***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: Objective : A phase II study was performed to evaluate the efficacy and tolerability of bevacizumab and erlotinib in advanced hepatocellular carcinoma ( HCC ) patients , and to investigate clinical and molecular predictors of outcome . Methods : 59 patients with advanced HCC received 10 mg/kg i.v . of bevacizumab every 14 days and 150 mg p.o . of erlotinib daily . The primary endpoint was progression-free survival ( PFS ) at 16 weeks . Clinical characteristics and plasma biomarkers expression levels were analyzed . Results : PFS at 16 weeks was 64 % ( 95 % CI 51–76 ) : 14 patients achieved partial response ( 24 % ) , 33 had stable disease ( 56 % ) , 6 progressed ( 10 % ) , and 6 were not evaluable ( 10 % ) . Median overall survival was 13.7 months ( 95 % CI 9.6–19.7 ) , and median PFS was 7.2 months ( 95 % CI 5.6–8.3 ) . Grade 3–4 adverse events included fatigue ( 30 % ) , diarrhea ( 17 % ) , hypertension ( 14 % ) , elevated transaminases ( 12 % ) , and gastrointestinal hemorrhage ( 10 % ) . High plasma angiopoietin-2 , epidermal growth factor receptor , and endothelin-1 , and lack of acneiform rash were associated with poor outcome . Conclusions : The combination of bevacizumab with erlotinib achieved encouraging results in patients with advanced HCC . Current correlatives may help to guide future HCC studies Purpose : Vali date d biomarkers of prognosis and response to drug have not been identified for patients with hepatocellular carcinoma ( HCC ) . One of the objectives of the phase III , r and omized , controlled Sorafenib HCC Assessment R and omized Protocol ( SHARP ) trial was to explore the ability of plasma biomarkers to predict prognosis and therapeutic efficacy . Experimental Design : In SHARP , 602 patients with advanced HCC were r and omized to receive either oral sorafenib 400 mg twice a day per os or matching placebo daily on a continuous basis . Ten plasma biomarkers implicated in the pathogenesis of HCC were measured in 491 patients at baseline and in 305 after 12 weeks of treatment . The c and i date biomarkers were analyzed to identify correlates of prognosis or predictors of response to sorafenib . Results : In both the entire patient population and the placebo cohort , baseline angiopoietin 2 ( Ang2 ) and VEGF concentrations independently predicted survival . Clinical variables such as macroscopic vascular invasion , Eastern Cooperative Oncology Group ( ECOG ) performance status , and baseline α-fetoprotein and alkaline phosphatase concentrations also independently predicted survival in these groups . In the sorafenib cohort , trends toward enhanced survival benefit from sorafenib were observed in patients with high s-c-KIT or low hepatocyte growth factor concentration at baseline ( P of interaction = 0.081 and 0.073 , respectively ) . Conclusions : The angiogenesis biomarkers Ang2 and VEGF were independent predictors of survival in patients with advanced HCC . In contrast , none of the biomarkers tested significantly predicted response to sorafenib . Clin Cancer Res ; 18(8 ) ; 2290–300 . © 2012 AACR BACKGROUND The growing availability of active agents makes the development of novel therapies increasingly complex and the choice of end points critical . We assessed the frequency of use of efficacy end points in advanced breast cancer . METHODS We search ed PubMed for r and omized trials published between 2000 and 2007 in 10 leading medical journals . We abstract ed data on  progression-free survival ( PFS ) , time to tumor progression ( TTP ) , response rate ( RR ) and overall survival .  RESULTS A total of 58 studies enrolled 23,371 assessable patients in 122 treatment arms . The primary end points most frequently used were RR and TTP ( n=21 each ) , followed by PFS ( n=14 ) . In five of the trials using TTP as the primary end point , no definition of TTP was reported ; in 13 of the other 16 cases , death was counted as an event , making TTP indistinguishable from PFS . Trials having PFS , TTP or time to treatment failure as the primary end point ( n=36 ) had a higher mean number of patients than those using RR ( P=0.061 ) . CONCLUSION Investigators seem to be frequently using PFS and TTP interchangeably in advanced breast cancer . Such use of terms may lead to confusion when results of different trials are compared , and uniform use of definitions seems in order Epidermal growth factor receptor ( EGFR ) and vascular endothelial growth factor ( VEGF ) are rational targets for therapy in hepatocellular cancer ( HCC ) PURPOSE To compare the clinical outcomes of sorafenib plus either erlotinib or placebo in patients with advanced hepatocellular carcinoma ( HCC ) in a multicenter , multinational , r and omized , phase III trial . PATIENTS AND METHODS Patients with advanced HCC and underlying Child-Pugh class A cirrhosis , who were naive to systemic treatment ( N = 720 ) , were r and omly assigned to sorafenib plus either erlotinib ( n = 362 ) or placebo ( n = 358 ) . The primary end point was overall survival ( OS ) . RESULTS Median OS was similar in the sorafenib plus erlotinib and sorafenib plus placebo groups ( 9.5 v 8.5 months , respectively ; hazard ratio [ HR ] , 0.929 ; P = .408 ) , as was median time to progression ( 3.2 v 4.0 months , respectively ; HR , 1.135 ; P = .18 ) . In the sorafenib/erlotinib arm versus the sorafenib/placebo arm , the overall response rate trended higher ( 6.6 % v 3.9 % , respectively ; P = .102 ) , whereas the disease control rate was significantly lower ( 43.9 % v 52.5 % , respectively ; P = .021 ) . The median duration s of treatment with sorafenib were 86 days in the sorafenib/erlotinib arm and 123 days in the sorafenib/placebo arm . In the sorafenib/erlotinib and sorafenib/placebo arms , the rates of treatment-emergent serious AEs ( 58.0 % v 54.6 % , respectively ) and drug-related serious AEs ( 21.0 % v 22.8 % , respectively ) were similar . AEs matched the known safety profiles of both agents , but rates of rash/desquamation , anorexia , and diarrhea were higher in the sorafenib/erlotinib arm , whereas rates of alopecia and h and -foot skin reaction were higher in the sorafenib/placebo arm . Withdrawal rates for AEs during cycles 1 to 3 were higher in the sorafenib/erlotinib arm . CONCLUSION Adding erlotinib to sorafenib did not improve survival in patients with advanced HCC Growth factor overexpression , including epidermal growth factor receptor ( EGFR ) expression , is common in hepatocellular cancers . Erlotinib is a receptor tyrosine kinase inhibitor with specificity for EGFR . The primary objective of this study was to determine the proportion of hepatocellular carcinoma ( HCC ) patients treated with erlotinib who were alive and progression‐free ( PFS ) at 16 weeks of continuous treatment PURPOSE Epidermal growth factor receptor/human epidermal growth factor receptor 1 ( EGFR/HER1 ) and lig and expression is frequently seen in hepatocellular cancers ( HCCs ) . Erlotinib ( Tarceva , OSI-774 ; OSI Pharmaceuticals , Melville , NY ) is a receptor tyrosine kinase inhibitor with specificity for the EGFR/HER1 . METHODS The primary objective of this study was to determine the proportion of patients with advanced HCC who were progression-free at 6 months . Patients with either unresectable or metastatic disease were studied . Only one prior systemic or locoregional therapy was allowed . Erlotinib was given continuously at a dose of 150 mg per day orally . RESULTS Thirty-eight patients with HCC were enrolled . Median age of the patients was 69 years ( range , 27 to 83 years ) . A majority of patients ( 63 % ) had an Eastern Cooperative Oncology Group performance status of 1 . Forty-seven percent of patients had received prior chemotherapy for advanced HCC . EGFR/HER1 expression was detected in 88 % of the patients . Median number of cycles per patient was two ( range , 1 to 26 ) . Twelve ( 32 % ; CI 95 % , 18 to 49 ) of the 38 patients with HCC were progression-free at 6 months . Three patients had partial radiologic responses of duration of 2 , 10 , and 11 months , respectively . Disease control was seen in 59 % of the patients . Median overall survival time was 13 months . Ten patients ( 26 % ) had toxicity-related dose reductions of erlotinib . Grade 3/4 skin toxicity or diarrhea was encountered in five and three patients , respectively . CONCLUSION Results of this trial suggest a benefit for EGFR/HER1 blockade with erlotinib in patients with HCC manifested by disease control . Additional studies with erlotinib as a single agent or in combination with other agents are warranted PURPOSE The study objective was to determine the proportion of patients with hepatocellular carcinoma ( HCC ) treated with the combination of bevacizumab ( B ) and erlotinib ( E ) who were alive and progression free at 16 weeks ( 16-week progression-free survival [ PFS16 ] ) of continuous therapy . Secondary objectives included response rate , median PFS , survival , and toxicity . PATIENTS AND METHODS Patients who had advanced HCC that was not amenable to surgical or regional therapies , up to one prior systemic treatment ; Childs-Pugh score A or B liver function ; Eastern Cooperative Oncology Group performance status 0 , 1 , or 2 received B 10 mg/kg every 14 days and E 150 mg orally daily , continuously , for 28-day cycles . Tumor response was evaluated every 2 cycles by using Response Evaluation Criteria in Solid Tumors Group criteria . A total of 40 patients were treated . RESULTS The primary end point of PFS16 was 62.5 % . Ten patients achieved a partial response for a confirmed overall response rate ( intent-to-treat ) of 25 % . The median PFSevent was 39 weeks ( 95 % CI , 26 to 45 weeks ; 9.0 months ) , and the median overall survival was 68 weeks ( 95 % CI , 48 to 78 weeks ; 15.65 months ) . Grade s 3 to 4 drug-related toxicity included fatigue ( n = 8 ; 20 % ) , hypertension ( n = 6 ; 15 % ) , diarrhea ( n = 4 ; 10 % ) elevated transaminases ( n = 4 ; 10 % ) , gastrointestinal hemorrhage ( n = 5 ; 12.5 % ) , wound infection ( n = 2 ; 5 % ) thrombocytopenia ( n = 1 ; 2.5 % ) , and proteinuria , hyperbilirubinemia , back pain , hyperkalemia , and anorexia ( n = 1 each ) . CONCLUSION The combination of B + E in patients who had advanced HCC showed significant , clinical ly meaningful antitumor activity . B + E warrant additional evaluation in r and omized controlled trials BACKGROUND Patients with advanced hepatocellular ( HCC ) and biliary tract carcinomas ( BTC ) have poor prognosis . While the EGFR pathway is overactive in HCC and BTC , single agent anti-EGFR therapies confer modest activity . Pre clinical data showed synergistic antiproliferative and proapoptotic effects between anti-EGFR therapies and taxanes . We conducted a phase I study of erlotinib and docetaxel in solid tumors , and noted good tolerability and sustained complete ( 5 years + ) and partial responses in patients with HCC and BTC . This trial evaluated the efficacy of erlotinib with docetaxel in refractory hepatobiliary cancers . METHODS Eligible patients were allowed to have two prior systemic therapies .  Docetaxel 30 mg/m2 i.v . was administered on days 1 , 8 , 15 , and erlotinib 150 mg was dosed orally on days 2 - 7 , 9 - 14 , 16 - 28 of each 28-day cycle . The primary endpoint was 16 weeks progression-free survival ( PFS ) , and secondary endpoints included response , stable disease , and overall survival . Tumor sample s were analyzed for KRAS gene mutations and E-cadherin expression by immunohistochemistry ( IHC ) . Patients with BTC and HCC were accrued and assessed in separate strata for the efficacy endpoints , but for the two-stage initial design of the study , combined PFS was considered . A Simon optimal two-stage design tested the hypothesis that the 16-week PFS is ≤ 15 % ( clinical ly inactive ) versus the alternative of ≥  
    Output:
    
Conclusion : Erlotinib provides efficacious and well-tolerated treatment for advanced HCC .