***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 
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    Input: Background Gefitinib , a tyrosine kinase inhibitor , is an effective treatment in advanced non-small cell lung cancer ( NSCLC ) patients with an activating mutation in the epidermal growth factor receptor ( EGFR ) . R and omised clinical trials showed a benefit in progression free survival for gefitinib versus doublet chemotherapy regimens in patients with an activated EGFR mutation ( EGFR M+ ) . From a patient perspective , progression free survival is important , but so is health-related quality of life . Therefore , this analysis evaluates the Quality Adjusted progression free survival of gefitinib versus three relevant doublet chemotherapies ( gemcitabine/cisplatin ( Gem/Cis ) ; pemetrexed/cisplatin ( Pem/Cis ) ; paclitaxel/carboplatin ( Pac/Carb ) ) in a Dutch health care setting in patients with EGFR M+ stage IIIB/IV NSCLC . This study uses progression free survival rather than overall survival for its time frame in order to better compare the treatments and to account for the influence that subsequent treatment lines would have on overall survival analysis . Methods Mean progression free survival for Pac/Carb was obtained by extrapolating the median progression free survival as reported in the Iressa-Pan-Asia Study ( IPASS ) . Data from a network meta- analysis was used to estimate the mean progression free survival for therapies of interest relative to Pac/Carb . Adjustment for health-related quality of life was done by incorporating utilities for the Dutch population , obtained by converting FACT-L data ( from IPASS ) to utility values and multiplying these with the mean progression free survival for each treatment arm to determine the Quality Adjusted progression free survival . Probabilistic sensitivity analysis was carried out to determine 95 % credibility intervals . Results The Quality Adjusted progression free survival ( PFS ) ( mean , ( 95 % credibility interval ) ) was 5.2 months ( 4.5 ; 5.8 ) for Gem/Cis , 5.3 months ( 4.6 ; 6.1 ) for Pem/Cis ; 4.9 months ( 4.4 ; 5.5 ) for Pac/Carb and 8.3 ( 7.0 ; 9.9 ) for gefitinib . Conclusions In the Dutch health care setting , the previously established progression free survival benefit of first-line gefitinib in advanced NSCLC EGFR M+ patients in comparison to st and ard doublet chemotherapy is further supported by the Quality Adjusted PFS , which takes into account the additional health-related quality of life benefits of gefitinib over doublet chemotherapy 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 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 ) ; BACKGROUND For non-small cell lung cancer ( NSCLC ) patients with epidermal growth factor receptor ( EGFR ) mutations , first-line gefitinib produced a longer progression-free survival interval than first-line carboplatin plus paclitaxel but did not show any survival advantage in the North East Japan 002 study . This report describes the quality of life ( QoL ) analysis of that study . METHODS  Chemotherapy-naïve patients with sensitive EGFR-mutated , advanced NSCLC were r and omized to receive gefitinib or chemotherapy ( carboplatin and paclitaxel ) .  Patient QoL was assessed weekly using the Care Notebook , and the primary endpoint of the QoL analysis was time to deterioration from baseline on each of the physical , mental , and life well-being QoL scales . Kaplan-Meier probability curves and log-rank tests were employed to clarify differences . RESULTS QoL data from 148 patients ( 72 in the gefitinib arm and 76 in the carboplatin plus paclitaxel arm ) were analyzed . Time to defined deterioration in physical and life well-being significantly favored gefitinib over chemotherapy ( hazard ratio [ HR ] of time to deterioration , 0.34 ; 95 % confidence interval [ CI ] , 0.23 - 0.50 ; p < .0001 and HR , 0.43 ; 95 % CI , 0.28 - 0.65 ; p < .0001 , respectively ) . CONCLUSION QoL was maintained much longer in patients treated with gefitinib than in patients treated with st and ard chemotherapy , indicating that gefitinib should be considered as the st and ard first-line therapy for advanced EGFR-mutated NSCLC in spite of no survival advantage Introduction : This post hoc analysis investigated the relationship between tumor response and overall survival ( OS ) in pretreated advanced non-small cell lung cancer ( NSCLC ) . Methods : We conducted l and mark survival analyses of V-15 - 32 , a phase III study comparing gefitinib with docetaxel in pretreated advanced NSCLC . Best response at weeks 8 , 12 , 16 , and 20 , and visit response at week 4 , were evaluated . Results : Disease control ( DC ; complete response [ CR ] , partial response [ PR ] , or stable disease ) was a better predictor of OS than CR/PR at all time points . The strongest predictor of OS for both gefitinib and docetaxel was DC at week 8 ( hazard ratio [ HR ] DC versus non-DC : 0.30 , 95 % confidence interval [ CI ] 0.20–0.45 , p < 0.001 for both treatments ) . DC at week 4 was also associated with longer survival compared with non-DC for both treatments ( HR 0.33 , 95 % CI 0.23–0.49 , p < 0.001 for gefitinib ; HR 0.30 , 95 % CI 0.19–0.47 , p < 0.001 for docetaxel ) . Discussion : DC is a better predictor of OS with gefitinib and docetaxel than CR/PR in advanced pretreated NSCLC , with a best response of DC at week 8 the strongest predictor 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 This study was design ed to evaluate the safety , pharmacokinetics , and clinical activity of pazopanib combined with paclitaxel to determine the recommended phase II dose in the first-line setting in patients with advanced solid tumors . Patients were enrolled in a 3 + 3 dose-escalation design to determine the maximum tolerated regimen ( MTR ) of once daily pazopanib plus paclitaxel administered every 3 weeks at four dose levels ( DL1 - 4 ) . Safety , pharmacokinetics , pharmacogenetics , and disease assessment s were performed . Twenty-eight patients received treatment . One patient at DL1 had dose-limiting toxicity ( DLT ) of elevated hepatic enzymes . After pazopanib discontinuation , liver enzyme concentrations remained high until a concurrent medication , simvastatin , was discontinued . This patient had the defective CYP2C8 * 3 * 3 genotype . At DL2 , 1 patient had DLT of elevated hepatic enzymes with rash and 1 patient had DLT of rash . The MTR was paclitaxel 150 mg/m2 plus pazopanib 800 mg . The most common 
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Finally , EGFR-TKIs were superior to taxanes in most of all grade s or grade ≥3 AEs .
Conclusion : In the efficacy and safety evaluation , EGFR-TKIs had an advantage in the treatment of NSCLC , especially for patients with EGFR mutation-positive .