***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 Introduction : This study compared survival without toxicity in patients with advanced , nonsquamous non-small cell lung cancer who were treated with first-line pemetrexed/carboplatin or docetaxel/carboplatin .  Methods : This multicenter , open-label , parallel-group , phase 3 trial comprised patients r and omized ( 1:1 ) to pemetrexed/carboplatin ( n = 128 ) or docetaxel/carboplatin ( n = 132 ) . Patients received treatment on day 1 of each 21-day cycle ( maximum of six cycles ) . Treatment included carboplatin ( area under the curve = 5 mg/ml × min ) and pemetrexed ( 500 mg/m2 ) or docetaxel ( 75 mg/m2 ) . The primary outcome measure , survival without treatment-emergent grade 3/4 toxicity , was defined as the time from r and omization to the first treatment-emergent grade 3/4 adverse event or death and was analyzed using a log-rank test . The analysis population included 106 patients in the pemetrexed/carboplatin ( Pem/Carb ) group and 105 patients in the docetaxel/carboplatin ( Doc/Carb ) group . Results : Survival without treatment-emergent grade 3/4 toxicity was significantly longer in the Pem/Carb versus the Doc/Carb group ( log-rank p < 0.001 ; median survival without treatment-emergent grade 3/4 toxicity : 3.2 versus 0.7 months ; adjusted hazard ratio = 0.45 [ 95 % confidence interval : 0.34–0.61 ] ) . Overall survival was similar in the Pem/Carb versus the Doc/Carb group ( log-rank p = 0.934 ; median survival : 14.9 versus 14.7 months ; adjusted hazard ratio = 0.93 [ 95 % confidence interval : 0.66–1.32 ] ) . Compared with the Doc/Carb group , fewer patients in the Pem/Carb group experienced grade 3/4 drug-related , treatment-emergent neutropenia , leukopenia , or febrile neutropenia , and more patients experienced anemia and thrombocytopenia . There were three study drug-related deaths during treatment in each group . Conclusions : The favorable benefit-to-risk profile of pemetrexed/carboplatin suggests that pemetrexed/carboplatin is an appropriate first-line treatment option for chemonaïve patients with advanced , nonsquamous non-small cell lung cancer Background Subgroup analyses of r and omized studies have consistently shown that pemetrexed is exclusively effective in non-small-cell lung cancer ( NSCLC ) other than squamous cell carcinoma and the combination of pemetrexed and platinum agents is recommended for first-line chemotherapy in advanced non-squamous NSCLC ; however , there have been few prospect i ve studies of a selected population . Patients and methods This was a single-arm phase II study of carboplatin and pemetrexed in Japanese patients with chemo-naive advanced non-squamous NSCLC . Patients received six cycles of pemetrexed ( 500 mg/m2 ) combined with carboplatin ( area under the curve : AUC 6 ) every 3 weeks . Maintenance chemotherapy with pemetrexed was permitted in patients whose disease did not progress after combination chemotherapy . The primary endpoint was the response rate , and secondary endpoints were safety and survival . Results Fifty-one patients were enrolled between November 2009 and March 2011 , and 49 patients were evaluable for both safety and efficacy . All but one patient had adenocarcinoma histology . Forty-four ( 90 % ) patients completed four cycles , and 33 ( 67 % ) completed six cycles of chemotherapy . Partial response was achieved in 25 patients ( response rate : 51 % ) and stable disease in 18 patients ( 37 % ) . Median progression-free survival ( PFS ) and overall survival ( OS ) were 6.3 months and 24.3 months , respectively . The median PFS and OS were 7.9 months and 24.3 months in patients with epidermal growth factor receptor ( EGFR ) mutation , and 6.3 months and 21.0 months in patients with EGFR wild type or unknown . There were no statistical differences between EGFR mutants and non-mutants for both PFS ( p = 0.09 ) and OS ( p = 0.23 ) . Grade 3/4 neutropenia and thrombocytopenia were observed in 16 ( 33 % ) and 9 ( 18 % ) patients , respectively . Non-hematologic toxicities were generally mild , and there were no treatment-related deaths . Conclusions The combination of carboplatin and pemetrexed was safe and effective in advanced non-squamous NSCLC . Although the sample size was small , our results indicate that pemetrexed is a key drug for advanced non-squamous NSCLC , irrespective of the EGFR mutation status ( UMIN-CTR number 000002451 ) Background The efficacy and safety of axitinib , a potent and selective second-generation inhibitor of vascular endothelial growth factor receptors 1 , 2 , and 3 in combination with pemetrexed and cisplatin was evaluated in patients with advanced non-squamous non – small-cell lung cancer ( NSCLC ) . Methods Overall , 170 patients were r and omly assigned to receive axitinib at a starting dose of 5-mg twice daily continuously plus pemetrexed 500 mg/m2 and cisplatin 75 mg/m2 on day 1 of up to six 21-day cycles ( arm I ) ; axitinib on days 2 through 19 of each cycle plus pemetrexed/cisplatin ( arm II ) ; or pemetrexed/cisplatin alone ( arm III ) . The primary endpoint was progression-free survival ( PFS ) . Results Median PFS was 8.0 , 7.9 , and 7.1 months in arms I , II , and III , respectively ( hazard ratio : arms I vs. III , 0.89 [ P = 0.36 ] and arms II vs. III , 1.02 [ P = 0.54 ] ) . Median overall survival was 17.0 months ( arm I ) , 14.7 months ( arm II ) , and 15.9 months ( arm III ) . Objective response rates ( ORRs ) for axitinib-containing arms were 45.5 % ( arm I ) and 39.7 % ( arm II ) compared with 26.3 % for pemetrexed/cisplatin alone ( arm III ) . Gastrointestinal disorders and fatigue were frequently reported across all treatment arms . The most common all-causality grade ≥3 adverse events were hypertension in axitinib-containing arms ( 20 % and 17 % , arms I and II , respectively ) and fatigue with pemetrexed/cisplatin alone ( 16 % ) . Conclusion Axitinib in combination with pemetrexed/cisplatin was generally well tolerated . Axitinib combinations result ed in non-significant differences in PFS and numerically higher ORR compared with chemotherapy alone in advanced NSCLC.Trial registration Clinical Trials.gov : NCT00768755 ( October 7 , 2008 ) BACKGROUND Recent studies of pemetrexed have identified a predictive role for non-small cell lung cancer ( NSCLC ) histology . We further review ed the differential efficacy of pemetrexed according to histology in two large , phase III NSCLC trials . METHODS One study tested pemetrexed versus docetaxel in previously treated patients ( n = 571 ) and the other tested cisplatin plus pemetrexed versus cisplatin plus gemcitabine in chemotherapy-naive patients ( n = 1,725 ) with advanced NSCLC . Cox proportional hazard models were used to test for covariate-adjusted treatment-by-histology interactions ( THIs ) for overall survival ( OS ) and progression-free survival ( PFS ) . For each histologic subgroup , the Kaplan-Meier method was used to estimate unadjusted within-arm medians , and Cox models were used to estimate covariate-adjusted between-arm hazard ratios ( HRs ) . RESULTS In both studies , treatment arms were well balanced for histology . THIs were statistically significant ( p < .005 ) for both OS and PFS . Nonsquamous patients treated with pemetrexed-based therapy experienced longer survival than the comparators ( HR , 0.78 and 0.84 , respectively ) , whereas squamous patients had shorter survival ( HR , 1.56 and 1.23 , respectively ) . Whereas the efficacy of pemetrexed regimens differed according to histology , it did not differ for docetaxel or for cisplatin plus gemcitabine . Pemetrexed was well tolerated across histologic groups . CONCLUSIONS The consistency of these results across studies confirms the predictive effect of histology for pemetrexed and the survival advantage for pemetrexed in patients with nonsquamous histology . These analyses suggest pemetrexed should not be recommended for the treatment of squamous cell carcinoma , but , because of efficacy and safety 
    Output:
    
Conclusion Pemetrexed plus platinum doublet regimen is an efficacious treatment for advanced nonsquamous NSCLC patients .
Our findings support the use of pemetrexed plus platinum doublet regimen as first-line treatment in advanced nonsquamous NSCLC patients because of its potential survival benefits