status , disease histology , and geographical region . Patients and study investigators were not masked to group assignment . The primary endpoint was overall survival . Efficacy analyses were by intention to treat . This trial is registered with Clinical Trials.gov , number NCT00982111 . FINDINGS Between Nov 11 , 2009 , and Feb 2 , 2011 , we r and omly assigned 633 patients to receive either necitumumab plus pemetrexed and cisplatin ( n=315 ) or pemetrexed and cisplatin alone ( n=318 ) . Enrolment was stopped on Feb 2 , 2011 , after a recommendation from the independent data monitoring committee . There was no significant difference in overall survival between treatment groups , with a median overall survival of 11·3 months ( 95 % CI 9·5 - 13·4 ) in the necitumumab plus pemetrexed and cisplatin group versus 11·5 months ( 10·1 - 13·1 ) in the pemetrexed and cisplatin group ( hazard ratio 1·01 [ 95 % CI 0·84 - 1·21 ] ; p=0·96 ) . The incidence of grade 3 or worse adverse events , including deaths , was higher in the necitumumab plus pemetrexed and cisplatin group than in the pemetrexed and cisplatin group ; in particular , deaths regarded as related to study drug were reported in 15 ( 5 % ) of 304 patients in the necitumumab group versus nine ( 3 % ) of 312 patients in the pemetrexed and cisplatin group . Serious adverse events were likewise more frequent in the necitumumab plus pemetrexed and cisplatin group than in the pemetrexed and cisplatin group ( 155 [ 51 % ] of 304 vs 127 [ 41 % ] of 312 patients ) . Patients in the necitumumab plus pemetrexed and cisplatin group had more grade 3 - 4 rash ( 45 [ 15 % ] of 304 vs one [ < 1 % ] of 312 patients in the pemetrexed and cisplatin alone group ) , hypomagnesaemia ( 23 [ 8 % ] vs seven [ 2 % ] patients ) , and grade 3 or higher venous thromboembolic events ( 23 [ 8 % ] vs 11 [ 4 % ] patients ) than did those in the pemetrexed and cisplatin alone group . INTERPRETATION Our findings show no evidence to suggest that the addition of necitumumab to pemetrexed and cisplatin increases survival of previously untreated patients with stage IV non-squamous NSCLC . Unless future studies identify potentially useful predictive biomarkers , necitumumab is unlikely to provide benefit in this patient population when combined with pemetrexed and cisplatin . FUNDING Eli Lilly and Company BACKGROUND The study compared the efficacy of a first-line treatment with day 1 i.v . vinorelbine ( NVBiv ) and day 8 oral vinorelbine ( NVBo ) versus docetaxel ( DCT ) in a cisplatin-based combination in advanced non-small-cell lung cancer , in terms of time to treatment failure ( TTF ) , overall response , progression-free survival ( PFS ) , overall survival ( OS ) , tolerance and quality of life ( QoL ) . METHODS Patients were r and omly assigned to receive cisplatin 80 mg/m2 with NVBiv 30 mg/m2 on day 1 and NVBo 80 mg/m2 on day 8 every 3 weeks , after a first cycle of NVBiv 25 mg/m2 on day 1 and NVBo 60 mg/m2 on day 8 ( arm A ) or cisplatin 75 mg/m2 and DCT 75 mg/m2 on day 1 every 3 weeks ( arm B ) , for a maximum of six cycles in both arms . RESULTS From 2 February 2004 to 1 January 2006 , 390 patients were entered in a r and omised study and 381 were treated . The patient characteristics are as follows ( arms A/B ) : metastatic ( % ) 80.5/84.8 ; patients with three or more organs involved  ( % ) 45.3/40.8 ; median age 59.4/62.1 years ; male 139/146 ; squamous ( % ) 34.2/33.5 ; adenocarcinoma ( % ) 41.6/39.3 ; median TTF ( arms A/B in months ) [ 95 % confidence interval ( CI ) ] : 3.2 ( 3.0 - 4.2 ) , 4.1 ( 3.4 - 4.5 ) ( P = 0.19 ) ; overall response ( arms A/B ) ( 95 % CI ) : 27.4 % ( 21.2 % to 34.2 % ) , 27.2 % ( 21.0 % to 34.2 % ) ; median PFS ( arms A/B in months ) ( 95 % CI ) : 4.9 ( 4.4 - 5.9 ) , 5.1 ( 4.3 - 6.1 ) ( P = 0.99 ) and median OS ( arms A/B in months ) ( 95 % CI ) : 9.9 ( 8.4 - 11.6 ) , 9.8 ( 8.8 - 11.5 ) ( P = 0.58 ) . The median survival for squamous histology was 8.87/9.82 months and for adenocarcinoma 11.73/11.60 months for arms A and B , respectively . Main haematological toxicity was grade 3 - 4 neutropenia : 24.4 % ( arm A ) and 28.8 % ( arm B ) . QoL as measured by the Lung Cancer Symptom Scale was similar in both arms . CONCLUSIONS Both arms provided similar efficacy in terms of response , time-related parameters and QoL , with an acceptable tolerance profile . In the current Global Lung Oncology Branch trial 3 , NVBo was shown to be effective as a substitute for the i.v . formulation . This can relieve the burden of the i.v . injection on day 8 and can optimise the hospital 's re sources and improve patient convenience BACKGROUND Necitumumab is a second-generation , recombinant , human immunoglobulin G1 EGFR antibody . In this study , we aim ed to compare treatment with necitumumab plus gemcitabine and cisplatin versus gemcitabine and cisplatin alone in patients with previously untreated stage IV squamous non-small-cell lung cancer . METHODS We did this open-label , r and omised phase 3 study at 184 investigative sites in 26 countries . Patients aged 18 years or older with histologically or cytologically confirmed stage IV squamous non-small-cell lung cancer , with an Eastern Cooperative Oncology Group ( ECOG ) performance status of 0 - 2 and adequate organ function and who had not received previous chemotherapy for their disease were eligible for inclusion . Enrolled patients were r and omly assigned central ly 1:1 to a maximum of six 3-week cycles of gemcitabine and cisplastin chemotherapy with or without necitumumab according to a block r and omisation scheme ( block size of four ) by a telephone-based interactive voice response system or interactive web response system . Chemotherapy was gemcitabine 1250 mg/m(2 ) administered intravenously over 30 min on days 1 and 8 of a 3-week cycle and cisplatin 75 mg/m(2 ) administered intravenously over 120 min on day 1 of a 3-week cycle . Necitumumab 800 mg , administered intravenously over a minimum of 50 min on days 1 and 8 , was continued after the end of chemotherapy until  disease progression or intolerable toxic side-effects occurred . R and omisation was stratified by ECOG performance status and geographical region . Neither physicians nor patients were masked to group assignment because of the expected occurrence of acne-like rash -- a class effect of EGFR antibodies -- that would have unmasked most patients and investigators to treatment . The primary endpoint was overall survival , analysed by intention to treat . We report the final clinical analysis . This study is registered with Clinical Trials.gov , number NCT00981058 . FINDINGS Between Jan 7 , 2010 , and Feb 22 , 2012 , we enrolled 1093 patients and r and omly assigned them to receive necitumumab plus gemcitabine and cisplatin ( n=545 ) or gemcitabine and cisplatin ( n=548 ) . Overall survival was significantly longer in the necitumumab plus gemcitabine and cisplatin group than in the gemcitabine and cisplatin alone group ( median 11·5 months [ 95 % CI 10·4 - 12·6 ] ) vs 9·9 months [ 8·9 - 11·1 ] ; stratified hazard ratio 0·84 [ 95 % CI 0·74 - 0·96 ; p=0·01 ] ) . In the necitumumab plus gemcitabine and cisplatin group , the number of patients with at least one grade 3 or worse adverse event was higher ( 388 [ 72 % ] of 538 patients ) than in the gemcitabine and cisplatin group ( 333 [ 62 % ] of 541 ) , as was the incidence of serious adverse events ( 257 [ 48 % ] of 538 patients vs 203 [ 38 % ] of 541 ) . More patients in the necitumumab plus gemcitabine and cisplatin group had grade 3 - 4 hypomagnesaemia ( 47 [ 9 % ] of 538 patients in the necitumumab plus gemcitabine and cisplatin group vs six [ 1 % ] of 541 in the gemcitabine and cisplatin group ) and grade 3 rash ( 20 [ 4 % ] vs one [ < 1 % ] ) . Including events related to disease progression , adverse events with an outcome of death were reported for 66 ( 12 % ) of 538 patients in the necitumumab plus gemcitabine and cisplatin group and 57 ( 11 % ) of 541 patients in the gemcitabine and cisplatin group ; these were deemed to be related to study drugs in 15 ( 3 % ) and ten ( 2 % ) patients , respectively . Overall , we found that the safety profile of necitumumab plus gemcitabine and cisplatin was acceptable and in line with expectations . INTERPRETATION Our findings show that the addition of necitumumab to gemcitabine and cisplatin chemotherapy improves overall survival in patients with advanced squamous non-small-cell lung cancer and represents a new first-line treatment option for this disease . FUNDING Eli Lilly and Company PURPOSE Cancers rely on angiogenesis for their growth and dissemination . We hypothesized that thalidomide , an oral antiangiogenic agent , when combined with chemotherapy , and as maintenance treatment , would improve survival in patients with advanced non-small-cell lung cancer ( NSCLC ) . PATIENTS AND METHODS Seven hundred twenty-two patients were r and omly assigned to receive placebo or thalidomide capsules 100 to 200 mg daily for up to 2 years . All patients received gemcitabine and carboplatin every 3 weeks for up to four cycles . End points were overall survival ( OS ) , progression-free survival ( PFS ) , response rate , grade 3/4 toxicity , and quality of life ( QoL ) . RESULTS The median OS rates were 8.9 months ( placebo ) and 8.5 months ( thalidomide ) . The hazard ratio ( HR ) was 1.13 ( 95 % CI , 0.97 to 1.32 ; P = .12 ) . The 2-year survival rate was 16 % and 12 % 
    Output:
    