***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: This study was design ed to prospect ively evaluate the efficacy and safety of first-line gefitinib treatment in patients with advanced pulmonary adenocarcinoma harboring epidermal growth factor receptor ( EGFR ) mutations and to explore the molecular factors affecting the efficacy of gefitinib . Tumor tissue , derived from either the original tumor or the metastatic or recurrent site was taken from chemo-naïve pts with advanced ( stage IIIB , IV , and recurrent ) pulmonary adenocarcinoma . Tumor genomic DNA underwent direct sequencing for EGFR exons 18 , 19 , 20 , and 21 . Patients with EGFR mutations received 250 mg of gefitinib daily until disease progression or unacceptable toxicity . The primary endpoint was objective response rate ( ORR ) . Secondary endpoints were progression free survival ( PFS ) , overall survival ( OS ) and tolerability .  Out of 147 screened patients , 45 pts ( 31 % ) had EGFR mutations and received  gefitinib . The most common EGFR mutations were in-frame exon 19 deletions ( 29 pts , 64 % ) and L858R point mutation in exon 21 ( 15 pts , 33 % ) . One patient had atypical mutation of L861Q in exon 21 . The ORR was 53.3 % ( 95 % CI , 38.6 - 67.9 ) and disease control rate ( DCR ) including stable disease was 86.7 % . The median progression free survival ( PFS ) was 398 days and the median overall survival ( OS ) was 819 days . Treatment was well tolerated . Grade 3/4 adverse events ( AEs ) were reported by 6 patients and treatment-related Grade 3 AEs by 3 patients . There were no treatment-related Grade 4 AEs . Exploratory subgroup analysis according to the EGFR mutation subtypes was carried out . The ORR and DCR were higher in patients with exon 19 deletions than those with L858R ( 62.1 % vs 33.3 % ; P=0.0705 and 96.6 % vs 66.7 % ; P=0.0062 , respectively ) . All 4 patients with progressive disease had a L858R mutation . No secondary resistant mutations such as T790 M mutation or insertions in exon 20 were found in those patients . In addition , OS was significantly better in patients with exon 19 deletions than those with L858R ( 24-month OS rate was 72.1 % vs 32.0 % , P=0.0148 ) . Gefitinib as the first-line treatment for Korean patients with advanced pulmonary adenocarcinoma harboring EGFR mutations was effective and well tolerated . Subgroup analysis suggests that the benefit from gefitinib treatment was more prominent in patients with the exon 19 deletion mutations ( Clinical Trials.gov number , NCT00344773 ) Purpose : The purpose of our study was to determine whether multidrug resistance proteins ( MRP ) are of prognostic and /or predictive value in patients who were enrolled into the International Adjuvant Lung Cancer Trial ( IALT ) . Experimental Design : Expression of MRP1 and MRP2 was immunohistochemically assessed in tumor specimens obtained from 782 IALT patients . Prognostic and predictive analyses were based on Cox models adjusted for clinical and pathologic variables . Results : MRP1 expression was considered positive in 364 ( 47 % ) patients and MRP2 expression in 313 ( 40 % ) patients . MRP2-positive patients had a significantly shorter overall survival than MRP2-negative patients in the total patient population [ adjusted hazard ratio for death , 1.37 ; 95 % confidence interval ( 95 % CI ) , 1.09 - 1.72 ; P = 0.007 ] . There was no significant association between MRP1 expression and overall survival . Neither MRP1 nor MRP2 predicted response to adjuvant cisplatin-based chemotherapy .  Conclusions : MRP2 expression is an independent prognostic factor in patients with completely resected non – small cell lung cancer but neither MRP1 nor MRP2 was of predictive value in patients enrolled into the IALT PURPOSE This study was undertaken to investigate the efficacy and the feasibility of gefitinib for chemotherapy-naïve patients with advanced non-small-cell lung cancer ( NSCLC ) harboring epidermal growth factor receptor ( EGFR ) mutations . PATIENTS AND METHODS The EGFR gene status in various tumor sample s obtained from chemotherapy-naïve advanced NSCLC patients was examined by DNA sequencing of EGFR exons 18 to 23 . Patients harboring EGFR mutations received gefitinib ( 250 mg/d ) alone . The response rate , progression-free survival ( PFS ) , and toxicity profile were assessed prospect ively . RESULTS Between June 2004 and October 2005 , 75 patients were examined for the EGFR status , and 25 patients ( 33 % ) harbored EGFR mutations .  EGFR mutations were significantly frequent in females ( P < .01 ) and never or light smokers ( P < .001 ) . Sixteen patients with EGFR mutations were enrolled onto the study . The overall response rate in these patients was 75 % ( 95 % CI , 54 % to 96 % ) , and the disease control rate was 88 % ( 95 % CI , 71 % to 100 % ) . The median PFS time of these patients was 9.7 months ( 95 % CI , 7.4 to 9.9 months ) . No life-threatening toxicity was observed . CONCLUSION Treatment with gefitinib alone for chemotherapy-naïve NSCLC patients with EGFR mutations could achieve a high efficacy with acceptable toxicity . To assess the proper timing of gefitinib in such patients , a subsequent r and omized trial comparing gefitinib with st and ard chemotherapy is warranted Introduction : PIONEER ( NCT01185314 ) was a prospect i ve , multinational , epidemiological study of epidermal growth factor receptor ( EGFR ) mutations in patients from Asia with newly diagnosed advanced lung adenocarcinoma . Methods : Eligible patients ( aged ≥20 years ) had untreated stage IIIB/IV adenocarcinoma . The EGFR mutation status ( primary end point : positive , negative , or undetermined ) of tumor sample s ( biopsy , surgical specimen , or cytology ) was determined ( Scorpion amplification refractory mutation system ) . EGFR mutation frequency was calculated and compared between demographic and clinical subgroups . Results : Of 1482 patients from seven Asian regions , 43.4 % of patients were female , median age was 60 years ( range , 17–94 ) , and 52.6 % of patients were never-smokers . EGFR mutation status was evaluable in tumors from 1450 patients ( 97.8 % ) ( 746 [ 51.4 % ] positive ; 704 [ 48.6 % ] negative ) . Country , sex , ethnicity , smoking status , pack-years ( all p < 0.001 ) , disease stage ( p = 0.009 ) , and histology type ( p = 0.016 ) correlated significantly with EGFR mutation frequency . Mutation frequency was 61.1 % in females , 44.0 % in males ; lower in patients from India ( 22.2 % ) compared with other areas ( 47.2%–64.2 % ) ; highest among never-smokers ( 60.7 % ) ; and decreased as pack-year number increased ( > 0–10 pack-years , 57.9 % ; > 50 pack-years , 31.4 % ) ( similar trend by sex ) . Ethnic group ( p < 0.001 ) and pack-years ( p < 0.001 ) had statistically significant associations with mutation frequency ( multivariate analysis ) ; sex was not significant when adjusted for smoking status . Conclusion : PIONEER is the first prospect i ve study to confirm high EGFR mutation frequency ( 51.4 % overall ) in tumors from Asian patients with adenocarcinoma . The observed high mutation frequency in demographic/ clinical subgroups compared with white population s suggests that mutation testing should be considered for all patients with stage IIIB/IV adenocarcinoma , even males and regular smokers , among Asian population The purpose of this study was to evaluate the efficacy of gefitinib and the feasibility of screening for epidermal growth factor receptor ( EGFR ) mutations among select patients with advanced non-small cell lung cancer ( NSCLC ) . Stage IIIB/IV NSCLC , chemotherapy-naive patients or patients with recurrences after up to two prior chemotherapy regimens were eligible .  Direct sequencing using DNA from tumour specimens was performed by a central laboratory to detect EGFR mutations . Patients harbouring EGFR mutations received gefitinib . The primary study objective was response ; the secondary objectives were toxicity , overall survival ( OS ) , progression-free survival ( PFS ) , 1-year survival ( 1Y-S ) and the disease control rate ( DCR ) .  Between March 2005 and January 2006 , 118 patients were recruited from 15 institutions and were screened for EGFR mutations , which were detected in 32 patients – 28 of whom were enrolled in the present study . The overall response rate was 75 % , the DCR was 96 % and the median PFS was 11.5 months . The median OS has not yet been reached , and the 1Y-S was 79 % . Thus , gefitinib chemotherapy in patients with advanced NSCLC harbouring EGFR mutations was highly effective . This trial documents the feasibility of performing a multicentre phase II study using a central typing laboratory , demonstrating the benefit to patients of selecting gefitinib treatment based on their EGFR mutation status PURPOSE Somatic mutations in the epidermal growth factor receptor ( EGFR ) correlate with increased response in patients with non-small-cell lung cancer ( NSCLC ) treated with EGFR tyrosine kinase inhibitors ( TKIs ) .  The multicenter iTARGET trial prospect ively examined first-line gefitinib in advanced NSCLC patients harboring EGFR mutations and explored the significance of EGFR mutation subtypes and TKI resistance mechanisms . PATIENTS AND METHODS  Chemotherapy-naïve patients with advanced NSCLC with > or= 1 clinical characteristic associated with EGFR mutations underwent direct DNA sequencing of tumor tissue EGFR exons 18 to 21 . Patients found to harbor any EGFR mutation were treated with gefitinib 250 mg/d until progression or unacceptable toxicity . The primary outcome was response rate . RESULTS Ninety-eight patients underwent EGFR screening and mutations were detected in 34 ( 35 % ) . EGFR mutations were primarily exon 19 deletions ( 53 % ) and L858R ( 26 % ) though 21 % of mutation-positive cases had less common subtypes including exon 20 insertions , T790M/L858R , G719A , and L861Q . Thirty-one patients received gefitinib .  The response rate was 55 % ( 95 % CI , 33 to 70 ) and median progression-free survival was 9.2 months ( 95 % CI , 6.2 to 11.8 ) . Therapy was well tolerated ; 13 % of patients had grade 3 toxicities including one grade 3 pneumonitis . Two patients with classic activating mutations exhibited de novo  gefitinib resistance and had concurrent genetic anomalies usually associated with acquired TKI resistance , specifically the T790 M EGFR mutation and MET amplification . CONCLUSION First-line therapy with gefitinib administered in a genotype-directed fashion to patients with advanced NSCLC harboring EGFR mutations results in very favorable clinical outcomes with good tolerance . This strategy should be compared with combination chemotherapy , the current st and ard of care 
    Output:
    
In conclusion , the findings from this study suggest that increase in MRP1 gene expression is associated with being a non‑smoker , adenocarcinoma , advanced clinical stages and a poor response to chemotherapy in patients with NSCLC .