***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: We investigated the putative benefits of simultaneous teleradiotherapy and anti-epidermal growth factor receptor ( EGFR ) 125I monoclonal antibody ( MAb ) 425 radioimmunotherapy , when applied after neurosurgery in high- grade gliomas , over teleradiotherapy alone . In comparison to previous studies which have reported good results with this type of radioimmunotherapy , we advanced the adjuvant radioimmunotherapy step , that is , gave it during , not after , teleradiotherapy . The r and omized prospect i ve study examined two groups : simultaneous postoperative teleradiotherapy and radioimmunotherapy ( TRT + RIT ; eight patients ) versus teleradiotherapy alone ( TRT ; 10 patients ) . Patients who after primary operation of grade III ( 6 cases ) or IV glioma ( 12 cases ) , showed no or less than 2 mL of remnant tumor on post-operative magnetic resonance ( MR ) study and were not treated postoperatively by chemotherapy were enrolled and r and omized . Anti-EGFR 125IMAb 425 RIT was started during week 4 of radiotherapy , not later than 8 weeks after neurosurgery , and was repeated three times at 1-week intervals . Total activity given was 5026 + 739 MBq/patient . The tolerance of TRT was good . No immediate side effects of concomitant anti-EGRF 125I RIT were observed . Observation showed a median total survival ( as evaluated from the primary neurosurgical treatment ) of 14 months ( range 3.5 - 28 months ) . There was no improvement in disease-free or total survival in the group of patients treated by TRT + RIT after neurosurgery . In addition , an immunohistochemical analysis of EGFR expression in gliomas was performed in a group of 100 cases and was distinctly positive in 50 % grade IV gliomas and 68 % grade III gliomas . We conclude that simultaneous radiotherapy and radioimmunotherapy with anti-EGFR 125I-MAb 425 is not beneficial over radiotherapy alone in adjuvant treatment of high- grade gliomas after neurosurgery . We also recommend individual confirmation of EGFR expression in further anti-EGFR radioimmunotherapy trials PURPOSE Approximately 50 % of glioblastomas ( GBMs ) are characterized by overexpression of the epidermal growth factor receptor ( EGFR ) and EGFR gene amplification . In approximately 25 % of instances , constitutively activated EGFR mutants are present . These observations make EGFR-inhibiting drugs a logical approach for trials in recurrent GBM . PATIENTS AND METHODS In a r and omized , controlled , phase II trial , 110 patients with progressive GBM after prior radiotherapy were r and omly assigned to either erlotinib or a control arm that received treatment with either temozolomide or carmustine ( BCNU ) . The primary end point was 6-month progression-free survival ( PFS ) . Tumor specimens obtained at first surgery were investigated for EGFR expression ; EGFRvIII mutants ; EGFR amplification ; EGFR mutations in exons 18 , 19 , and 21 ; and pAkt . These results were correlated with outcome . Pharmacokinetic analysis was part of the study . RESULTS ; Treatment was well tolerated in general ; skin toxicity was the most frequent adverse effect of erlotinib . The 6-month PFS rate in the erlotinib arm was 11.4 % ( 95 % CI , 4.6 % to 21.5 % ) , and it was 24 % in the control arm . Of all explored biomarkers , only low pAkt expression appeared to be of borderline significance to an improved outcome . None of the eight patients who had tumors with EGFRvIII mutant presence and PTEN expression had 6-month PFS . The use of enzyme-inducing anticonvulsants significantly increased erlotinib clearance , but pharmacokinetic findings were not related to outcome . CONCLUSION Erlotinib has insufficient single-agent activity in unselected GBM . No clear biomarker associated with improved outcome to erlotinib was identified BACKGROUND Previous , uncontrolled studies have suggested that first-line treatment with gefitinib would be efficacious in selected patients with non-small-cell lung cancer . METHODS In this phase 3 , open-label study , we r and omly assigned previously untreated patients in East Asia who had advanced pulmonary adenocarcinoma and who were nonsmokers or former light smokers to receive gefitinib ( 250 mg per day ) ( 609 patients ) or carboplatin ( at a dose calculated to produce an area under the curve of 5 or 6 mg per milliliter per minute ) plus paclitaxel ( 200 mg per square meter of body-surface area ) ( 608 patients ) . The primary end point was progression-free survival . RESULTS The 12-month rates of progression-free survival were 24.9 % with gefitinib and 6.7 % with carboplatin-paclitaxel . The study met its primary objective of showing the noninferiority of gefitinib and also showed its superiority , as compared with carboplatin-paclitaxel , with respect to progression-free survival in the intention-to-treat population ( hazard ratio for progression or death , 0.74 ; 95 % confidence interval [ CI ] , 0.65 to 0.85 ; P<0.001 ) . In the subgroup of 261 patients who were positive for the epidermal growth factor receptor gene ( EGFR ) mutation , progression-free survival was significantly longer among those who received gefitinib than among those who received carboplatin-paclitaxel ( hazard ratio for progression or death , 0.48 ; 95 % CI , 0.36 to 0.64 ; P<0.001 ) , whereas in the subgroup of 176 patients who were negative for the mutation , progression-free survival was significantly longer among those who received carboplatin-paclitaxel ( hazard ratio for progression or death with gefitinib , 2.85 ; 95 % CI , 2.05 to 3.98 ; P<0.001 ) . The most common adverse events were rash or acne ( in 66.2 % of patients ) and diarrhea ( 46.6 % ) in the gefitinib group and neurotoxic effects ( 69.9 % ) , neutropenia ( 67.1 % ) , and alopecia ( 58.4 % ) in the carboplatin-paclitaxel group . CONCLUSIONS Gefitinib is superior to carboplatin-paclitaxel as an initial treatment for pulmonary adenocarcinoma among nonsmokers or former light smokers in East Asia . The presence in the tumor of a mutation of the EGFR gene is a strong predictor of a better outcome with gefitinib . ( Clinical Trials.gov number , NCT00322452 . Background The purpose of this study was to determine the maximum tolerated dose ( MTD ) , recommended phase II dose ( RPTD ) , safety , and pharmacokinetics of ABT-414 plus radiation and temozolomide in newly diagnosed glioblastoma .  ABT-414 is a first-in-class , tumor-specific antibody-drug conjugate that preferentially targets tumors expressing overactive epidermal growth factor receptor ( EGFR ) . Methods In this multicenter phase I study , patients received 0.5 - 3.2 mg/kg ABT-414  every 2 weeks by intravenous infusion . EGFR alterations , O6-methylguanine-DNA methyltransferase ( MGMT ) promoter hypermethylation , and isocitrate dehydrogenase ( IDH1 ) gene mutations were assessed in patient tumors . Distinct prognostic classes were assigned to patients based on a Molecular Classification Predictor model . Results As of January 7 , 2016 , forty-five patients were enrolled to receive  ABT-414 plus radiation and temozolomide . The most common treatment emergent adverse events were ocular : blurred vision , dry eye , keratitis , photophobia , and eye pain . Ocular toxicity at any grade occurred in 40 patients and at grade s 3/4 in 12 patients . RPTD and MTD were set at 2 mg/kg and 2.4 mg/kg , respectively . Among 38 patients with pretreatment tumor tested central ly , 39 % harbored EGFR amplification , of which 73 % had EGFRvIII mutation . Among patients with available tumor tissue ( n = 30 ) , 30 % showed MGMT promoter methylation and none had IDH1 mutations . ABT-414 demonstrated an approximately dose proportional pharmacokinetic profile . The median duration of progression-free survival was 6.1 months ; median overall survival has not been reached . Conclusion ABT-414 plus chemoradiation demonstrated an acceptable safety and pharmacokinetic profile in newly diagnosed glioblastoma . R and omized studies are ongoing to determine efficacy in newly diagnosed ( NCT02573324 ) and recurrent glioblastoma ( NCT02343406 ) BACKGROUND Survival outcomes for patients with glioblastoma remain poor , particularly for patients with unmethylated O(6)-methylguanine-DNA methyltransferase ( MGMT ) gene promoter . This phase II , r and omized , open-label , multicenter trial investigated the efficacy and safety of 2 dose regimens of the selective integrin inhibitor cilengitide combined with st and ard chemoradiotherapy in patients with newly diagnosed glioblastoma and an unmethylated MGMT promoter . METHODS Overall , 265 patients were r and omized ( 1:1:1 ) to st and ard cilengitide ( 2000 mg 2 × /wk ; n = 88 ) , intensive cilengitide ( 2000 mg 5 × /wk during wk 1 - 6 , thereafter 2 × /wk ; n = 88 ) , or a control arm ( chemoradiotherapy alone ; n = 89 ) . Cilengitide was administered intravenously in combination with daily temozolomide ( TMZ ) and concomitant radiotherapy ( RT ; wk 1 - 6 ) , followed by TMZ maintenance therapy ( TMZ/RT→TMZ ) . The primary endpoint was overall survival ; secondary endpoints included progression-free survival , pharmacokinetics , and safety and tolerability . RESULTS Median overall survival was 16.3 months in the st and ard cilengitide arm ( hazard ratio [ HR ] , 0.686 ; 95 % CI : 0.484 , 0.972 ; P = .032 ) and 14.5 months in the intensive cilengitide arm ( HR , 0.858 ; 95 % CI : 0.612 , 1.204 ; P = .3771 ) versus 13.4 months in the control arm . Median progression-free survival assessed per independent review committee was 5.6 months ( HR , 0.822 ; 95 % CI : 0.595 , 1.134 ) and 5.9 months ( HR , 0.794 ; 95 % CI : 0.575 , 1.096 ) in the st and ard and intensive cilengitide arms , respectively , versus 4.1 months in the control arm . Cilengitide was well tolerated . CONCLUSIONS St and ard and intensive cilengitide dose regimens were well tolerated in combination with TMZ/RT→TMZ . Inconsistent overall survival and progression-free survival outcomes and a limited sample size did not allow firm conclusions regarding clinical efficacy in this exploratory phase II study Background The prognosis of patients bearing high grade glioma remains dismal . Epidermal Growth Factor Receptor ( EGFR ) is well vali date d as a primary contributor of glioma initiation and progression . Nimotuzumab is a humanized monoclonal antibody that recognizes the EGFR extracellular domain and reaches Central Nervous System tumors , in non clinical and clinical setting . While it has similar activity when compared to other anti-EGFR antibodies , it does not induce skin toxicity or hypomagnesemia . Methods A r and omized , double blind , multicentric clinical trial was conducted in high grade glioma patients ( 41 anaplastic astrocytoma and 29 glioblastoma multiforme ) that received radiotherapy plus nimotuzumab or placebo .  Treatment and placebo groups were well-balanced for the most important prognostic variables . Patients received 6 weekly doses of 200 mg nimotuzumab or placebo together with irradiation as induction therapy . Maintenance treatment was given for 1 year with subsequent doses administered every 3 weeks . The objectives of this study were to assess the comparative overall survival , progression free survival , response rate , immunogenicity and safety . Results The median cumulative dose was 3200 mg of nimotuzumab given over a median number of 16 doses . The combination of nimotuzumab and RT was well-tolerated . The most prevalent related adverse reactions included nausea , fever , tremors , anorexia and hepatic test alteration . No anti-idiotypic response was detected , confirm 
    Output:
    
In summary , there is no evidence of a demonstrable overall survival benefit with the addition of anti-EGFR therapy in first-line and recurrent glioblastomas .