***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 This trial evaluated the efficacy of maintenance erlotinib , an epidermal growth factor receptor ( EGFR ) tyrosine kinase inhibitor , after first-line chemotherapy . PATIENTS AND METHODS Eligible patients had high-risk International Federation of Gynecology and Obstetrics stage I or stage II to IV epithelial ovarian , primary peritoneal , or fallopian tube cancer and were not selected for EGFR expression . All patients underwent first-line platinum-based chemotherapy ( CT ) and showed no signs of progression at the end of CT . Patients were r and omly assigned to maintenance erlotinib 150 mg orally daily for 2 years or to observation . EGFR immunohistochemistry ( IHC ) , fluorescent in situ hybridization ( FISH ) , and mutation analyses were performed in 318 patients . RESULTS Between October 2005 and February 2008 , 835 patients were r and omly assigned ( median follow-up , 51 months ) . Twenty-six percent of the patients stopped erlotinib as a result of adverse effects ( of these , 67 % were due to rash ) . For erlotinib and observation , respectively , the median progression-free survival was 12.7 and 12.4 months ( hazard ratio [ HR ] , 1.05 ; 95 % CI , 0.90 to 1.23 ) , and the median overall survival was 50.8 and 59.1 months ( HR , 0.99 ; 95 % CI , 0.81 to 1.20 months ) , respectively . No subgroup could be identified with improved effect of erlotinib , based on IHC or FISH for EGFR , or mutations in genes related to the EGFR pathway , or on rash during erlotinib therapy . However , patients with a positive FISH EGFR score had a worse overall survival ( 46.1 months ) than those with a negative score ( 67.0 months ; HR , 1.56 ; 95 % CI , 1.01 to 2.40 ; P = .044 ) . Global health/ quality -of-life scores showed a significant difference during the first year ( P = .0102 ) in favor of the observation arm . CONCLUSION Maintenance erlotinib after first-line treatment in ovarian cancer did not improve progression-free or overall survival PURPOSE This phase II trial assessed the activity and tolerability of an oral dose of imatinib mesylate 400 mg twice daily in patients with recurrent or persistent epithelial ovarian or primary peritoneal carcinoma . The association between the expression of certain markers and clinical outcome was investigated . PATIENTS AND METHODS Primary measure of clinical efficacy was progression-free survival ( PFS ) at 6 months . Mutational analysis of KIT , immunohistochemistry ( IHC ) and enzyme-linked immunosorbent assay for markers ( KIT , platelet-derived growth factor [ PDGF ] receptor [ -R ] , AKT2 , phosphorylated AKT [ p-AKT ] , stem cell factor [ SCF ] , and PDGF ) were performed . RESULTS Fifty-six eligible patients were evaluated . Nine patients were progression free for at least 6 months including one complete responder . The median PFS and survival were 2 and 16 months , respectively . The most common grade 3 and 4 toxicities were neutropenia , GI , dermatologic effects , pain , and electrolyte disturbances . At least one target of imatinib ( KIT , PDGFR-alpha , or PDGFR-beta ) was expressed in all tumors , and most tumors expressed all three receptors . Higher expression of p-AKT and PDGFR-beta were associated with shorter PFS , and higher IHC scores ( % immunopositive cells x staining intensity ) of SCF and p-AKT were associated with decreased overall survival . No sequence mutations were detected in the KIT gene . Higher pretreatment plasma concentrations of PDGF-AB , PDGF-BB , and vascular endothelial growth factor ( VEGF ) were individually associated with shorter PFS and survival . CONCLUSION Imatinib mesylate was well tolerated but had minimal single-agent activity in patients with recurrent ovarian or primary peritoneal carcinoma . No marker was identified that would predict activity of imatinib ; however , tumor p-AKT and plasma VEGF levels were associated with poor outcome OBJECTIVES Approximately 50 % of ovarian cancers have elevated levels of epidermal growth factor receptor ( EGFR ) which correlates with a poor prognosis . Pre clinical evidence suggests that EGFR tyrosine kinase inhibitors ( TKIs ) , such as erlotinib ( OSI-774 ) , may potentiate the anti-tumour effects of cytotoxic agents , including carboplatin . Blocking EGFR could thus potentially reverse drug resistance . The primary objective of the study was to assess the response rate to the addition of erlotinib in patients with recurrent ovarian cancer who were receiving carboplatin .  METHODS Patients enrolled on this study had either local or advanced recurrent ovarian cancer with measurable disease . They may have had up to 2 prior chemotherapy regimens , one of which must have contained  platinum  , and they must have responded to prior platinum therapy . Patients were stratified by platinum sensitivity and were treated with erlotinib 150 mg daily on a continuous dosing schedule , and carboplatin at an AUC of 5 every 21 days . RESULTS Fifty patients with recurrent ovarian cancer entered the study , 33 in the platinum-sensitive arm and 17 in the platinum-resistant arm . Of patients evaluable for response , there were 14 partial responses ( PR ) of 30 evaluable for response ( 57 % objective response rate ( ORR ) ) in the platinum-sensitive arm , and 1 PR of 14 evaluable for response ( 7 % ORR ) in the platinum-resistant arm . CONCLUSIONS The combination of erlotinib and carboplatin was active in patients with platinum-sensitive disease , but not in platinum-resistant disease . The toxicities seen were those expected with carboplatin and erlotinib BACKGROUND Inhibition of angiogenesis is a valuable treatment strategy for ovarian cancer . Pazopanib is an anti-angiogenic drug active in ovarian cancer . We assessed the effect of adding pazopanib to paclitaxel for patients with platinum-resistant or platinum-refractory advanced ovarian cancer . METHODS We did this open-label , r and omised phase 2 trial at 11 hospitals in Italy . We included patients with platinum-resistant or platinum-refractory ovarian cancer previously treated with a maximum of two lines of chemotherapy , Eastern Cooperative Oncology Group performance status 0 - 1 , and no residual peripheral neurotoxicity . Patients were r and omly assigned ( 1:1 ) to receive weekly paclitaxel 80 mg/m(2 ) with or without pazopanib 800 mg daily , and stratified by centre , number of previous lines of chemotherapy , and platinum-free interval status . The primary endpoint was progression-free survival , assessed in the modified intention-to-treat population . This trial is registered with Clinical Trials.gov , number NCT01644825 . This report is the final analysis ; the trial is completed . FINDINGS Between Dec 15 , 2010 , and Feb 8 , 2013 , we enrolled 74 patients : 37 were r and omly assigned to receive paclitaxel and pazopanib and 37 were r and omly assigned to receive paclitaxel only . One patient , in the paclitaxel only group , withdrew from the study and was excluded from analyses . Median follow-up was 16·1 months ( IQR 12·5 - 20·8 ) . Progression-free survival was significantly longer in the pazopanib plus paclitaxel group than in the paclitaxel only group ( median 6·35 months [ 95 % CI 5·36 - 11·02 ] vs 3·49 months [ 2·01 - 5·66 ] ; hazard ratio 0·42 [ 95 % CI 0·25 - 0·69 ] ; p=0·0002 ) . We recorded no unexpected toxic effects or deaths from toxic effects . Adverse events were more common in the pazopanib and paclitaxel group than in the paclitaxel only group . The most common grade 3 - 4 adverse events were neutropenia ( 11 [ 30 % ] in the pazopanib group vs one [ 3 % ] in the paclitaxel group ) , fatigue ( four [ 11 % ] vs two [ 6 % ] ) , leucopenia ( four [ 11 % ] vs one [ 3 % ] ) , hypertension ( three [ 8 % ] vs none [ 0 % ] ) , raised aspartate aminotransferase or alanine aminotransferase ( three [ 8 % ] vs none ) , and anaemia ( two [ 5 % ] vs five [ 14 % ] ) . One patient in the pazopanib group had ileal perforation . INTERPRETATION Our findings suggest that a phase 3 study of the combination of weekly paclitaxel plus pazopanib for patients with platinum-resistant or platinum-refractory advanced ovarian cancer is warranted . FUNDING National Cancer Institute of Napoli and GlaxoSmithKline BACKGROUND V and etanib is an oral tyrosine kinase inhibitor of VEGFR-2/3 , EGFR and RET , which has demonstrated clinical activity as a single agent and in combination with taxanes . We explored the efficacy , safety and toxicity of docetaxel and v and etanib in women with recurrent ovarian cancer ( OC ) . METHODS Women with refractory or progressive OC were r and omised 1:1 to docetaxel ( 75 mg/m(2 ) , IV)+v and etanib ( 100 mg daily , PO , D+V ) or docetaxel ( 75 mg/m(2 ) , D ) . Up to three additional cytotoxic regimens for recurrence and prior anti-angiogenic agents ( as primary therapy ) were allowed . The primary end-point was progression free survival ( PFS ) . The study had 84 % power to detect a PFS hazard ratio of 0.65 , using a one-sided P of 0.1 . This corresponds to an increase in median PFS from 3.6 months to 5.6 months . Patients progressing on D were allowed to receive single agent v and etanib ( D → V ) . RESULTS 131 Patients were enrolled ; two were excluded . 16 % had received prior anti-angiogenic therapy . The median PFS estimates were 3.0 mos ( D+V ) versus 3.5 ( D ) ; HR : 0.99 ( 80 % CI : 0.79 - 1.26 ) . 61 Patients on D+V were assessable for toxicity ; 20(33 % ) had treatment-related Grade ( G ) 4 events , primarily haematologic . Similarly , 17 ( 27 % ) of 64 patients receiving D had G4 events , primarily haematologic . 27 Evaluable patients crossed-over to V. 1/27(4 % ) experienced a G4 event . G3 diarrhoea was observed in 4 % D → V patients . Median OS was 14 mos ( D+V ) versus 18 mos ( D → V ) ; HR(OS ) : 1.25 ( 80 % CI : 0.93 - 1.68 ) . Crossover v and etanib  response was 4 % ( 1/27 evaluable patients ) . High plasma IL-8 levels were associated with response to D+V. CONCLUSIONS Combination docetaxel+v and etanib did not prolong PFS relative to docetaxel alone in OC patients . No unexpected safety issues were identified OBJECTIVES Pre clinical data suggest an important role for the sarcoma proto-oncogene tyrosine kinase ( SRC ) in the oncogenesis of epithelial ovarian cancer ( EOC ) or primary peritoneal carcinoma ( PPC ) . The Gynecologic Oncology Group ( GOG ) conducted a Phase II trial to evaluate the efficacy and safety of dasatinib , an oral SRC-family inhibitor in EOC/PPC , and explored biomarkers for possible association with clinical outcome . METHODS Eligible women had measurable , recurrent or persistent EOC/PPC and had received one or two prior regimens which must have contained a platinum and a taxane . Patients were treated with 100 mg orally daily of dasatinib continuously until progression of disease or adverse effects prevented further treatment . Primary endpoints were progression-free survival (PFS)≥6months and response rate . Serial plasma sample s were assayed for multiple biomarkers . Circulating free DNA was quantified as were circulating tumor and endothelial cells . RESULTS Thirty-five ( 35 ) patients were enrolled in a two-stage sequential design . Of the 34 eligible and evaluable patients , 20.6 % ( 90 % confidence interval : 10.1 % , 35.2 % ) had a PFS≥6months ; there were no objective responses . Grade 3 - 4 toxicities were gastrointestinal ( mostly nausea and emesis ; n=4 ) , pulmonary ( dyspnea and /or pleural effusion ; n=4 
    Output:
    
The most promising results were noted with  cediranib , nintedanib , and pazopanib .