***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: 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 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 Non-r and omised studies of the effects of interventions are critical to many areas of healthcare evaluation , but their results may be biased . It is therefore important to underst and and appraise their strengths and weaknesses . We developed ROBINS-I ( “ Risk Of Bias In Non-r and omised Studies - of Interventions ” ) , a new tool for evaluating risk of bias in estimates of the comparative effectiveness ( harm or benefit ) of interventions from studies that did not use r and omisation  to allocate units ( individuals or clusters of individuals ) to comparison groups . The tool will be particularly useful to those undertaking systematic review s that include non-r and omised studies Purpose : To evaluate the efficacy and safety of gefitinib plus simvastatin ( GS ) versus gefitinib alone ( G ) in previously treated patients with advanced non – small cell lung cancer ( NSCLC ) . Experimental Design : Between May 2006 and September 2008 , 106 patients ( 51 % men , 75 % adenocarcinoma , 50 % never smoker ) were r and omly assigned to G alone ( 250 mg/d , n = 54 ) or GS ( 250 and 40 mg/d , respectively , n = 52 ) . One cycle was 4 weeks of treatment . Therapy was continued until disease progression or intolerable toxicity was observed . The primary endpoint was response rate ( RR ) . Secondary endpoints included toxicity , progression-free survival ( PFS ) , and overall survival ( OS ) . Results : The RR was 38.5 % ( 95 % CI , 25.3–51.7 ) for GS and 31.5 % ( 95 % CI , 19.1–43.9 ) for G. The median PFS was 3.3 months [ M ] ( 95 % CI , 1.4–5.2 M ) for GS and 1.9 M ( 95 % CI , 1.0–2.8 M ) for G. The median OS was 13.6 M ( 95 % CI , 7.1–20.1 M ) for GS and 12.0 M ( 95 % CI , 7.8–16.2 M ) for G. In exploratory subgroup analysis , GS showed higher RR ( 40 % vs. 0 % , P = 0.043 ) and longer PFS ( 3.6 M vs. 1.7 M , P = 0.027 ) compared with G alone in patients with wild-type epidermal growth factor receptor ( EGFR ) nonadenocarcinomas .  Adverse events in both arms were generally mild and mainly consisted of skin rashes . Conclusions : Although no superiority of GS to G was demonstrated in this unselected NSCLC population , GS showed higher RR and longer PFS compared with G alone in patients with wild-type EGFR nonadenocarcinomas .  Simvastatin may improve the efficacy of gefitinib in that subgroup of gefitinib-resistant NSCLC patients . Clin Cancer Res ; 17(6 ) ; 1553–60 . © 2011 AACR BACKGROUND Erlotinib has been shown to improve progression-free survival compared with chemotherapy when given as first-line treatment for Asian patients with non-small-cell lung cancer ( NSCLC ) with activating EGFR mutations . We aim ed to assess the safety and efficacy of erlotinib compared with st and ard chemotherapy for first-line treatment of European patients with advanced EGFR-mutation positive NSCLC . METHODS We undertook the open-label , r and omised phase 3 EURTAC trial at 42 hospitals in France , Italy , and Spain . Eligible participants were adults ( > 18 years ) with NSCLC and EGFR mutations ( exon 19 deletion or L858R mutation in exon 21 ) with no history of chemotherapy for metastatic disease ( neoadjuvant or adjuvant chemotherapy ending ≥ 6 months before study entry was allowed ) . We r and omly allocated participants ( 1:1 ) according to a computer-generated allocation schedule to receive oral erlotinib 150 mg per day or 3 week cycles of st and ard intravenous chemotherapy of cisplatin 75 mg/m(2 ) on day 1 plus docetaxel ( 75 mg/m(2 ) on day 1 ) or gemcitabine ( 1250 mg/m(2 ) on days 1 and 8) . Carboplatin ( AUC 6 with docetaxel 75 mg/m(2 ) or AUC 5 with gemcitabine 1000 mg/m(2 ) ) was allowed in patients unable to have cisplatin . Patients were stratified by EGFR mutation type and Eastern Cooperative Oncology Group performance status ( 0 vs 1 vs 2 ) . The primary endpoint was progression-free survival ( PFS ) in the intention-to-treat population . We assessed safety in all patients who received study drug ( ≥ 1 dose ) . This study is registered with Clinical Trials.gov , number NCT00446225 . FINDINGS Between Feb 15 , 2007 , and Jan 4 , 2011 , 174 patients with EGFR mutations were enrolled . One patient received treatment before r and omisation and was thus withdrawn from the study ; of the remaining patients , 86 were r and omly assigned to receive erlotinib and 87 to receive st and ard chemotherapy . The preplanned interim analysis showed that the study met its primary endpoint ; enrolment was halted , and full evaluation of the results was recommended . At data cutoff ( Jan 26 , 2011 ) , median PFS was 9·7 months ( 95 % CI 8·4 - 12·3 ) in the erlotinib group , compared with 5·2 months ( 4·5 - 5·8 ) in the st and ard chemotherapy group ( hazard ratio 0·37 , 95 % CI 0·25 - 0·54 ; p < 0·0001 ) . Main grade 3 or 4 toxicities were rash ( 11 [ 13 % ] of 84 patients given erlotinib vs none of 82 patients in the chemotherapy group ) , neutropenia ( none vs 18 [ 22 % ] ) , anaemia ( one [ 1 % ] vs three [ 4 % ] ) , and increased amino-transferase concentrations ( two [ 2 % ] vs 0 ) . Five ( 6 % ) patients on erlotinib  had treatment-related severe adverse events compared with 16 patients ( 20 % ) on chemotherapy . One patient in the erlotinib group and two in the st and ard chemotherapy group died from treatment-related causes . INTERPRETATION Our findings strengthen the rationale for routine baseline tissue-based assessment of EGFR mutations in patients with NSCLC and for treatment of mutation-positive patients with EGFR tyrosine-kinase inhibitors . FUNDING Spanish Lung Cancer Group , Roche Farma , Hoffmann-La Roche , and Red Temática de Investigacion Cooperativa en Cancer OBJECTIVES Prior studies have shown an anticancer effect of statins in patients with certain malignancies . However , it is unclear whether statins have a mortality benefit in lung cancer . We compared survival of patients with stage IV non-small cell lung cancer ( NSCLC ) receiving vs. not receiving statins prior to diagnosis . METHODS Using data from the Surveillance , Epidemiology and End Results registry linked to Medicare cl aims , we identified 5118 patients > 65 years of age diagnosed with stage IV NSCLC between 2007 and 2009 . We used propensity score methods to assess the association of statin use with overall and lung cancer-specific survival while controlling for measured confounders . RESULTS Overall , 27 % of patients were on statins  at time of lung cancer diagnosis . Median survival in the statin group was 7 months , compared to 4 months in patients not treated with statins ( p<0.001 ) . Propensity score analyses found that statin use was associated with improvement in overall ( hazard ratio [ HR ] : 0.76 , 95 % confidence interval [ CI ] : 0.73 - 0.79 ) and lung cancer-specific survival ( HR : 0.77 , 95 % CI : 0.73 - 0.81 ) , after controlling for baseline patient characteristics , cancer characteristics , staging work-up and chemotherapy use . CONCLUSIONS Statin use is associated with improved survival among patients with stage IV NSCLC suggesting a potential anticancer effect . Further research should evaluate plausible biological mechanisms as well as test the effect of statins in prospect i ve clinical trials 
    Output:
    
This systematic review and meta- analysis aims to describe the prognostic effects of  statins  in patients with NSCLC , which would help clinicians to optimise treatment for patients with NSCLC .