***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 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 ) Introduction In r and omly assigned studies with EGFR TKI only a minor proportion of patients with NSCLC have genetically profiled biopsies . Guidelines provide evidence to perform EGFR and KRAS mutation analysis in non-squamous NSCLC . We explored tumor biopsy quality offered for mutation testing , different mutations distribution , and outcome with EGFR TKI . Patient and Methods Clinical data from 8 regional hospitals were studied for patient and tumor characteristics , treatment and overall survival .  Biopsies sent to the central laboratory were evaluated for DNA quality and subsequently analyzed for mutations in exons 18–21 of EGFR and exon 2 of KRAS by bidirectional sequence analysis . Results Tumors from 442 subsequent patients were analyzed . For 74 patients ( 17 % ) tumors were unsuitable for mutation analysis . Thirty-eight patients ( 10.9 % ) had EGFR mutations with 79 % known activating mutations . One hundred eight patients ( 30 % ) had functional KRAS mutations . The mutation spectrum was comparable to the Cosmic data base . Following treatment in the first or second line with EGFR TKI  median overall survival for patients with EGFR ( n = 14 ) , KRAS ( n = 14 ) mutations and wild type EGFR/KRAS ( n = 31 ) was not reached , 20 and 9 months , respectively . Conclusion One out of every 6 tumor sample s was inadequate for mutation analysis . Patients with EGFR activating mutations treated with EGFR-TKI  have the longest survival 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 Background : A phase III trial was conducted to compare the safety and efficacy of erlotinib with that of gefitinib in advanced non-small cell lung cancer harbouring epidermal growth factor receptor mutations in exon 19 or 21 . Methods : Eligible patients were r and omised to receive erlotinib ( 150 mg per day ) or gefitinib ( 250 mg per day ) orally until disease progression or unacceptable toxicity . We aim ed to determine whether erlotinib is superior to gefitinib in efficacy . The primary end point was progression-free survival . Results : A total of 256 patients were r and omised to receive erlotinib ( N=128 ) or gefitinib ( N=128 ) . Median progression-free survival was not better with erlotinib than with gefitinib ( 13.0 vs 10.4 months , 95 % confidence interval ( CI ) 0.62–1.05 , P=0.108 ) . The corresponding response rates and median overall survival were 56.3 % vs 52.3 % ( P=0.530 ) and 22.9 vs 20.1 months ( 95 % CI 0.63–1.13 , P=0.250 ) , respectively . There were no significant differences in grade 3/4 toxicities between the two arms ( P=0.172 ) . Conclusions : The primary end point was not met . Erlotinib was not significantly superior to gefitinib in terms of efficacy in advanced non-small cell lung cancer with epidermal growth factor receptor mutations in exon 19 or 21 , and the two treatments had similar toxicities BACKGROUND The OPTIMAL study was the first study to compare efficacy and tolerability of the epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor ( TKI ) erlotinib , versus st and ard chemotherapy in first-line treatment of patients with EGFR mutation-positive advanced non-small-cell lung cancer ( NSCLC ) . Findings from final overall survival ( OS ) analysis and assessment of post- study treatment impact are presented . PATIENTS AND METHODS Of 165 r and omised patients , 82 received erlotinib and 72 gemcitabine plus carboplatin . Final OS analyses were conducted when 70 % of deaths had occurred in the intent-to-treat population . Subgroup OS was analysed by Cox proportional hazards model and included r and omisation stratification factors and post- study treatments . RESULTS Median OS was similar between the erlotinib ( 22.8 months ) and chemotherapy ( 27.2 months ) arms with no significant between-group differences in the overall population [ hazard ratio ( HR ) , 1.19 ; 95 % confidence interval ( CI ) 0.83 - 1.71 ; P = 0.2663 ] , the exon 19 deletion sub population ( HR , 1.52 ; 95 % CI 0.91 - 2.52 ; P = 0.1037 ) or the exon 21 L858 mutation sub population ( HR , 0.92 ; 95 % CI 0.55 - 1.54 ; P = 0.7392 ) . More patients in the erlotinib arm versus the chemotherapy arm did not receive any post- study treatment ( 36.6 % versus 22.2 % ) . Patients who received sequential combination of EGFR-TKI and chemotherapy had significantly improved OS compared with those who received EGFR-TKI or chemotherapy only ( 29.7 versus 20.7 or 11.2 months , respectively ; P < 0.0001 ) . OS was significantly shorter in patients who did not receive post- study treatments compared with those who received subsequent treatments in both arms . CONCLUSION The significant OS benefit observed in patients treated with EGFR-TKI  emphasises its contribution to improving survival of EGFR mutant NSCLC patients , suggesting that erlotinib should be considered st and ard first-line treatment of EGFR mutant patients and EGFR-TKI treatment following first-line therapy also brings significant benefits to those patients . CLINICAL TRIALSGOV IDENTIFIER NCT00874419 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 BACKGROUND NEJ002 study , comparing gefitinib with carboplatin ( CBDCA ) and paclitaxel ( PTX ; Taxol ) as the first-line treatment for advanced non-small cell lung cancer ( NSCLC ) harboring an epidermal growth factor receptor ( EGFR ) mutation , previously reported superiority of gefitinib over CBDCA/PTX on progression-free survival ( PFS ) . Subsequent analysis was carried out mainly regarding overall survival ( OS ) . MATERIAL S AND METHODS For all 228 patients in NEJ002 , survival data were up date d in December , 2010 . Detailed information regarding subsequent chemotherapy after the protocol treatment was also assessed retrospectively and the impact of some key drugs on OS was evaluated . RESULTS The median survival time ( MST ) was 27.7 
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Rank probabilities showed that osimertinib had a potentially better efficacy in terms of PFS and OS compared to all other TKIs .
For ORR , afatinib and osimertinib showed a trend of superiority compared to the other four TKIs .
Furthermore , there was a high risk of diarrhea and rash for patients treated with afatinib or dacomitinib as well as a moderate risk for treatment with erlotinib , gefitinib , and osimertinib .
Conclusion Our study showed a favorable efficacy of osimertinib in terms of PFS and OS compared to all other EGFR-TKIs in patients with NSCLC harboring activating EGFR mutations .
Furthermore , gefitinib , erlotinib , and osimertinib were associated with fewer toxicities compared to the other TKIs .
Therefore , osimertinib is indicated as a preferable first-line TKI in patients with activating EGFR-mutated NSCLC