***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: Background Anti-angiogenic treatment is believed to have at least cystostatic effects in highly vascularized tumours like pancreatic cancer . In this study , the treatment effects of the angiogenesis inhibitor Cilengitide and gemcitabine were compared with gemcitabine alone in patients with advanced unresectable pancreatic cancer . Methods A multi-national , open-label , controlled , r and omized , parallel-group , phase II pilot study was conducted in 20 centers in 7 countries .  Cilengitide was administered at 600 mg/m2 twice weekly for 4 weeks per cycle and gemcitabine at 1000 mg/m2 for 3 weeks followed by a week of rest per cycle . The planned treatment period was 6 four-week cycles . The primary endpoint of the study was overall survival and the secondary endpoints were progression-free survival ( PFS ) , response rate , quality of life ( QoL ) , effects on biological markers of disease ( CA 19.9 ) and angiogenesis ( vascular endothelial growth factor and basic fibroblast growth factor ) , and safety . An ancillary study investigated the pharmacokinetics of both drugs in a subset of patients . Results Eighty-nine patients were r and omized . The median overall survival was 6.7 months for Cilengitide and gemcitabine and 7.7 months for gemcitabine alone . The median PFS times were 3.6 months and 3.8 months , respectively . The overall response rates were 17 % and 14 % , and the tumor growth control rates were 54 % and 56 % , respectively . Changes in the levels of CA 19.9 went in line with the clinical course of the disease , but no apparent relationships were seen with the biological markers of angiogenesis . QoL and safety evaluations were comparable between treatment groups . Pharmacokinetic studies showed no influence of gemcitabine on the pharmacokinetic parameters of Cilengitide and vice versa . Conclusion There were no clinical ly important differences observed regarding efficacy , safety and QoL between the groups . The observations lay in the range of other clinical studies in this setting . The combination regimen was well tolerated with no adverse effects on the safety , tolerability and pharmacokinetics of either agent PURPOSE To define the safety , efficacy , and pharmacogenetic and pharmacodynamic effects of sorafenib with gemcitabine-based chemoradiotherapy ( CRT ) in locally advanced pancreatic cancer . METHODS AND MATERIAL S Patients received gemcitabine 1000 mg/m(2 ) intravenously weekly × 3 every 4 weeks per cycle for 1 cycle before CRT and continued for up to 4 cycles after CRT . Weekly gemcitabine 600 mg/m(2 ) intravenously was given during concurrent intensity modulated radiation therapy of 50 Gy to gross tumor volume in 25 fractions . Sorafenib was dosed orally 400 mg twice daily until progression , except during CRT when it was escalated from 200 mg to 400 mg daily , and 400 mg twice daily . The maximum tolerated dose cohort was exp and ed to 15 patients . Correlative studies included dynamic contrast-enhanced MRI and angiogenesis genes polymorphisms ( VEGF-A and VEGF-R2 single nucleotide polymorphisms ) . RESULTS Twenty-seven patients were enrolled . No dose-limiting toxicity occurred during induction gemcitabine/sorafenib followed by concurrent CRT . The most common grade 3/4 toxicities were fatigue , hematologic , and gastrointestinal . The maximum tolerated dose was sorafenib 400 mg twice daily . The median progression-free survival and overall survival for 25 evaluable patients were 10.6 and 12.6 months , respectively . The median overall survival for patients with VEGF-A -2578 AA , -1498 CC , and -1154 AA versus alternate genotypes was 21.6 versus 14.7 months . Dynamic contrast-enhanced MRI demonstrated higher baseline K(trans ) in responding patients . CONCLUSIONS Concurrent sorafenib with CRT had modest clinical activity with increased gastrointestinal toxicity in localized unresectable pancreatic cancer . Select VEGF-A/VEGF-R2 genotypes were associated with favorable survival Gemcitabine is a key drug for the treatment of pancreatic cancer ; however , with its limitation in clinical benefits , the development of another potent therapeutic is necessary . Vascular endothelial growth factor receptor 2 is an essential target for tumor angiogenesis , and we have conducted a phase I clinical trial using gemcitabine and vascular endothelial growth factor receptor 2 peptide ( elpamotide ) . Based on the promising results of this phase I trial , a multicenter , r and omized , placebo‐controlled , double‐blind phase II/III clinical trial has been carried out for pancreatic cancer . The eligibility criteria included locally advanced or metastatic pancreatic cancer . Patients were assigned to either the Active group ( elpamotide + gemcitabine ) or Placebo group ( placebo + gemcitabine ) in a 2:1 ratio by the dynamic allocation method . The primary endpoint was overall survival . The Harrington – Fleming test was applied to the statistical analysis in this study to evaluate the time‐lagged effect of immunotherapy appropriately . A total of 153 patients ( Active group , n = 100 ; Placebo group , n = 53 ) were included in the analysis . No statistically significant differences were found between the two groups in the prolongation of overall survival ( Harrington – Fleming P‐value , 0.918 ; log – rank P‐value , 0.897 ; hazard ratio , 0.87 , 95 % confidence interval [ CI ] , 0.486–1.557 ) . Median survival time was 8.36 months ( 95 % CI , 7.46–10.18 ) for the Active group and 8.54 months ( 95 % CI , 7.33–10.84 ) for the Placebo group . The toxicity observed in both groups was manageable . Combination therapy of elpamotide with gemcitabine was well tolerated . Despite the lack of benefit in overall survival , subgroup analysis suggested that the patients who experienced severe injection site reaction , such as ulceration and erosion , might have better survival Objectives In mouse models of pancreatic cancer , IPI-926 , an oral Hedgehog inhibitor , increases chemotherapy delivery by depleting tumor-associated stroma . This multicenter phase Ib study evaluated IPI-926 in combination with FOLFIRINOX ( 5-fluorouracil , leucovorin , irinotecan , oxaliplatin ) in patients with advanced pancreatic cancer . Methods Patients were treated with once-daily IPI-926 plus FOLFIRINOX . A 3 + 3 dose escalation design was used , with cohort expansion at the maximum tolerated dose . A subset of patients underwent perfusion computed tomography to assess changes in tumor perfusion . Results The maximum tolerated dose was identified 1 dose level below st and ard FOLFIRINOX . Common treatment-related adverse events included liver function test abnormalities , neuropathy , nausea/vomiting , and diarrhea . Objective response rate was high ( 67 % ) , and patients receiving IPI-926 maintenance showed further declines in CA19 - 9 levels even after FOLFIRINOX discontinuation . Treatment did not result in consistent increases in tumor perfusion . The study closed early when a separate phase II trial of IPI-926 plus gemcitabine indicated detrimental effects of this combination . Conclusions This is the first study to demonstrate the feasibility of using FOLFIRINOX as the chemotherapeutic backbone in a clinical trial design . Although robust antitumor activity and acceptable safety were observed with the addition of IPI-926 to this regimen , future development of Hedgehog inhibitors in pancreatic cancer seems unlikely BACKGROUND Nivolumab , a fully human IgG4 programmed death 1 ( PD-1 ) immune-checkpoint-inhibitor antibody , disrupts PD-1-mediated signaling and may restore antitumor immunity . METHODS In this r and omized , open-label , international phase 3 study , we assigned patients with nonsquamous non-small-cell lung cancer ( NSCLC ) that had progressed during or after platinum-based doublet chemotherapy  to receive nivolumab at a dose of 3 mg per kilogram of body weight every 2 weeks or docetaxel at a dose of 75 mg per square meter of body-surface area every 3 weeks . The primary end point was overall survival . RESULTS Overall survival was longer with nivolumab than with docetaxel .  The median overall survival was 12.2 months ( 95 % confidence interval [ CI ] , 9.7 to 15.0 ) among 292 patients in the  nivolumab group and 9.4 months ( 95 % CI , 8.1 to 10.7 ) among 290 patients in the docetaxel group ( hazard ratio for death , 0.73 ; 96 % CI , 0.59 to 0.89 ; P=0.002 ) . At 1 year , the overall survival rate was 51 % ( 95 % CI , 45 to 56 ) with nivolumab versus 39 % ( 95 % CI , 33 to 45 ) with docetaxel . With additional follow-up , the overall survival rate at 18 months was 39 % ( 95 % CI , 34 to 45 ) with nivolumab versus 23 % ( 95 % CI , 19 to 28 ) with docetaxel . The response rate was 19 % with nivolumab versus 12 % with docetaxel ( P=0.02 ) . Although progression-free survival did not favor nivolumab over docetaxel ( median , 2.3 months and 4.2 months , respectively ) , the rate of progression-free survival at 1 year was higher with nivolumab than with docetaxel ( 19 % and 8 % , respectively ) . Nivolumab was associated with even greater efficacy  than docetaxel across all end points in subgroups defined according to prespecified levels of tumor-membrane expression ( ≥1 % , ≥5 % , and ≥10 % ) of the PD-1 lig and . Treatment-related adverse events of grade 3 or 4 were reported in 10 % of the patients in the nivolumab group , as compared with 54 % of those in the docetaxel group . CONCLUSIONS Among patients with advanced nonsquamous NSCLC that had progressed during or after platinum-based chemotherapy  , overall survival was longer with nivolumab than with docetaxel . ( Funded by Bristol-Myers Squibb ; CheckMate 057 Clinical Trials.gov number , NCT01673867 . ) Inoperable cancer of the exocrine pancreas responds poorly to most conventional anti-cancer agents , and new agents are required to palliate this disease . Seocalcitol ( EB1089 ) , a vitamin D analogue , can inhibit growth , induce differentiation and induce apoptosis of cancer cell lines in vitro and can also inhibit growth of pancreatic cancer xenografts in vivo . Thirty-six patients with advanced pancreatic cancer received once daily oral treatment with seocalcitol with dose escalation every 2 weeks until hypercalcaemia occurred , following which patients continued with maintenance therapy . The most frequent toxicity was the anticipated dose-dependent hypercalcaemia , with most patients tolerating a dose of 10–15 μg per day in chronic administration . Fourteen patients completed at least 8 weeks of treatment and were evaluable for efficacy , whereas 22 patients were withdrawn prior to completing 8 weeks ' treatment and in 20 of these patients withdrawal was due to clinical deterioration as a result of disease progression . No objective responses were observed , with five of 14 patients having stable disease in whom the duration of stable disease was 82–532 days ( median=168 days ) . The time to treatment failure ( n=36 ) ranged from 22 to 847 days , and with a median survival of approximately 100 days . Seocalcitol is well tolerated in pancreatic cancer but has no objective anti-tumour activity in advanced disease . Further studies are necessary to determine if this agent has any cytostatic activity in this malignancy in minimal disease states BACKGROUND Nivolumab ( a programmed death 1 [ PD-1 ] checkpoint inhibitor ) and ipilimumab ( a cytotoxic T-lymphocyte-associated antigen 4 [ CTLA-4 ] checkpoint inhibitor ) have been shown to have complementary activity in metastatic melanoma . In this r and omized , double-blind , phase 3 study , nivolumab alone or nivolumab plus ipilimumab was compared with ipilimumab alone in patients with metastatic melanoma . METHODS We assigned , in a 1:1:1 ratio , 945 previously untreated patients with unresectable stage III or IV melanoma to nivolumab alone , nivolumab plus ipilimumab , or ipilimumab alone  . Progression-free survival and overall survival were co primary end points . Results regarding progression-free survival are presented here . RESULTS The median progression-free survival was 11.5 months ( 95 % confidence interval [ CI ] , 8.9 to 16.7 ) with nivolumab plus ipilimumab , as compared with 2.9 months 
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The qualitative synthesis revealed a treatment advantage of combined therapy with nab-paclitaxel , while the meta- analysis on anti-VEGF/VEGFR drugs demonstrated marginal improvement of objective response rates and progression-free survival , but not overall survival .