***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 : The safety , pharmacokinetics , and clinical activity of pazopanib ( GW786034 ) , an oral angiogenesis inhibitor targeting vascular endothelial growth factor receptor , platelet-derived growth factor receptor , and c-Kit , were evaluated in patients with advanced-stage refractory solid tumors . Experimental Design : Patients were enrolled into sequential dose-escalating cohorts ( 50 mg three times weekly to 2,000 mg once daily and 300 - 400 mg twice daily ) . Escalation or deescalation was based on toxicities observed in the preceding dose cohort . Pharmacokinetic and biomarker sample s were obtained . Clinical response was assessed every 9 weeks . Results : Sixty-three patients were treated ( dose escalation , n = 43 ; dose expansion , n = 20 ) . Hypertension , diarrhea , hair depigmentation , and nausea were the most frequent drug-related adverse events , the majority of which were of grade 1/2 . Hypertension was the most frequent grade 3 adverse event . Four patients experienced dose-limiting toxicities at 50 mg , 800 mg , and 2,000 mg once daily . A plateau in steady-state exposure was observed at doses of ≥800 mg once daily . The mean elimination half-life at this dose was 31.1 hours . A mean target trough concentration ( C24 ) ≥15 μg/mL ( 34 μmol/L ) was achieved at 800 mg once daily . Three patients had partial responses ( two confirmed , one unconfirmed ) , and stable disease of ≥6 months was observed in 14 patients ; clinical benefit was generally observed in patients who received doses of ≥800 mg once daily or 300 mg twice daily . Conclusion : Pazopanib was generally well tolerated and showed antitumor activity across various tumor types . A monotherapy dose of 800 mg once daily was selected for phase II studies Purpose BIRCH was design ed to examine the efficacy of atezolizumab , a humanized anti-programmed death-lig and 1 ( PD-L1 ) monoclonal antibody , in advanced non-small-cell lung cancer ( NSCLC ) across lines of therapy . Patients were selected on the basis of PD-L1 expression on tumor cells ( TC ) or tumor-infiltrating immune cells ( IC ) . Patients and Methods Eligible patients had advanced-stage NSCLC , no CNS metastases , and zero to two or more lines of prior chemotherapy . Patients whose tumors expressed PD-L1 using the SP142 immunohistochemistry assay on ≥ 5 % of TC or IC ( TC2/3 or IC2/3 [ TC or IC ≥ 5 % PD-L1-expressing cells , respectively ] ) were enrolled . Atezolizumab 1,200 mg was administered intravenously every 3 weeks . Efficacy-evaluable patients ( N = 659 ) comprised three cohorts : first line ( cohort 1 ; n = 139 ) ; second line ( cohort 2 ; n = 268 ) ; and third line or higher ( cohort 3 ; n = 252 ) . The primary end point was independent review facility-assessed objective response rate ( ORR ; Response Evaluation Criteria in Solid Tumors [ RECIST ] version 1.1 ) . Secondary end points included median duration of response , progression-free survival , and overall survival ( OS ) . Results BIRCH met its primary objective of demonstrating a significant ORR versus historical controls . With a minimum of 12 months of follow-up , the independent review facility-assessed ORR was 18 % to 22 % for the three cohorts , and 26 % to 31 % for the TC3 or IC3 subgroup ; most responses are ongoing . Responses occurred regardless of EGFR or KRAS mutation status . The median OS from an up date d survival analysis ( minimum of 20 month follow up ) for cohort 1 was 23.5 months ( 26.9 months for TC3 or IC3 patients ) ; the median OS in cohorts 2 and 3 was 15.5 and 13.2 months , respectively . The safety profile was similar across cohorts and consistent with previous atezolizumab monotherapy trials . Conclusion BIRCH demonstrated responses with atezolizumab monotherapy in patients with PD-L1-selected advanced NSCLC , with good tolerability . PD-L1 status may serve as a predictive biomarker for identifying patients most likely to benefit from atezolizumab PURPOSE Effective systemic therapy for advanced carcinoid is lacking . The combination of bevacizumab ( BEV ) and pegylated ( PEG ) interferon alpha-2b was evaluated among patients with metastatic or unresectable carcinoid tumors . PATIENTS AND METHODS Forty-four patients on stable doses of octreotide  were r and omly assigned to 18 weeks of treatment with bevacizumab or PEG interferon alpha-2b . At disease progression ( PD ) or at the end of 18 weeks ( whichever occurred earlier ) , patients received bevacizumab plus PEG interferon until progression . Functional computer tomography ( CT ) scans were performed to measure effect on tumor blood flow . RESULTS In the bevacizumab arm , four patients ( 18 % ) achieved confirmed partial response ( PR ) , 17 patients ( 77 % ) had stable disease ( SD ) , and one patient ( 5 % ) had PD . In the PEG interferon arm , 15 patients ( 68 % ) had SD and six patients ( 27 % ) had PD . Progression-free survival ( PFS ) rates after 18 weeks of monotherapy were 95 % in bevacizumab versus 68 % on the PEG interferon arm . The overall median PFS for all 44 patients is 63 weeks . Compared with paired baseline measurements on functional CT scans , we observed a 49 % ( P < .01 ) and 28 % ( P < .01 ) decrease in tumor blood flow at day 2 and week 18 among patients treated with bevacizumab . No significant changes in tumor blood flow were observed following PEG interferon . PEG interferon alpha-2b treatment was associated with decrease in plasma basic fibroblast growth factor ( bFGF ; P = .04 ) and increase in plasma interleukin-18 ( IL-18 ; P < .01 ) . No significant changes in bFGF or IL-18 following treatment with bevacizumab were observed . CONCLUSION Bevacizumab therapy result ed in objective responses , reduction of tumor blood flow , and longer PFS in patients with carcinoid than PEG interferon treatment BACKGROUND Outcomes are poor for patients with previously treated , advanced or metastatic non-small-cell lung cancer ( NSCLC ) . The anti-programmed death lig and 1 ( PD-L1 ) antibody atezolizumab is clinical ly active against cancer , including NSCLC , especially cancers expressing PD-L1 on tumour cells , tumour-infiltrating immune cells , or both . We assessed efficacy and safety of atezolizumab versus docetaxel in previously treated NSCLC , analysed by PD-L1 expression levels on tumour cells and tumour-infiltrating immune cells and in the intention-to-treat population . METHODS In this open-label , phase 2 r and omised controlled trial , patients with NSCLC who progressed on post-platinum chemotherapy were recruited in 61 academic medical centres and community oncology practice s across 13 countries in Europe and North America . Key inclusion criteria were Eastern Cooperative Oncology Group performance status 0 or 1 , measurable disease by Response Evaluation Criteria In Solid Tumors version 1.1 ( RECIST v1.1 ) , and adequate haematological and end-organ function . Patients were stratified by PD-L1 tumour-infiltrating immune cell status , histology , and previous lines of therapy , and r and omly assigned ( 1:1 ) by permuted block r and omisation ( with a block size of four ) using an interactive voice or web system to receive intravenous atezolizumab 1200 mg or docetaxel 75 mg/m(2 ) once every 3 weeks . Baseline PD-L1 expression was scored by immunohistochemistry in tumour cells ( as percentage of PD-L1-expressing tumour cells TC3≥50 % , TC2≥5 % and < 50 % , TC1≥1 % and < 5 % , and TC0<1 % ) and tumour-infiltrating immune cells ( as percentage of tumour area : IC3≥10 % , IC2≥5 % and < 10 % , IC1≥1 % and < 5 % , and IC0<1 % ) . The primary endpoint was overall survival in the intention-to-treat population and PD-L1 subgroups at 173 deaths . Biomarkers were assessed in an exploratory analysis . We assessed safety in all patients who received at least one dose of study drug . This study is registered with Clinical Trials.gov , number NCT01903993 . FINDINGS Patients were enrolled between Aug 5 , 2013 , and March 31 , 2014 . 144 patients were r and omly allocated to the  atezolizumab group , and 143 to the docetaxel group . 142 patients received at least one dose of atezolizumab and 135 received docetaxel  . Overall survival in the intention-to-treat population was 12·6 months ( 95 % CI 9·7 - 16·4 ) for atezolizumab versus 9·7 months ( 8·6 - 12·0 ) for docetaxel ( hazard ratio [ HR ] 0·73 [ 95 % CI 0·53 - 0·99 ] ; p=0·04 ) . Increasing improvement in overall survival was associated with increasing PD-L1 expression ( TC3 or IC3 HR 0·49 [ 0·22 - 1·07 ; p=0·068 ] , TC2/3 or IC2/3 HR 0·54 [ 0·33 - 0·89 ; p=0·014 ] , TC1/2/3 or IC1/2/3 HR 0·59 [ 0·40 - 0·85 ; p=0·005 ] , TC0 and IC0 HR 1·04 [ 0·62 - 1·75 ; p=0·871 ] ) . In our exploratory analysis , patients with pre-existing immunity , defined by high T-effector-interferon-γ-associated gene expression , had improved overall survival  with atezolizumab . 11 ( 8 % ) patients in the atezolizumab group discontinued because of adverse events versus 30 ( 22 % ) patients in the docetaxel group . 16 ( 11 % ) patients in the atezolizumab group versus 52 ( 39 % ) patients in the docetaxel group had treatment-related grade 3 - 4 adverse events , and one ( < 1 % ) patient in the atezolizumab group versus three ( 2 % ) patients in the docetaxel group died from a treatment-related adverse event . INTERPRETATION Atezolizumab significantly improved survival compared with docetaxel in patients with previously treated NSCLC . Improvement correlated with PD-L1 immunohistochemistry expression on tumour cells and tumour-infiltrating immune cells , suggesting that PD-L1 expression is predictive for atezolizumab benefit . Atezolizumab was well tolerated , with a safety profile distinct from chemotherapy . FUNDING F Hoffmann-La Roche/Genentech PURPOSE To establish the safety , pharmacokinetics , and recommended dose of sunitinib , a novel oral multitargeting tyrosine kinase inhibitor with antiangiogenic and antitumor properties , in patients with advanced malignancies . PATIENTS AND METHODS Sunitinib was given orally for 4 weeks every 6 weeks . RESULTS Twenty-eight patients received doses ranging from 15 to 59 mg/m2 ( ranging from 50 mg every other day to 150 mg/d ) .  Dose-limiting toxicities reported at the maximum-tolerated doses > or = 75 mg/d were reversible grade 3 fatigue , grade 3 hypertension , and grade 2 bullous skin toxicity . Therefore , the recommended dose was 50 mg/d . At this dose , the main adverse effects were sore mouth , edema , and thrombocytopenia . Hair discoloration and yellow coloration of the skin were observed at doses > or = 50 mg/d . Pharmacokinetic data indicate that potentially active target plasma concentrations > or = 50 ng/mL can be achieved with moderate interpatient variability and a long half-life compatible with a single daily dosing . Six objective responses were observed in three renal cell carcinomas , one neuroendocrine tumor , one stromal tumor , and one unknown primary adenocarcinoma patient . At higher doses ( > or = 75 mg/d ) , tumor responses were often associated with reduced intratumoral vascularization and central tumor necrosis , eventually result ing in organ perforation or fistula . CONCLUSION At the dose of 50 mg/d ( 4 weeks on , 2 weeks off 
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Conclusions : Pazopanib monotherapy achieved a DCR of 90.3 % in patients with locally advanced and /or metastatic neuroendocrine neoplasia , with an overall response rate comparable to other TKIs and mTOR inhibitors and a safety profile similar to that of drugs of the same class