***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: Purpose : Somatic mutations in the epidermal growth factor receptor ( EGFR ) have been detected in patients with non – small cell lung cancer ( NSCLC ) and are associated with sensitivity to treatment with gefitinib or erlotinib . Our study explored the relationship between the two most common types of somatic EGFR mutations , exon 19 deletions and the L858R point mutation , and outcomes of patients following treatment with gefitinib or erlotinib .  Experimental Design : Tumor specimens obtained before treatment with gefitinib or erlotinib were analyzed for EGFR mutations . Patients with exon 19 deletion or L858R mutations were identified . The response rate , time to progression , and overall survival were determined for the two groups . Results : We identified 36 patients with NSCLC and an EGFR mutation who were treated with gefitinib or erlotinib .  Patients with an exon 19 deletion had a significantly longer overall survival compared with patients with an L858R mutation ( 38 versus 17 months ; P = 0.04 ) . There were also trends toward higher response rate ( 73 % versus 50 % ) and improved time to progression ( 24 versus 10 months ) for the patients with an exon 19 deletion , although these were not independently significant in a multivariate analysis . A difference in response rate for patients treated with gefitinib compared with erlotinib was also noted [ 18 of 23 ( 78 % ) versus 3 of 9 ( 33 % ) ; P = 0.04 ] . No obvious difference in time to progression or overall survival was noted between gefitinib- and erlotinib-treated patients . Conclusions : Patients with NSCLC and EGFR exon 19 deletions have a longer survival following treatment with gefitinib or erlotinib compared with those with the L858R mutation . Pooling of greater numbers of patients and completion of prospect i ve trials are needed to further define the predictive and prognostic roles of different EGFR mutations with respect to treatment with gefitinib , erlotinib , and other EGFR inhibitors Background In Non-small cell lung cancer ( NSCLC ) , an overactive epidermal growth factor receptor ( EGFR ) pathway is a component of the malignant phenotype . Two tyrosine kinase inhibitors ( TKIs ) of EGFR , gefinitib and erlotinib , have been used with variable benefit . Methods We have analyzed outcome data of a population of NSCLC patients that received these TKIs  to determine the benefit derived and to define the clinical and molecular parameters that correlate with response . Tumor tissue from a subgroup of these patients was analyzed by immunohistochemistry to measure the expression level of EGFR and four activated ( phosphorylated ) members of the pathway , pEGFR , pERK , pAKT , and pSTAT3 . Results Erlotinib was slightly superior to gefitinib in all measures of response , although the differences were not statistically significant . The most robust clinical predictors of time to progression ( TTP ) were best response and rash ( p < 0.0001 ) . A higher level of pEGFR was associated with longer TTP , while the total EGFR level was not associated with response . Higher levels of pAKT and pSTAT3 were also associated with longer TTP . In contrast , a higher level of pERK1/2 was associated with shorter TTP . Conclusion These observations suggest the hypothesis that tumor cells that have activated EGFR pathways , presumably being utilized for survival , are clinical ly relevant targets for pathway inhibition . An accurate molecular predictive model of TKI response should include activated members of the EGFR pathway . TKIs may be best reserved for tumors expressing pEGFR and pAKT or pSTAT , and little pERK . In the absence of molecular predictors of response , the appearance of a rash and a positive first scan are good clinical indicators of response 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 compared with gefitinib , with a manageable tolerability profile . These data are potentially important for clinical decision making in this patient population . FUNDING Boehringer Ingelheim PURPOSE The epidermal growth factor receptor ( EGFR ) tyrosine kinase has been an important target for non-small-cell lung cancer . Several EGFR tyrosine kinase inhibitors ( TKIs ) are currently approved , and both gefitinib and erlotinib are the most well-known first-generation EGFR-TKIs . This r and omized phase III study was conducted to investigate the difference between these two EGFR-TKIs . PATIENTS AND METHODS Previously treated patients with lung adenocarcinoma were r and omly assigned to receive gefitinib or erlotinib . This study aim ed to investigate the noninferiority of gefitinib compared with erlotinib . The primary end point was progression-free survival ( PFS ) . RESULTS Five hundred sixty-one patients were r and omly assigned , including 401 patients ( 71.7 % ) with EGFR mutation . All baseline factors ( except performance status ) were balanced between the arms . Median PFS and overall survival times for gefitinib and erlotinib were 6.5 and 7.5 months ( hazard ratio [ HR ] , 1.125 ; 95 % CI , 0.940 to 1.347 ; P = .257 ) and 22.8 and 24.5 months ( HR , 1.038 ; 95 % CI , 0.833 to 1.294 ; P = .768 ) , respectively . The response rates for gefitinib and erlotinib were 45.9 % and 44.1 % , respectively . Median PFS times in EGFR mutation-positive patients receiving gefitinib versus erlotinib were 8.3 and 10.0 months , respectively ( HR , 1.093 ; 95 % CI , 0.879 to 1.358 ; P = .424 ) . The primary grade 3 or 4 toxicities were rash ( 2.2 % for gefitinib v 18.1 % for erlotinib ) and alanine aminotransferase (ALT)/aspartate aminotransferase ( AST ) elevation ( 6.1%/13.0 % for gefitinib v 2.2%/3.3 % for erlotinib ) . CONCLUSION The study did not demonstrate noninferiority of gefitinib compared with erlotinib in terms of PFS in patients with lung adenocarcinoma according to the predefined criteria BACKGROUND AND OBJECTIVE It has been proven that epidermal growth factor receptor-tyrosine kinase inhibitor ( EGFR-TKI ) significantly benefits advanced non-small cell lung cancer ( NSCLC ) patients harboring EGFR mutations in progression-free survival time with better tolerance . This study is undertaken to analyze efficacy and tolerance of advanced NSCLC patients harboring EGFR mutations taking EGFR-TKI as a first-line therapy . METHODS Tumor sample s from 54 patients with advanced NSCLC were examined for EGFR activating mutations ( deletion mutation in exon 19 and the L858R point mutation in exon 21 ) by direct sequencing  . The patients were first-line treated with oral administration of EGFR-TKI until disease progression . The efficacy and adverse events were observed , and survival was followed up . RESULTS Among the patients , 61 % ( 33 of 54 ) had EGFR exon 19 deletion , and 39 % ( 21 of 54 ) had EGFR L858R point mutation . All patients received first-line TKI therapy . The total response rate was 96 % , median progression free survival ( PFS ) was 8.3 months and median survival was 19.5 months . The patients with EGFR exon 19 deletion had significantly longer median PFS ( 9 versus 7 months , P=0.002 ) and longer median overall survival (OS)(25 versus 16 months , P=0.001 ) than patients with EGFR L858R point mutation . There is no significance in efficacy between gefitinib and erlotinib , and gefitinib is safer than erlotinib . The most common adverse events were rash and diarrhea . Two ( 4 % ) grade 4 skin toxity effects , two ( 4 % ) grade 3 aminotransferase level elevations , and one ( 1 ) grade 3 stomatitis were observed . CONCLUSION The first-line EGFR-TKI treatment in advanced NSCLC patients harboring EGFR mutations is efficient and safe , which is more efficient in patients with EGFR exon 19 deletion than those with EGFR L858R mutation Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more PURPOSE To establish the safety and tolerability of ZD1839 ( Iressa ) , a selective epidermal growth factor receptor ( EGFR ) tyrosine kinase inhibitor , and to explore its pharmacokinetic and pharmacodynamic effects in patients with selected solid tumor types . PATIENTS AND METHODS This was a phase I dose-escalating trial of oral ZD1839 150 mg/d to a maximum of 1,000 mg/d given once daily for at least 28 days . Patients with either advanced non-small-cell lung , ovarian , head and neck , prostate , or colorectal cancer were recruited . RESULTS Eighty-eight patients received ZD1839  ( 150 to 1,000 mg/d ) . At 1 
    Output:
    
No solid evidence was found that afatinib had greater efficacy than gefitinib or erlotinib in first-line treatment of EGFR-mutant NSCLC .
However , afatinib was more effective than erlotinib as second-line treatment of patients with advanced squamous cell carcinoma .
The grade 3/4 adverse events rate of afatinib was comparable to that of erlotinib but higher than that of gefitinib