***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 . Purpose : Patients with epidermal growth factor receptor (EGFR)-mutant lung adenocarcinoma develop acquired resistance to EGFR tyrosine kinase inhibitors ( TKI ) after a median of 10 to 16 months . In half of these cases , a second EGFR mutation , T790 M , underlies acquired resistance . We undertook this study to examine the clinical course of patients harboring the T790 M mutation following progression on TKI .  Experimental Design : EGFR-mutant lung cancer patients with acquired resistance to EGFR TKIs  were identified as part of a prospect i ve rebiopsy protocol in which postprogression tumor specimens were collected for molecular analysis . Postprogression survival and characteristics of disease progression were compared in patients with and without T790 M . Results : We identified T790 M in the initial rebiopsy specimens from 58 of 93 patients ( 62 % , 95 % CI : 52–72 ) . T790 M was more common in biopsies of lung/pleura tissue and lymph nodes than in more distant sites ( P = 0.014 ) . Median postprogression survival was 16 months ( interquartile range = 9–29 months ) ; patients with T790 M had a significantly longer postprogression survival ( P = 0.036 ) . Patients without T790 M more often progressed in a previously uninvolved organ system ( P = 0.014 ) and exhibited a poorer performance status at time of progression ( P = 0.007 ) . Conclusions : Among patients with acquired resistance to EGFR TKIs , the presence of T790 M defines a clinical subset with a relatively favorable prognosis and more indolent progression . Knowledge of T790 M status is therefore important both for the clinical care of these patients and for the optimal design and interpretation of clinical trials in this setting . Clin Cancer Res ; 17(6 ) ; 1616–22 . © 2010 AACR Purpose : Whether bevacizumab enhances the effect of the epidermal growth factor receptor ( EGFR ) inhibitor gefitinib on EGFR mutant non – small cell lung cancers ( NSCLCs ) remains unknown . We conducted a phase II trial to investigate the efficacy and safety of gefitinib when combined with bevacizumab as first-line therapy in patients with advanced NSCLC harboring EGFR gene mutations . Methods : In this trial , 42 patients with a performance status of 0 to 2 received gefitinib ( 250 mg/d ) and bevacizumab ( 15 mg/kg , every 3 weeks ) . The primary end point of this study was the 1-year progression-free survival ( PFS ) rate . We assumed that a 1-year PFS rate of 55 % would indicate potential usefulness and that a 1-year PFS rate of 40 % would constitute the lower limit of interest . Results : Forty-two patients were enrolled in the study with a median age of 73 ( range 42–86 ) years . Activating EGFR gene mutations included exon 19 deletion ( 57 % ) and L858R point mutations in exon 21 ( 38 % ) . The objective response rate was 73.8 % and included two complete responses . The 1-year PFS rate and median PFS time were 56.7 % ( 95 % confidence interval [ CI ] 39.9–70.5 ) and 14.4 months ( 95 % CI 10.1–19.2 ) , respectively . The median PFS differed significantly between EGFR exon 19 deletion and the L858R point mutation ( 18.0 versus 9.4 months , respectively ; p = 0.006 ) . The median overall survival had not yet been reached . Severe adverse events included grade 3 skin rash ( 15 % ) , hypertension ( 17 % ) , aspartate transaminase/alanine aminotransferase elevation ( 17 % ) , proteinuria ( 7 % ) , intracranial hemorrhage ( 2 % ) , and grade 4 perforation of the digestive tract ( 2 % ) . There were no treatment-related deaths . Conclusion : Gefitinib in combination with bevacizumab as first-line therapy seems to be a favorable and well-tolerated treatment for patients with advanced NSCLC with activating EGFR gene mutations , especially those with EGFR exon 19 deletion mutations , although the primary end point was not met because the lower limit of the CI was less than 40 % 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 months for the gefitinib group , and was 26.6 months for the CBDCA/PTX group ( HR , 0.887 ; P=0.483 ) . The OS of patients who received platinum throughout their treatment ( n=186 ) was not statistically different from that of patients who never received platinum ( n=40 ) . The MST of patients treated with gefitinib , platinum , and pemetrexed ( PEM ) or docetaxel ( DOC , Taxotere ; n=76 ) was around 3 years . CONCLUSIONS No significant difference in OS was observed between gefitinib and CBDCA/PTX in the NEJ002 study , probably due to a high crossover use of gefitinib in the CBDCA/PTX group . Considering the many benefits and the risk of missing an opportunity to use the most effective agent for EGFR-mutated NSCLC , the first-line gefitinib is strongly recommended 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 BACKGROUND Non-small-cell lung cancer with sensitive mutations of the epidermal growth factor receptor ( EGFR ) is highly responsive to EGFR tyrosine kinase inhibitors such as gefitinib , but little is known about how its efficacy and safety profile compares with that of st and ard chemotherapy . METHODS We r and omly assigned 230 patients with metastatic , non-small-cell lung cancer and EGFR mutations who had not previously received chemotherapy to receive gefitinib or carboplatin-paclitaxel .  The primary end point was progression-free survival ; secondary end points included overall survival , response rate , and toxic effects . RESULTS In the planned interim analysis of data for the first 200 patients , progression-free survival was significantly longer in the gefitinib group than in the st and ard-chemotherapy group ( hazard ratio for death or disease progression with gefitinib , 0.36 ; P<0.001 ) , result ing in early termination of the study . The gefitinib group had a significantly longer median progression-free 
    Output:
    
Conclusions : In patients with advanced NSCLC harbouring exon 19 deletions , TKIs are associated with better OS compared with conventional chemotherapy .