***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 ) 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 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 The irreversible epidermal growth factor receptor ( EGFR ) inhibitors have demonstrated efficacy in NSCLC patients with activating EGFR mutations , but it is unknown if they are superior to the reversible inhibitors . Dacomitinib is an oral , small-molecule irreversible inhibitor of all enzymatically active HER family tyrosine kinases . METHODS The ARCHER 1009 ( NCT01360554 ) and A7471028 ( NCT00769067 ) studies r and omized patients with locally advanced/metastatic NSCLC following progression with one or two prior chemotherapy regimens to dacomitinib or erlotinib .  EGFR mutation testing was performed central ly on archived tumor sample s. We pooled patients with exon 19 deletion and L858R EGFR mutations from both studies to compare the efficacy of dacomitinib to erlotinib . RESULTS One hundred twenty-one patients with any EGFR mutation were enrolled ; 101 had activating mutations in exon 19 or 21 . For patients with exon19/21 mutations , the median progression-free survival was 14.6 months [ 95 % confidence interval ( CI ) 9.0 - 18.2 ] with dacomitinib and 9.6 months ( 95 % CI 7.4 - 12.7 ) with erlotinib [ unstratified hazard ratio ( HR ) 0.717 ( 95 % CI 0.458 - 1.124 ) , two-sided log-rank , P = 0.146 ] . The median survival was 26.6 months ( 95 % CI 21.6 - 41.5 ) with dacomitinib versus 23.2 months ( 95 % CI 16.0 - 31.8 ) with erlotinib [ unstratified HR 0.737 ( 95 % CI 0.431 - 1.259 ) , two-sided log-rank , P = 0.265 ] . Dacomitinib was associated with a higher incidence of diarrhea and mucositis in both studies compared with erlotinib . CONCLUSIONS Dacomitinib is an active agent with comparable efficacy to erlotinib in the EGFR mutated patients . The subgroup with exon 19 deletion had favorable outcomes with dacomitinib . An ongoing phase III study will compare dacomitinib to gefitinib in first-line therapy of patients with NSCLC harboring common activating EGFR mutations ( ARCHER 1050 ; NCT01774721 ) . CLINICAL TRIALS NUMBER ARCHER 1009 ( NCT01360554 ) and A7471028 ( NCT00769067 ) Background There are well-known differences in gender outcome in non-small cell lung cancer ( NSCLC ) and other cancers . In this work , we evaluated several r and omised clinical trials to explore the gender influence in the outcome of patients with NSCLC treated with targeted therapy and immunotherapy .  Methods We performed a series of meta- analysis to compare the gender outcome in the routine setting for overall survival and progression-free survival ( PFS ) in phase III r and omised clinical trials comparing EGFR inhibitors versus chemotherapy ( OPTIMAL , LUX-lung 3 , LUX-lung 6 , EURTAC , ENSURE and WTJOG ) ; ALK inhibitors versus chemotherapy ( ASCEND 4 , ASCEND 5 , PROFILE 1014 and NCT009323893 ) and anti-PD1 checkpoint inhibitors versus chemotherapy ( CheckMate 017 , CheckMate 026 , CheckMate 057 , KEYNOTE 010 and KEYNOTE 024 ) . Results Female patients with NSCLC have a reduced risk of death compared with men ( HR=0.73 ; 95 % CI 0.67 to 0.79 ; p<0.00001 ) . Women had a better benefit from EGFR inhibitors than men ( HR=0.34 ; 95 % CI 0.28 to 0.40 ; p<0.00001 vs HR=0.44 ; 95 % CI 0.34 to 0.56 ; p<0.00001 , respectively ) . The benefit from ALK inhibitors was similar for both genders ( HR=0.51 ; 95 % CI 0.42 to 0.61 ; p<0.00001 vs HR=0.48 ; 95 % CI 0.39 to 0.59 ; p<0.00001 , for women and men , respectively ) . Anti-PD1 inhibitors significantly improved the PFS in male patients when compared with chemotherapy ( HR=0.76 ; 95 % CI 0.68 to 0.86 ; p<0.0000 
    Output:
    
Male patients , smokers and patients with EGFR exon 21 L858R mutation may derive less benefit from EGFR-TKIs compared to female patients , non-smokers and patients with EGFR exon 19 deletion