***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 Epidermal growth factor receptor tyrosine kinase inhibitors ( TKIs ) administered concurrently with chemotherapy did not improve outcome in non-small-cell lung cancer ( NSCLC ) . However , in pre clinical models and early phase noncomparative studies , pharmacodynamic separation of chemotherapy and TKIs did show a synergistic effect . PATIENTS AND METHODS A r and omized phase II study was carried out in patients with advanced NSCLC who had progressed on or following first-line chemotherapy . Erlotinib 150 mg daily ( monotherapy ) or erlotinib 150 mg during 15 days intercalated with four 21-day cycles docetaxel for squamous ( SQ ) or pemetrexed for nonsquamous ( NSQ ) patients was administered ( combination therapy ) . After completion of chemotherapy , erlotinib was continued daily . Primary end point was progression-free survival ( PFS ) . RESULTS Two hundred and thirty-one patients were r and omized , 115 in the monotherapy arm and 116 in the combination arm . The adjusted hazard ratio for PFS was 0.76 [ 95 % confidence interval ( CI ) 0.58 - 1.02 ; P = 0.06 ] , for overall survival ( OS ) 0.67 ( 95 % CI 0.49 - 0.91 ; P = 0.01 ) favoring the combination arm . This improvement was primarily observed in NSQ subgroup . Common Toxicity Criteria grade 3 + toxic effect occurred in 20 % versus 56 % , rash in 7 % versus 15 % and febrile neutropenia in 0 % versus 6 % in monotherapy and combination therapy , respectively . CONCLUSIONS PFS was not significantly different between the arms . OS was significantly improved in the combination arm , an effect restricted to NSQ histology . STUDY REGISTRATION NUMBER NCT00835471 Purpose : The ISTANA ( IRESSA as Second-line Therapy in Advanced NSCLC — KoreA ) study compared gefitinib with docetaxel in patients with advanced or metastatic non – small cell lung carcinoma ( NSCLC ) pretreated with platinum-based chemotherapy . Experimental Design : We conducted a multicenter , r and omized , open-label phase III trial of gefitinib ( 250 mg/d ) versus docetaxel ( 75 mg/m2 day 1 every 3 weeks ) in patients with advanced or metastatic NSCLC treated with one previous platinum-based chemotherapy . The primary endpoint was progression-free survival . Results : A total of 161 patients ( male , 62 % ; never smoker , 41 % ; adenocarcinoma , 68 % ) were enrolled .  Progression-free survival was longer for gefitinib compared with docetaxel ( hazard ratio , 0.729 ; 90 % confidence interval , 0.533 - 0.998 ; one-sided P = 0.0441 ) . Gefitinib significantly improved objective response rate ( 28.1 % versus 7.6 % ; two-sided P = 0.0007 ) . In the final analysis of overall survival , the hazard ratio was 0.870 ( 95 % confidence interval , 0.613 - 1.236 ; two-sided P = 0.4370 ) . No significant differences were seen in the quality of life or symptom improvement rates between the two treatment groups . Gefitinib was well tolerated , was consistent with previous data and disease , and had fewer serious adverse events and fewer Common Terminology Criteria for Adverse Events grade 3 or 4 adverse events than docetaxel . The incidence of interstitial lung disease – type events was 3.7 % ( n = 3 ) with gefitinib and 3.9 % ( n = 3 ) with docetaxel . Conclusions : The primary endpoint of progression-free survival was longer with gefitinib than docetaxel , and the secondary endpoints showed superior objective response rate , good tolerability , and similar quality of life improvement rates for gefitinib than docetaxel . Therefore , gefitinib is an important valid treatment option for second-line therapy for Korean NSCLC patients . Clin Cancer Res ; 16(4 ) ; PURPOSE V and etanib is a once-daily oral inhibitor of vascular endothelial growth factor receptor ( VEGFR ) and epidermal growth factor receptor ( EGFR ) signaling . In this two-part phase II study , the efficacy and safety of v and etanib was compared with that of gefitinib , an inhibitor of EGFR signaling . PATIENTS AND METHODS Patients ( N = 168 ) with locally advanced or metastatic ( stage IIIB/IV ) non-small-cell lung cancer ( NSCLC ) , after failure of first-line with or without second-line platinum-based chemotherapy  , received once-daily v and etanib 300 mg ( n = 83 ) or gefitinib 250 mg ( n = 85 ) until disease progression or evidence of toxicity ( part A ) . After a 4-week washout period , eligible patients had the option to switch to the alternative treatment ( part B ) . Progression-free survival ( PFS ) was the primary efficacy assessment in part A , which was design ed to have a higher than 75 % power to detect a 33 % prolongation of PFS at a one-sided significance level of .2 . RESULTS In part A , v and etanib  prolonged PFS compared with gefitinib ( hazard ratio = 0.69 ; 95 % CI , 0.50 to 0.96 ; one-sided P = .013 ) . Patients receiving v and etanib experienced adverse events that were manageable and generally consistent with inhibition of EGFR and VEGFR signaling , including diarrhea , rash , and hypertension . There were no unexpected safety findings with gefitinib . Overall survival , a secondary assessment , was not significantly different between patients initially r and omly assigned to either v and etanib or gefitinib . CONCLUSION The primary efficacy objective was achieved , with v and etanib demonstrating a significant prolongation of PFS versus gefitinib . V and etanib 300 mg/d is currently being evaluated as a monotherapy in two r and omized phase III studies in advanced NSCLC PURPOSE To evaluate the efficacy and tolerability of two doses of gefitinib ( Iressa [ ZD1839 ] ; AstraZeneca , Wilmington , DE ) , a novel epidermal growth factor receptor tyrosine kinase inhibitor , in patients with pretreated advanced non-small-cell lung cancer ( NSCLC ) . PATIENTS AND METHODS This was a r and omized , double-blind , parallel-group , multicenter phase II trial . Two hundred ten patients with advanced NSCLC who were previously treated with one or two chemotherapy regimens ( at least one containing platinum )  were r and omly assigned to receive either 250-mg or 500-mg oral doses of gefitinib once daily . RESULTS Efficacy was similar for the 250- and 500-mg/d groups . Objective tumor response rates were 18.4 % ( 95 % confidence interval [ CI ] , 11.5 to 27.3 ) and 19.0 % ( 95 % CI , 12.1 to 27.9 ) ; among evaluable patients , symptom improvement rates were 40.3 % ( 95 % CI , 28.5 to 53.0 ) and 37.0 % ( 95 % CI , 26.0 to 49.1 ) ; median progression-free survival times were 2.7 and 2.8 months ; and median overall survival times were 7.6 and 8.0 months , respectively . Symptom improvements were recorded for 69.2 % ( 250 mg/d ) and 85.7 % ( 500 mg/d ) of patients with a tumor response . Adverse events ( AEs ) at both dose levels were generally mild ( grade 1 or 2 ) and consisted mainly of skin reactions and diarrhea . Drug-related toxicities were more frequent in the higher-dose group . Withdrawal due to drug-related AEs was 1.9 % and 9.4 % for patients receiving gefitinib 250 and 500 mg/d , respectively . CONCLUSION Gefitinib showed clinical ly meaningful antitumor activity and provided symptom relief as second- and third-line treatment in these patients . At 250 mg/d , gefitinib had a favorable AE profile . Gefitinib 250 mg/d is an important , novel treatment option for patients with pretreated advanced NSCLC [ corrected BACKGROUND Bevacizumab and erlotinib target different tumour growth pathways with little overlap in their toxic-effect profiles . On the basis of promising results from a phase 1/2 trial assessing safety and activity of erlotinib plus bevacizumab for recurrent or refractory non-small-cell lung cancer ( NSCLC ) , we aim ed to assess efficacy and safety of this combination in a phase 3 trial . METHODS In our double-blind , placebo-controlled , r and omised phase 3 trial ( BeTa ) , we enrolled patients with recurrent or refractory NSCLC who presented to 177 study sites in 12 countries after failure of first-line treatment . Patients were r and omly allocated in a one-to-one ratio to receive erlotinib plus bevacizumab ( bevacizumab group ) or erlotinib plus placebo ( control group ) according to a computer-generated r and omisation sequence by use of an interactive voice response system . The primary endpoint was overall survival in all enrolled patients . Patients , study staff , and investigators were masked to treatment assignment . We assessed safety by calculation of incidence of adverse events and tissue was collected for biomarker analyses . This trial is registered with Clinical Trials.gov , number NCT00130728 . FINDINGS Overall survival did not differ between 317 controls and 319 patients in the bevacizumab group ( hazard ratio [ HR ] 0·97 , 95 % CI 0·80 - 1·18 , p=0·7583 ) . Median overall survival was 9·3 months ( IQR 4·1 - 21·6 ) for patients in the bevacizumab group compared with 9·2 months ( 3·8 - 20·2 ) for controls . Progression-free survival seemed to be longer in the bevacizumab group ( 3·4 months [ 1·4 - 8·4 ] ) than in the control group ( 1·7 months [ 1·3 - 4·1 ] ; HR 0·62 , 95 % CI 0·52 - 0·75 ) and objective response rate suggested some clinical activity of bevacizumab and erlotinib . However , these secondary endpoint differences could not be defined as significant because the study prespecified that the primary endpoint had to be significant before testing of secondary endpoints could be done , to control type I error rate . In the bevacizumab group , 130 ( 42 % ) of 313 patients with safety  data had a serious adverse event , compared with 114 ( 36 % ) controls . There were 20 ( 6 % ) grade 5 adverse events , including two arterial thromboembolic events , in the bevacizumab group , and 14 ( 4 % ) in the control group . INTERPRETATION Addition of bevacizumab to erlotinib does not improve survival in patients with recurrent or refractory NSCLC . FUNDING Genentech PURPOSE To confirm the promising phase II results of docetaxel monotherapy , this phase III trial was conducted of chemotherapy for patients with advanced non-small-cell lung cancer ( NSCLC ) who had previously failed platinum-containing chemotherapy . PATIENTS AND METHODS A total of 373 patients were r and omized to receive either docetaxel 100 mg/m(2 ) ( D100 ) or 75 mg/m(2 ) ( D75 ) versus a control regimen of vinorelbine or ifosfamide ( V/I ) . The three treatment groups were well-balanced for key patient characteristics . RESULTS Overall response rates were 10.8 % with D100 and 6.7 % with D75 , each significantly higher than the 0.8 % response with V/I ( P = .001 and P = .036 , respectively ) . Patients who received docetaxel had a longer time to progression ( P = .046 , by log-rank test ) and a greater progression-free survival at 26 weeks ( P = .005 , by chi(2 ) test ) . Although overall survival was not significantly different between the three groups , the 1-year survival was significantly greater with D75 than with the control treatment ( 32 % v 19 % ; P = .025 , by chi(2 ) test ) . Prior exposure to paclitaxel did not decrease the likelihood of response to docetaxel , nor did it impact survival . There was a trend toward greater efficacy in patients whose disease was platinum-resistant rather than platinum-refractory and in patients with performance status of 0 or 1 versus 2 . Toxicity was greatest with D100 , but the D75 arm was well-tolerated . CONCLUSION This first r and omized trial in this setting demonstrates that D75 every 3 weeks can offer clinical ly meaningful benefit to patients with advanced NSCLC whose disease has relapsed or progressed after platinum-based chemotherapy PURPOSE The purpose of this study was to determine whether the addition of the epid 
    Output:
    
There is high- quality evidence that an egfrtki is preferred over a platinum doublet as initial therapy for patients with an activating mutation of the EGFR gene .
The egfrtkis are associated with a higher likelihood of response , longer progression-free survival , and improved quality of life .
Meta- analysis of those data demonstrates similar progression-free and overall survival .
There is consequently no preferred sequence for second-line egfrtki or second-line chemotherapy .
No molecular marker could identify patients in whom a survival benefit was not observed ; however , the magnitude of the benefit was modest .