***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 Previous , uncontrolled studies have suggested that first-line treatment with gefitinib would be efficacious in selected patients with non-small-cell lung cancer . METHODS In this phase 3 , open-label study , we r and omly assigned previously untreated patients in East Asia who had advanced pulmonary adenocarcinoma and who were nonsmokers or former light smokers to receive gefitinib ( 250 mg per day ) ( 609 patients ) or carboplatin ( at a dose calculated to produce an area under the curve of 5 or 6 mg per milliliter per minute ) plus paclitaxel ( 200 mg per square meter of body-surface area ) ( 608 patients ) . The primary end point was progression-free survival . RESULTS The 12-month rates of progression-free survival were 24.9 % with gefitinib and 6.7 % with carboplatin-paclitaxel . The study met its primary objective of showing the noninferiority of gefitinib and also showed its superiority , as compared with carboplatin-paclitaxel , with respect to progression-free survival in the intention-to-treat population ( hazard ratio for progression or death , 0.74 ; 95 % confidence interval [ CI ] , 0.65 to 0.85 ; P<0.001 ) . In the subgroup of 261 patients who were positive for the epidermal growth factor receptor gene ( EGFR ) mutation , progression-free survival was significantly longer among those who received gefitinib than among those who received carboplatin-paclitaxel ( hazard ratio for progression or death , 0.48 ; 95 % CI , 0.36 to 0.64 ; P<0.001 ) , whereas in the subgroup of 176 patients who were negative for the mutation , progression-free survival was significantly longer among those who received carboplatin-paclitaxel ( hazard ratio for progression or death with gefitinib , 2.85 ; 95 % CI , 2.05 to 3.98 ; P<0.001 ) . The most common adverse events were rash or acne ( in 66.2 % of patients ) and diarrhea ( 46.6 % ) in the gefitinib group and neurotoxic effects ( 69.9 % ) , neutropenia ( 67.1 % ) , and alopecia ( 58.4 % ) in the carboplatin-paclitaxel group . CONCLUSIONS Gefitinib is superior to carboplatin-paclitaxel as an initial treatment for pulmonary adenocarcinoma among nonsmokers or former light smokers in East Asia . The presence in the tumor of a mutation of the EGFR gene is a strong predictor of a better outcome with gefitinib . ( Clinical Trials.gov number , NCT00322452 . Introduction Osimertinib is an oral , central nervous system – active , EGFR tyrosine kinase inhibitor ( TKI ) for the treatment of EGFR T790M – positive advanced NSCLC . Here we have evaluated EGFR mutation frequencies in two phase II studies of osimertinib ( AURA extension and AURA2 ) . Methods After progression while receiving their latest line of therapy , patients with EGFR mutation – positive advanced NSCLC provided tumor sample s for m and atory central T790 M testing for the study selection criteria . Tumor tissue mutation analysis for patient selection was performed with the Roche cobas EGFR Mutation Test ( European Conformity – in vitro diagnostic , labeled investigational use only ) ( Roche Molecular Systems , Pleasanton , CA ) . Patients should not have been prescreened for T790 M mutation status . The cobas test results were compared with those of the MiSeq next‐generation sequencing system ( Illumina , San Diego , CA ) , which was used as a reference method . Results Sample s from 324 and 373 patients screened for AURA extension and AURA2 , respectively , produced valid cobas test results . The T790 M detection rates were similar between AURA extension and AURA2 ( 64 % and 63 % , respectively ) . The pooled T790 M rate was 63 % , with no difference by ethnicity ( 63 % for Asian and non‐Asian patients alike ) or immediately prior treatment with an EGFR TKI ( afatinib , 69 % ; erlotinib , 69 % ; and gefitinib , 63 % ) . A higher proportion of patients had T790 M detected against a background of exon 19 deletions versus L858R mutation ( 73 % versus 58 % [ p = 0.0002 ] ) . In both trials the cobas test demonstrated high sensitivity ( positive percent agreement ) and specificity ( negative percent agreement ) for T790 M detection when compared with the next‐generation sequencing reference method : positive percent agreement of 91 % versus 89 % and negative percent agreement of 97 % versus 98 % . Conclusions In both trials , the rate of detection of T790 M mutation in patients with advanced NSCLC was approximately 63 % and was unaffected by immediately prior treatment with an EGFR TKI or ethnicity Purpose : The exp and ing number of targeted therapeutics for non – small cell lung cancer ( NSCLC ) necessitates real-time tumor genotyping , yet tissue biopsies are difficult to perform serially and often yield inadequate DNA for next-generation sequencing ( NGS ) . We evaluated the feasibility of using cell-free circulating tumor DNA ( ctDNA ) NGS as a complement or alternative to tissue NGS . Experimental Design : A total of 112 plasma sample s obtained from a consecutive study of 102 prospect ively enrolled patients with advanced NSCLC were subjected to ultra-deep sequencing of up to 70 genes and matched with tissue sample s , when possible . Results : We detected 275 alterations in 45 genes , and at least one alteration in the ctDNA for 86 of 102 patients ( 84 % ) , with EGFR variants being most common . ctDNA NGS detected 50 driver and 12 resistance mutations , and mutations in 22 additional genes for which experimental therapies , including clinical trials , are available . Although ctDNA NGS was completed for 102 consecutive patients , tissue sequencing was only successful for 50 patients ( 49 % ) . Actionable EGFR mutations were detected in 24 tissue and 19 ctDNA sample s , yielding concordance of 79 % , with a shorter time interval between tissue and blood collection associated with increased concordance ( P = 0.038 ) . ctDNA sequencing identified eight patients harboring a resistance mutation who developed progressive disease while on targeted therapy , and for whom tissue sequencing was not possible . Conclusions : Therapeutically targetable driver and resistance mutations can be detected by ctDNA NGS , even when tissue is unavailable , thus allowing more accurate diagnosis , improved patient management , and serial sampling to monitor disease progression and clonal evolution . Clin Cancer Res ; 22(23 ) ; 5772–82 . © 2016 AACR Purpose : The evaluation of plasma testing for the  EGFR resistance mutation T790 M in NSCLC patients has not been broadly explored . We investigated the detection of EGFR activating and T790 M mutations in matched tumor tissue and plasma , mostly from patients with acquired resistance to first-generation EGFR inhibitors . Experimental Design : Sample s were obtained from two studies , an observational study and a phase I trial of rociletinib , a mutant-selective inhibitor of EGFR that targets both activating mutations and T790 M . Plasma testing was performed with the cobas EGFR plasma test and BEAMing . Results : The positive percent agreement ( PPA ) between cobas plasma and tumor results was 73 % ( 55/75 ) for activating mutations and 64 % ( 21/33 ) for T790 M . The PPA between BEAMing plasma and tumor results was 82 % ( 49/60 ) for activating mutations and 73 % ( 33/45 ) for T790 M . Presence of extrathoracic ( M1b ) versus intrathoracic ( M1a/M0 ) disease was found to be strongly associated with ability to identify EGFR mutations in plasma ( P < 0.001 ) . Rociletinib objective response rates ( ORR ) were 52 % [ 95 % confidence interval ( CI ) , 31 – 74 % ] for cobas tumor T790M-positive and 44 % ( 95 % CI , 25 – 63 % ) for BEAMing plasma T790M-positive patients . A drop in plasma-mutant EGFR levels to ≤10 molecules/mL was seen by day 21 of treatment in 7 of 8 patients with documented partial response . Conclusions : These findings suggest the cobas and BEAMing plasma tests can be useful tools for noninvasive assessment and monitoring of the T790 M resistance mutation in NSCLC , and could complement tumor testing by identifying T790 M mutations missed because of tumor heterogeneity or biopsy inadequacy . Clin Cancer Res ; 22(10 ) ; 2386–95 . © 2016 AACR BACKGROUND Activating mutations in EGFR are important markers of response to tyrosine kinase inhibitor ( TKI ) therapy in non-small-cell lung cancer ( NSCLC ) . The OPTIMAL study compared efficacy and tolerability of the TKI erlotinib versus st and ard chemotherapy in the first-line treatment of patients with advanced EGFR mutation-positive NSCLC . METHODS We undertook an open-label , r and omised , phase 3 trial at 22 centres in China . Patients older than 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 either oral erlotinib ( 150 mg/day ) until disease progression or unacceptable toxic effects , or up to four cycles of gemcitabine plus carboplatin . Patients were r and omly assigned ( 1:1 ) with a minimisation procedure and were stratified according to EGFR mutation type , histological subtype ( adenocarcinoma vs non-adenocarcinoma ) , and smoking status . The primary outcome was progression-free survival , analysed in patients with confirmed disease who received at least one dose of study treatment . The trial is registered at Clinical Trials.gov , number NCT00874419 , and has completed enrolment ; patients are still in follow-up . FINDINGS 83 patients were r and omly assigned to receive erlotinib and 82 to receive gemcitabine plus carboplatin ; 82 in the erlotinib  group and 72 in the  chemotherapy group were included in analysis of the primary endpoint . Median progression-free survival was significantly longer in erlotinib-treated patients than in those on chemotherapy ( 13.1 [ 95 % CI 10.58 - 16.53 ] vs 4.6 [ 4.21 - 5.42 ] months ; hazard ratio 0.16 , 95 % CI 0.10 - 0.26 ; p<0.0001 ) . Chemotherapy was associated with more grade 3 or 4 toxic effects than was erlotinib ( including neutropenia in 30 [ 42 % ] of 72 patients and thrombocytopenia in 29 [ 40 % ] patients on chemotherapy vs no patients with either event on erlotinib ) ; the most common grade 3 or 4 toxic effects with erlotinib were increased alanine aminotransferase concentrations ( three [ 4 % ] of 83 patients ) and skin rash ( two [ 2 % ] patients ) . Chemotherapy was also associated with increased treatment-related serious adverse events ( ten [ 14 % ] of 72 patients [ decreased platelet count , n=8 ; decreased neutrophil count , n=1 ; hepatic dysfunction , n=1 ] vs two [ 2 % ] of 83 patients [ both hepatic dysfunction ] ) . INTERPRETATION Compared with st and ard chemotherapy , erlotinib conferred a significant progression-free survival benefit in patients with advanced EGFR mutation-positive NSCLC and was associated with more favourable tolerability . These findings suggest that erlotinib is important for first-line treatment of patients with advanced EGFR mutation-positive NSCLC . FUNDING F Hoffmann-La Roche Ltd ( China ) ; Science and Technology Commission of Shanghai Municipality Purpose : The T790 M gatekeeper mutation in the EGFR is acquired by some EGFR-mutant non – small cell lung cancers ( NSCLC ) as they become resistant to selective tyrosine kinase inhibitors ( TKI ) . As third-generation EGFR TKIs that overcome T790M-associated resistance become available , noninvasive approaches to T790 M detection will become critical to guide management . Experimental Design : As part of a multi-institutional St and -Up-To-Cancer collaboration , we performed an exploratory analysis of 40 patients with EGFR-mutant tumors progressing on EGFR TKI therapy .  We compared the T790 M genotype from tumor biopsies with analysis of simultaneously collected circulating tumor cells ( CTC ) and circulating tumor DNA ( ctDNA ) . Results : T790 M genotypes were successfully obtained in 30 ( 75 
    Output:
    
The ctDNA analysis represents a promising , non-invasive approach to detect and monitor the T790 M mutation status  in NSCLC patients .