***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: A phase III r and omized trial was conducted to investigate whether induction chemotherapy followed by radiation can influence survival as compared with radiation alone in unresectable , locally advanced non-small-cell lung cancer ( LADNSCLC ) . A total of 101 patients with unresectable stage IIIA or IIIB NSCLC were enrolled . Patients were stratified by performance status , weight loss , histology and stage , and then r and omized to receive combined chemoradiotherapy or radiotherapy alone . Radiotherapy was administered in 1.8 Gy to 2.0 Gy st and ard fractions daily 5 times weekly for a total dose of 60 Gy to 65 Gy . The combined group received induction of cisplatin , etoposide , and vinblastine ( PEV ) chemotherapy with cisplatin 20 mg/m2 on days 1 to 5 , etoposide 100 mg/m2 on days 2 to 4 , and vinblastine 6 mg/m2 on day 1 , which wasrepeated every 3 weeks for 3 courses , after which time the patients underwent radiotherapy .  Of 101 patients registered , 89 patients ( 43 combined , 46 radiotherapy alone ) were eligible for analysis . The response rates for the combined and radiotherapy groups were 65 % ( 28/43 ) and 70 % ( 32/46 ) , respectively . The median survival time ( MST ) showed a tendency to be more prolonged in the combined group than in the group receiving radiotherapy alone ( 13.8 vs. 8.5 months ) . The MST in patients with nonsquamous histology was strikingly prolonged in the combined group as compared with the radiotherapy group ( 14 vs. 3.6 months , p 0.027 ) . Likewise , the MST in patients with stage IIIB was significantly prolonged in the combined group as compared with the radiotherapy group ( 11.1 vs. 7.2 months , p 0.045 ) . Together , the MST of the high-risk group with nonsquamous or stage IIIB was significantly higher in the combined group than that seen in the radiotherapy group ( 11.6 vs. 8 months , p 0.046 ) , whereas the MST of the low-risk group , defined as having both squamous histology and stage IIIA , was similar in the two treatment groups ( 18.3 vs. 20.8 months , p = 0.293 ) . In conclusion , induction PEV chemotherapy plus radiotherapy is superior to radiotherapy alone in high-risk subsets of unresectable LAD-NSCLC and therapeutic strategy should be based on the identification of prognostic factors Background Gefitinib is an oral EGFR tyrosine kinase inhibitors which may act as a radiosensitizer . Patients and Methods This phase II study evaluated the efficacy of gefitinib 250 mg once daily in combination with thoracic radiotherapy ( 66 Gy in 6.5 weeks , 2 Gy/day , 5 fractions/week ) followed by consolidation chemotherapy ( IV cisplatin and vinorelbine ) as first line treatment in a population of unselected stage IIIB NSCLC patients according to EGFR mutation status . Results Due to a low accrual rate in this study , the sample size ( n = 50 ) was not reached . Sixteen patients were included in four centers , 50 % had adenocarcinoma and 75 % were male .  Genomic alterations ( 7 patients studied ) retrieved TP53 mutation in 2 patients and no EGFR mutation . Four weeks after radiotherapy , 3 patients ( 19 % ) had a partial response , 6 ( 38 % ) had a stable disease , and 7 had a progression ( 44 % ) . Median overall survival was 11 months and median progression-free survival was 5 months . At the time of the last contact , 5 patients ( 31 % ) were still alive . Main toxicities were gastrointestinal ( 81 % ) , cutaneous ( 81 % ) , general ( 56 % ) , and respiratory ( 50 % ) . There were 12>G3 adverse events in 7 ( 47 % ) patients , and there was one toxic-death during the concomitant period due to an interstitial pneumonitis . There were two possible adverse events-related deaths during the chemotherapy period ( pulmonary embolism ( n = 1 ) and sudden death after the administration of the 3rd course of chemotherapy ( n = 1 ) ) . Conclusion The benefit of Gefitinib-RT could not be confirmed due to premature trial discontinuation . Further evaluation is required , especially in patients with EGFR mutated NSCLC BACKGROUND The efficacy of the ALK inhibitor crizotinib as compared with st and ard chemotherapy as first-line treatment for advanced ALK-positive non-small-cell lung cancer ( NSCLC ) is unknown . METHODS We conducted an open-label , phase 3 trial comparing crizotinib with chemotherapy in 343 patients with advanced ALK-positive nonsquamous NSCLC who had received no previous systemic treatment for advanced disease . Patients were r and omly assigned to receive oral crizotinib at a dose of 250 mg twice daily or to receive intravenous chemotherapy ( pemetrexed , 500 mg per square meter of body-surface area , plus either cisplatin , 75 mg per square meter , or carboplatin , target area under the curve of 5 to 6 mg per milliliter per minute ) every 3 weeks for up to six cycles . Crossover to crizotinib treatment after disease progression was permitted for patients receiving chemotherapy . The primary end point was progression-free survival as assessed by independent radiologic review . RESULTS Progression-free survival was significantly longer with crizotinib than with chemotherapy ( median , 10.9 months vs. 7.0 months ; hazard ratio for progression or death with crizotinib , 0.45 ; 95 % confidence interval [ CI ] , 0.35 to 0.60 ; P<0.001 ) . Objective response rates were 74 % and 45 % , respectively ( P<0.001 ) . Median overall survival was not reached in either group ( hazard ratio for death with crizotinib , 0.82 ; 95 % CI , 0.54 to 1.26 ; P=0.36 ) ; the probability of 1-year survival was 84 % with crizotinib and 79 % with chemotherapy . The most common adverse events with crizotinib were vision disorders , diarrhea , nausea , and edema , and the most common events with chemotherapy were nausea , fatigue , vomiting , and decreased appetite . As compared with chemotherapy , crizotinib was associated with greater reduction in lung cancer symptoms and greater improvement in quality of life . CONCLUSIONS Crizotinib was superior to st and ard first-line pemetrexed-plus-platinum chemotherapy in patients with previously untreated advanced ALK-positive NSCLC . ( Funded by Pfizer ; PROFILE 1014 Clinical Trials.gov number , NCT01154140 . ) 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 Concurrent chemoradiotherapy ( CCRT ) is the st and ard care for stage III non-small cell lung cancer ( NSCLC ) patients ; however , a more effective regimen is needed to improve the outcome by better controlling occult metastases . We conducted two parallel r and omized phase II studies to incorporate erlotinib or irinotecan-cisplatin ( IP ) into CCRT for stage III NSCLC depending on epidermal growth factor receptor ( EGFR ) mutation status . Material s and Methods Patients with EGFR-mutant tumors were r and omized to receive three cycles of erlotinib first and then either CCRT with erlotinib followed by erlotinib ( arm A ) or CCRT with IP only ( arm B ) . Patients with EGFR unknown or wild-type tumors were r and omized to receive either three cycles of IP before ( arm C ) or after CCRT with IP ( arm D ) . Results Seventy-three patients were screened and the study was closed early because of slow accrual after 59 patients were r and omized . Overall , there were seven patients in arm A , five in arm B , 22 in arm C , and 25 in arm D. The response rate was 71.4 % and 80.0 % for arm A and B , and 70.0 % and 73.9 % for arm C and D. The median overall survival ( OS ) was 39.3 months versus 31.2 months for arm A and B ( p=0.442 ) , and 16.3 months versus 25.3 months for arm C and D ( p=0.050 ) . Patients with sensitive EGFR mutations had significantly longer OS than EGFR-wild patients ( 74.8 months vs. 25.3 months , p=0.034 ) . There were no unexpected toxicities . Conclusion Combined-modality treatment by molecular diagnostics is feasible in stage III NSCLC . EGFR-mutant patients appear to be a distinct subset with longer survival Background Concurrent chemoradiotherapy is the st and ard of care for inoperable stage III non-small cell lung cancer ( NSCLC ) for patients who can tolerate it . We explored if adding erlotinib would increase the effectiveness of chemoradiotherapy  without increasing toxicity in a single-arm prospect i ve phase II trial . Methods Forty-eight patients with previously untreated NSCLC received intensity-modulated radiation therapy ( 63 Gy/35 fractions ) on Monday – Friday , with chemotherapy ( paclitaxel 45 mg/m2 , carboplatin AUC=2 ) on Mondays , for 7 weeks . All patients also received the epidermal growth factor receptor ( EGFR ) tyrosine kinase inhibitor erlotinib ( 150 mg orally 1/day ) on Tuesday – Sunday for 7 weeks followed by consolidation paclitaxel – carboplatin . The primary endpoint was time to progression ; secondary endpoints were overall survival ( OS ) , toxicity , response , and disease control and whether any endpoint differed by EGFR mutation status . Results Of 46 patients evaluable for response , 40 were former or never-smokers and 41 were evaluable for EGFR mutations ( 37 wild-type [ wt ] and 4 [ mutated ; all 
    Output:
    
There is evidence , albeit of low quality , that added the TKIs to TRT or CRT may improve RR and survival outcomes  in patients with EGFR mutant status unknown advanced or metastatic NSCLC relative to other studies of TKIs alone , TRT alone or CRT