***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 7012 Background : NSCLC is a tumor with high EGFR-expression in the majority of cases . Since there is still a need for improvement in the outcome of patients with NSCLC , we evaluated the addition of cetuximab ( Erbitux ) , an IgG1 monoclonal antibody targeting the EGFR , to CV , a st and ard chemotherapy in NSCLC , in first-line treatment of patients with NSCLC . Combinations of cetuximab and chemotherapy have shown to be effective and safe in several EGFR-expressing tumors such as colorectal cancer and head and neck cancer . METHODS Neither of the patients had received prior chemotherapy . All patients were treated with C 80 mg/m2 d1 and V 25 mg/m2 d1 and 8 , q3 and were r and omized to either receive additional cetuximab 400 mg/m2 week 1 and 250 mg/m2 weekly thereafter ( arm A ) or no additional treatment ( arm B ) . RESULTS 101/112 ( 90 % ) of pts screened had EGFR-expressing tumors . Enrollment was completed with a total of 86 pts : 43 ( 10 f , 33 m ) in arm A and 43 ( 12 f , 31 m ) in arm B. The following patient/tumor characteristics were similar in both treatment arms : median age of 58 y ( 34 - 75 ) , median KPS of 90 , 92 % of patients had stage IV NSCLC , 42 % had adenocarcinoma and 42 % had squamous cell carcinoma . Relevant grade 3/4 adverse events in arm A ( B ) were : leucopenia 64.3 % ( 51.2 ) , nausea/vomiting 16.7 % ( 14.0 ) , asthenia/fatigue 16.7 % ( 2.3 ) , infection 11.9 % ( 4.7 ) , fever/chills 9.5 % ( 7.0 ) , thrombocytopenia 7.1 % ( 4.7 ) , acne-like rash 4.8 % ( 0 ) , diarrhea 2.4 % ( 0 ) . Confirmed response rates based on preliminary assesment of 41 pts in arm A were 31.7 % ( C.I. : 17.5 - 46.0 ) [ 13 PR , 18 SD , 3 PD ] , and of 40 pts in arm B : 20.0 % ( C.I. : 7.6 -32.4 ) [ 8 PR , 17 SD , 13 PD ] , TTP based on 79 % of events is 4.7 months in arm A and 4.2 months in arm B. CONCLUSIONS Cetuximab can safely be added to the regimen of cisplatin and vinorelbine , with evidence suggesting enhancement of activity . No significant financial relationships to disclose BACKGROUND The phase III , r and omized , open-label ENSURE study ( NCT01342965 ) evaluated first-line erlotinib versus gemcitabine/cisplatin ( GP ) in patients from China , Malaysia and the Philippines with epidermal growth factor receptor ( EGFR ) mutation-positive non-small-cell lung cancer ( NSCLC ) . PATIENTS AND METHODS Patients ≥18 years old with histologically/cytologically confirmed stage IIIB/IV EGFR mutation-positive NSCLC and Eastern Cooperative Oncology Group performance status 0 - 2 were r and omized 1:1 to receive erlotinib ( oral ; 150 mg once daily until progression/unacceptable toxicity ) or GP [ G 1250 mg/m(2 ) i.v . days 1 and 8 ( 3-weekly cycle ) ; P 75 mg/m(2 ) i.v . day 1 , ( 3-weekly cycle ) for up to four cycles ] . Primary end point : investigator-assessed progression-free survival ( PFS ) . Other end points include objective response rate ( ORR ) , overall survival ( OS ) , and safety . RESULTS A total of 217 patients were r and omized : 110 to erlotinib and 107 to GP . Investigator-assessed median PFS was 11.0 months versus 5.5 months , erlotinib versus GP , respectively [ hazard ratio ( HR ) , 0.34 , 95 % confidence interval ( CI ) 0.22 - 0.51 ; log-rank P < 0.0001 ] . Independent Review Committee-assessed median PFS was consistent ( HR , 0.42 ) . Median OS was 26.3 versus 25.5 months , erlotinib versus GP , respectively ( HR , 0.91 , 95 % CI 0.63 - 1.31 ; log-rank P = .607 ) . ORR was 62.7 % for erlotinib and 33.6 % for GP . Treatment-related serious adverse events ( AEs ) occurred in 2.7 % versus 10.6 % of erlotinib and GP patients , respectively . The most common grade ≥3 AEs were rash ( 6.4 % ) with erlotinib , and neutropenia ( 25.0 % ) , leukopenia ( 14.4 % ) , and anemia ( 12.5 % ) with GP . CONCLUSION These analyses demonstrate that first-line erlotinib provides a statistically significant improvement in PFS versus GP in Asian patients with EGFR mutation-positive NSCLC ( NCT01342965 ) BACKGROUND The OPTIMAL study found that erlotinib improved progression-free survival ( PFS ) versus st and ard chemotherapy in Chinese patients with advanced EGFR mutation-positive non-small-cell lung cancer ( NSCLC ) . This report describes the quality of life ( QoL ) and up date d PFS analyses from this study . PATIENTS AND METHODS Chinese patients ≥ 18 years with histologically confirmed stage IIIB or IV NSCLC and a confirmed activating mutation of EGFR ( exon 19 deletion or exon 21 L858R point mutation ) received erlotinib ( 150 mg/day ; n = 82 ) or gemcitabine-carboplatin ( n = 72 ) . The primary efficacy end point was PFS ; QoL was assessed using the Functional Assessment of Cancer Therapy-Lung ( FACT-L ) question naire , Trial Outcome Index ( TOI ) and Lung Cancer Subscale ( LCS ) . RESULTS Patients receiving erlotinib experienced clinical ly relevant improvements in QoL compared with the chemotherapy group in total FACT-L , TOI and LCS ( P < 0.0001 for all scales ) . Erlotinib scored better than chemotherapy for all FACT-L subscales from baseline to cycles 2 and 4 ( non-significant ) . In the up date d analysis , PFS was significantly longer for erlotinib than chemotherapy ( median PFS 13.7 versus 4.6 months ; HR = 0.164 , 95 % CI = 0.105 - 0.256 ; P < 0.0001 ) , which was similar to the previously reported primary analysis . CONCLUSION Erlotinib  improves QoL compared with st and ard chemotherapy in the first-line treatment of patients with EGFR mutation-positive advanced NSCLC AIM This analysis investigates incidence and time course of rash in the EURTAC study . MATERIAL S & METHODS Patients with EGFR mutation-positive non-small-cell lung cancer were r and omized 1:1 to receive once daily erlotinib or 3-weekly cycles of chemotherapy . RESULTS Of the 86 erlotinib-treated patients , 71 reported rash . Median time to first rash appearance was 0.7 months . Most patients ( n = 65 ) had the same or lower grade rash at final assessment compared with initial assessment . Of the 21 patients with decreased rash grade between initial and final assessment s , 61.9 % received no erlotinib dose modification , 42.8 % had no concomitant rash treatment . CONCLUSION Most rash cases were mild , occurred within 1 month of erlotinib treatment , and rapidly improved without the need for erlotinib dose alterations BACKGROUND Previous , uncontrolled studies have suggested that first-line treatment with gefitinib would be efficacious in selected patients with non-small-cell lung cancer . METHODS In this phase 3 , open-label study , we r and omly assigned previously untreated patients in East Asia who had advanced pulmonary adenocarcinoma and who were nonsmokers or former light smokers to receive gefitinib ( 250 mg per day ) ( 609 patients ) or carboplatin ( at a dose calculated to produce an area under the curve of 5 or 6 mg per milliliter per minute ) plus paclitaxel ( 200 mg per square meter of body-surface area ) ( 608 patients ) . The primary end point was progression-free survival . RESULTS The 12-month rates of progression-free survival were 24.9 % with gefitinib and 6.7 % with carboplatin-paclitaxel . The study met its 
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Myelosuppression was consistently worse in the chemotherapy arms , fatigue and anorexia were also associated with some chemotherapies .
AUTHORS ' CONCLUSIONS Erlotinib , gefitinib , and afatinib are all active agents in EGFR M+ NSCLC patients , and demonstrate an increased tumour response rate and prolonged progression-free survival compared to cytotoxic chemotherapy .
We also found a beneficial effect of the TKI compared to cytotoxic chemotherapy .
However , we found no increase in overall survival for the TKI when compared with st and ard chemotherapy .
Cytotoxic chemotherapy is less effective in EGFR M+ NSCLC than erlotinib , gefitinib , or afatinib and is associated with greater toxicity .
There were no data supporting the use of monoclonal antibody therapy