***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: PURPOSE Bevacizumab is a monoclonal antibody that targets vascular endothelial growth factor ( VEGF ) with demonstrated efficacy in combination with carboplatin and paclitaxel ( PCB ) for the treatment of advanced non-small-cell lung cancer ( NSCLC ) . Administration of bevacizumab is postulated to decrease nitric oxide synthesis and lead to hypertension , which may be a physiological sign that the VEGF pathway is more actively being blocked and could result in improved outcomes . PATIENTS AND METHODS Eastern Cooperative Oncology Group ( ECOG ) 4599 r and omly assigned patients with nonsquamous NSCLC to carboplatin and paclitaxel ( PC ) versus PCB .  Hypertensive patients were compared with nonhypertensive patients with respect to overall survival ( OS ) and progression-free survival ( PFS ) using blood pressure data and adverse event data separately . High blood pressure ( HBP ) by the end of cycle 1 was defined as blood pressure > 150/100 at any previous time or at least a 20-mmHg increase in diastolic blood pressure from baseline . Results In a multivariable Cox model adjusting for HBP as a time-varying covariate , comparing those on PCB with HBP with those on PC gave an OS hazard ratio ( HR ) of 0.60 ( 95 % CI , 0.43 to 0.81 ; P = .001 ) ; comparing those on PCB without HBP with those on PC alone , the OS HR was 0.86 ( 95 % CI , 0.74 to 1.00 ; P = .05 ) . Comparing the PCB HBP group with PC gave an adjusted PFS HR of 0.54 ( 95 % CI , 0.41 to 0.73 ; P < .0001 ) and comparing those on PCB without HBP to those on PC , the HR was 0.72 ( 95 % CI , 0.62 to 0.84 ; P < .0001 ) . The 6-month cumulative incidence of hypertension was 6.2 % ( 95 % CI , 3.9 % to 8.6 % ) . CONCLUSION Data from ECOG 4599 suggest that onset of HBP during treatment with PCB may be associated with improved outcomes , and additional studies of the downstream effects of VEGF suppression and hypertension are needed PURPOSE Bevacizumab , a humanized anti-vascular endothelial growth factor monoclonal antibody , and erlotinib , a reversible , orally available epidermal growth factor receptor tyrosine kinase inhibitor , have demonstrated evidence of a survival benefit in the treatment of non-small-cell lung cancer ( NSCLC ) . A single-arm phase I and II study of bevacizumab plus erlotinib demonstrated encouraging efficacy , with a favorable safety profile . PATIENTS AND METHODS A multicenter , r and omized phase II trial evaluated the safety of combining bevacizumab with either chemotherapy ( docetaxel or pemetrexed ) or erlotinib and preliminarily assessed these combinations versus chemotherapy alone , as measured by progression-free survival ( PFS ) .  All patients had histologically confirmed nonsquamous NSCLC that had progressed during or after one platinum-based regimen . RESULTS One hundred twenty patients were r and omly assigned and treated . No unexpected adverse events were noted . Fewer patients ( 13 % ) in the bevacizumab-erlotinib arm discontinued treatment as a result of adverse events than in the chemotherapy alone ( 24 % ) or bevacizumab-chemotherapy ( 28 % ) arms . The incidence of grade 5 hemorrhage in patients receiving bevacizumab was 5.1 % . Although not statistically significant , relative to chemotherapy alone , the risk of disease progression or death was 0.66 ( 95 % CI , 0.38 to 1.16 ) among patients treated with bevacizumab-chemotherapy and 0.72 ( 95 % CI , 0.42 to 1.23 ) among patients treated with bevacizumab-erlotinib .  One-year survival rate was 57.4 % for bevacizumab-erlotinib and 53.8 % for bevacizumab-chemotherapy compared with 33.1 % for chemotherapy alone . CONCLUSION Results for PFS and overall survival favor combination of bevacizumab with either chemotherapy or erlotinib over chemotherapy alone in the second-line setting . No unexpected safety signals were noted . The rate of fatal pulmonary hemorrhage was consistent with previous bevacizumab trials . The toxicity profile of the bevacizumab-erlotinib combination is favorable compared with either chemotherapy-containing group Background : Bevacizumab , the anti-vascular endothelial growth factor agent , provides clinical benefit when combined with platinum-based chemotherapy in first-line advanced non-small-cell lung cancer . We report the final overall survival ( OS ) analysis from the phase III AVAiL trial . Patients and methods : Patients ( n = 1043 ) received cisplatin 80 mg/m2 and gemcitabine 1250 mg/m2 for up to six cycles plus bevacizumab 7.5 mg/kg ( n = 345 ) , bevacizumab 15 mg/kg ( n = 351 ) or placebo ( n = 347 ) every 3 weeks until progression . Primary end point was progression-free survival ( PFS ) ; OS was a secondary end point . Results : Significant PFS prolongation  with bevacizumab compared with placebo was maintained with longer follow-up { hazard ratio ( HR ) [ 95 % confidence interval ( CI ) ] 0.75 ( 0.64–0.87 ) , P = 0.0003 and 0.85 ( 0.73–1.00 ) , P = 0.0456 } for the 7.5 and 15 mg/kg groups , respectively . Median OS was > 13 months in all treatment groups ; nevertheless , OS was not significantly increased with bevacizumab [ HR ( 95 % CI ) 0.93 ( 0.78–1.11 ) , P = 0.420 and 1.03 ( 0.86–1.23 ) , P = 0.761 ] for the 7.5 and 15 mg/kg groups , respectively , versus placebo . Most patients ( ∼62 % ) received multiple lines of post study treatment . Up date d safety results are consistent with those previously reported . Conclusions : Final analysis of AVAiL confirms the  efficacy of bevacizumab when combined with cisplatin – gemcitabine . The PFS benefit did not translate into a significant OS benefit , possibly due to high use of efficacious second-line therapies BACKGROUND We conducted a r and omized study to determine whether any of three chemotherapy regimens was superior to cisplatin and paclitaxel in patients with advanced non-small-cell lung cancer . METHODS A total of 1207 patients with advanced non-small-cell lung cancer were r and omly assigned to a reference regimen of cisplatin and paclitaxel or to one of three experimental regimens : cisplatin and gemcitabine , cisplatin and docetaxel , or carboplatin and paclitaxel . RESULTS The response rate for all 1155 eligible patients was 19 percent , with a median survival of 7.9 months ( 95 percent confidence interval , 7.3 to 8.5 ) , a 1-year survival rate of 33 percent ( 95 percent confidence interval , 30 to 36 percent ) , and a 2-year survival rate of 11 percent ( 95 percent confidence interval , 8 to 12 percent ) . The response rate and survival did not differ significantly between patients assigned to receive cisplatin and paclitaxel and those assigned to receive any of the three experimental regimens . Treatment with cisplatin and gemcitabine was associated with a significantly longer time to the progression of disease than was treatment with cisplatin and paclitaxel but was more likely to cause grade 3 , 4 , or 5 renal toxicity ( in 9 percent of patients , vs. 3 percent of those treated with cisplatin plus paclitaxel ) . Patients with a performance status of 2 had a significantly lower rate of survival than did those with a performance status of 0 or 1 . CONCLUSIONS None of four chemotherapy regimens offered a significant advantage over the others in the treatment of advanced non-small-cell lung cancer BACKGROUND Results of two phase 3 trials have shown first-line bevacizumab in combination with chemotherapy improves clinical outcomes in patients with advanced or recurrent non-squamous non-small-cell lung cancer ( NSCLC ) . The SAiL ( MO19390 ) study was undertaken to assess the safety and efficacy of first-line bevacizumab combined with st and ard chemotherapy regimens in clinical practice . METHODS Between August , 2006 , and June , 2008 , patients with untreated locally advanced , metastatic , or recurrent non-squamous NSCLC were recruited to this open-label , single group , phase 4 study from centres in 40 countries . Eligible patients had histologically or cytologically documented inoperable , locally advanced , metastatic , or recurrent disease ( stage IIIB-IV ) ; an Eastern Cooperative Oncology Group performance status of 0 - 2 ; and adequate haematological , hepatic , and renal function . Patients received bevacizumab ( 7.5 or 15 mg/kg every 3 weeks ) plus st and ard chemotherapy for up to six cycles , followed by single-agent bevacizumab until disease progression . The primary endpoint was safety ; analysis was by intention to treat ( ITT ) . This study is registered with Clinical Trials.gov , number NCT00451906 . FINDINGS At the final data cutoff ( July 24 , 2009 ) , an ITT population of 2212 patients was assessed . The incidence of clinical ly significant ( grade > or = 3 ) adverse events of special interest was generally low ; thromboembolism occurred in 172 ( 8 % ) patients , hypertension in 125 ( 6 % ) , bleeding in 80 ( 4 % ) , proteinuria in 67 ( 3 % ) , and pulmonary haemorrhage in 15 ( 1 % ) . 57 ( 3 % ) patients died because of these adverse events , with thromboembolism ( 26 patients , 1 % ) and bleeding ( 17 , 1 % ) as the most common causes . The most common grade 3 or higher serious adverse events deemed by investigators to be associated with bevacizumab were pulmonary embolism ( 28 patients ; 1 % ) and epistaxis , neutropenia , febrile neutropenia , and deep vein thrombosis ( all of which occurred in 13 patients [ 1 % ] ) . Bevacizumab was temporarily interrupted after 28 ( 2 % ) of 1347 bleeding events and 72 ( 7 % ) of 1025 hypertension events , and permanently discontinued after 110 ( 8 % ) bleeding events and 40 ( 4 % ) hypertension events . No new safety signals were reported . INTERPRETATION Our results confirm the manageable safety profile of first-line bevacizumab in combination with various st and ard chemotherapy regimens for treatment of  advanced  non-squamous NSCLC . FUNDING F Hoffmann-La Roche 8036^ Background : Two phase III trials ( ECOG 4599 and BO17704 ) demonstrated that the addition of bevacizumab ( Bev ) to platinum-based regimens improved overall and /or progression-free survival ( PFS ) in patients ( pts ) with advanced non-squamous NSCLC ( S and ler et al. NEJM 2006 ; Manegold et al. ESMO2008 ) . However , no investigation with Bev has been conducted in Japanese NSCLC pts . METHODS This r and omized , open-label phase II study compared a 3-weekly regimen of 15mg/kg of Bev plus carboplatin/paclitaxel ( CP ) versus CP alone . The primary endpoint was PFS ; secondary endpoints included overall survival ( OS ) , response rate ( RR ) and safety .  Eligibility criteria : histologically or cytologically documented previously untreated advanced or recurrent non-squamous NSCLC ; ECOG PS 0 - 1 ; no brain metastases . A size of 180 pts was planned to be r and omized to : C AUC=6 and P 200mg/m2 q3 wks for up to 6 cycles plus Bev continued to progression at 15mg/kg q3 wks , or CP alone at the r and omization ratio of 2:1 . The study was design ed to observe a 20 % reduction in the risk of a PFS event in the Bev arm compared with control . RESULTS Between 4/07 and 3/08 , 180 pts were accrued . Three pts of them were ineligible and 3 pts were not dosed at all . PFS ( as assessed by investigators ) and RR were significantly improved . OS is immature due to short duration of follow up . Up date d PFS results as assessed by the central review committee and OS data will be provided . No new safety signals for Bev were detected . CONCLUSIONS This is the first study of Bev in Japanese pts with NSCLC . The addition of 15mg 
    Output:
    
Conclusions The addition of bevacizumab to chemotherapy in patients with advanced NSCLC  prolongs OS , PFS and RR .
Considering the toxicities added , and the small absolute benefits found , bevacizumab plus platinum-based chemotherapy can be considered an option in selected patients with advanced NSCLC .