***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 The treatment of advanced renal cell carcinoma has been revolutionised by targeted therapy with drugs that block angiogenesis . So far , no phase 3 r and omised trials comparing the effectiveness of one targeted agent against another have been reported . We did a r and omised phase 3 study comparing axitinib , a potent and selective second-generation inhibitor of vascular endothelial growth factor ( VEGF ) receptors , with sorafenib , an approved VEGF receptor inhibitor , as second-line therapy in patients with metastatic renal cell cancer . METHODS We included patients coming from 175 sites ( hospitals and outpatient clinics ) in 22 countries aged 18 years or older with confirmed renal clear-cell carcinoma who progressed despite first-line therapy containing sunitinib , bevacizumab plus interferon-alfa , temsirolimus , or cytokines .  Patients were stratified according to Eastern Cooperative Oncology Group performance status and type of previous treatment and then r and omly assigned ( 1:1 ) to either axitinib ( 5 mg twice daily ) or sorafenib ( 400 mg twice daily ) . Axitinib dose increases to 7 mg and then to 10 mg , twice daily , were allowed for those patients without hypertension or adverse reactions above grade 2 . Participants were not masked to study treatment . The primary endpoint was progression-free survival ( PFS ) and was assessed by a masked , independent radiology review and analysed by intention to treat . This trial was registered on Clinical Trials.gov , number NCT00678392 . FINDINGS A total of 723 patients were enrolled and r and omly assigned to receive axitinib ( n=361 ) or sorafenib ( n=362 ) . The median PFS was 6·7 months with axitinib compared to 4·7 months with sorafenib ( hazard ratio 0·665 ; 95 % CI 0·544 - 0·812 ; one-sided p<0·0001 ) . Treatment was discontinued because of toxic effects in 14 ( 4 % ) of 359 patients treated with axitinib and 29 ( 8 % ) of 355 patients treated with sorafenib . The most common adverse events were diarrhoea , hypertension , and fatigue in the axitinib arm , and diarrhoea , palmar-plantar erythrodysaesthesia , and alopecia in the sorafenib arm . INTERPRETATION Axitinib result ed in significantly longer PFS compared with sorafenib . Axitinib is a treatment option for second-line therapy of advanced renal cell carcinoma . FUNDING Pfizer BACKGROUND Sunitinib is a st and ard-of-care treatment in advanced clear cell renal cell carcinoma ( ccRCC ) . Retrospective and exp and ed access data suggest sunitinib has activity in advanced non-clear cell renal cell carcinoma ( nccRCC ) . OBJECTIVE To prospect ively determine the clinical efficacy and safety of sunitinib in patients with advanced nccRCC . DESIGN , SETTING , AND PARTICIPANTS This is a single-arm phase 2 trial with a two-stage design . Eligibility criteria included pathologically confirmed nccRCC or ccRCC with ≥ 20 % sarcomatoid histology , performance status 0 - 2 , measurable disease , a maximum of two prior systemic therapies , and no prior treatment with tyrosine kinase inhibitors directed against the vascular endothelial growth factor receptors . INTERVENTION Patients received sunitinib 50 mg daily on a 4-wk on , 2-wk off schedule . OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Primary end points were objective response rate ( ORR ) and progression-free survival ( PFS ) . Secondary end points were safety and overall survival ( OS ) . RESULTS AND LIMITATIONS Fifty-seven patients were eligible ( nccRCC histology : papillary , 27 ; chromophobe , 5 ; unclassified , 8 ; collecting duct or medullary carcinoma , 6 ; sarcomatoid , 7 ; and others , 4 )  . Median PFS for 55 evaluable patients was 2.7 mo ( 95 % confidence interval [ CI ] , 1.4 - 5.4 ) . Two patients with chromophobe and one patient with unclassified histology had a confirmed partial response ( 5 % ORR ) . Median PFS for patients with papillary histology was 1.6 mo ( 95 % CI , 1.4 - 5.4 ) . Median PFS for patients with chromophobe histology was 12.7 mo ( 95 % CI , 8.5-NA ) . Median OS for all patients was 16.8 mo ( 95 % CI , 10.7 - 26.3 ) . Treatment-emergent adverse events were consistent with sunitinib 's mechanism of action . The nonr and omized design and small number of patients are limitations of this study . CONCLUSIONS The differential response of chromophobe histology to sunitinib suggests a therapeutically relevant biological heterogeneity exists within nccRCC . The low ORR and short PFS with sunitinib in the other nccRCC subtypes underscore the need to enroll patients with these diverse tumors in clinical trials BACKGROUND We investigated the efficacy of everolimus against nonclear-cell renal cell carcinoma ( nccRCC ) . Patients and methods Patients with nccRCC received 10-mg everolimus once daily until disease progression or unacceptable toxicity . PATIENTS who had received a VEGF- tyrosine kinase inhibitor ( TKI ) previously were included . RESULTS A total of 49 patients were enrolled . Twenty-three patients ( 46.9 % ) received prior anti-VEGF agents . A partial response was observed in five patients ( 10.2 % ) and stable disease in 25 patients ( 51.0 % ) . The disease progressed in 16 patients ( 32.7 % ) despite the administration of everolimus . Two of the five patients who showed an objective response to everolimus had chromophobe carcinoma , whereas two had papillary carcinoma and one had unclassifiable carcinoma . Thirty-six patients experienced disease progression during follow-up , and the median progression-free survival ( PFS ) was 5.2 months . Chromophobe RCC patients seemed to have longer PFS than nccRCC patients with the other histological subtypes ( P = 0.084 ) . Previous VEGF-TKI treatment did not influence the efficacy of everolimus , and the toxicity profiles were in line with previous reports . CONCLUSION Everolimus shows certain efficacy against nccRCC , particularly in patients with chromophobe RCC , and prior treatment with a VEGF-TKI appears not influencing the outcome of everolimus therapy in nccRCC patients . Clinical Trials.gov number NCT00830895 Purpose : The goal of this study was to evaluate  immunohistochemical and cytogenetic features  and their prognostic value in papillary renal cell carcinoma ( PRCC ) subtypes . Experimental Design : One hundred fifty-eight cases of PRCC were identified and reclassified by subtype . Tumoral expression of 29 molecular markers was determined by immunohistochemistry . Cytogenetic analyses  were done on a prospect i ve series of 65 patients . Associations with clinicopathologic information and disease-specific survival were assessed . Results : Fifty-one patients ( 32 % ) had type 1 and 107 ( 68 % ) type 2 PRCC . Type 2 patients had worse Eastern Cooperative Oncology Group performance status , higher T stages , nodal and distant metastases , higher grade s , and a higher frequency of necrosis , collecting system invasion and sarcomatoid features . Type 2 showed greater expression of vascular endothelial growth factor (VEGF)-R2 in the tumor epithelium , and of VEGF-R3 in both tumor epithelium and endothelium . Loss of chromosome 1p , loss of 3p , and gain of 5q were exclusively observed in type 2 , whereas type 1 more frequently had trisomy 17 . Type 2 PRCC was associated with worse survival than type 1 , but type was not retained as an independent prognostic factor . Lower PTEN , lower EpCAM , lower gelsolin , higher CAIX , and higher VEGF-R2 and VEGF-R3 expression , loss of 1p , 3p , or 9p , and absence trisomy 17 were all associated with poorer prognosis . Conclusions : Type 2 PRCC is associated with more aggressive clinicopathologic features and worse outcome . Molecular and chromosomal alterations can distinguish between PRCC subtypes and influence their prognosis . The effect of 3p loss on survival in PRCC is opposite to the relationship seen in clear cell RCC PURPOSE Mature survival data and evaluation of vascular endothelial growth factor ( VEGF ) as a prognostic biomarker from the Treatment Approaches in Renal Cancer Global Evaluation Trial ( TARGET ) study in patients with renal cell carcinoma ( RCC ) are reported . PATIENTS AND METHODS Nine hundred three previously treated patients were r and omly assigned to receive sorafenib versus placebo . On demonstration of progression-free survival ( PFS ) benefit with sorafenib , patients assigned to placebo were offered sorafenib .  Overall survival ( OS ) was determined at two planned interim analyses and one final analysis , with a secondary OS analysis conducted by censoring placebo patients who crossed over to sorafenib . The relationships between baseline VEGF level and prognosis and efficacy were evaluated . RESULTS The final OS of patients receiving sorafenib was comparable with that of patients receiving placebo ( 17.8 v 15.2 months , respectively ; hazard ratio [ HR ] = 0.88 ; P = .146 ) ; however , when post-cross-over placebo survival data were censored , the difference became significant ( 17.8 v 14.3 months , respectively ; HR = 0.78 ; P = .029 ) . Adverse events at 16 months after cross over were similar to those previously reported . Baseline VEGF levels correlated with Eastern Cooperative Oncology Group performance status ( P < .0001 ) , Memorial Sloan-Kettering Cancer Center score ( P < .0001 ) , and PFS and OS in univariate ( PFS , P = .0013 ; OS , P = .0009 ) and multivariate ( PFS , P = .0231 ; OS , P = .0416 ) analyses of placebo patients and with short OS by multivariate analysis of patients receiving sorafenib ( P = .0145 ) . Both high-VEGF ( P < .01 ) and low-VEGF ( P < .01 ) groups benefited from sorafenib . CONCLUSION Although an OS benefit was not seen on a primary intent-to-treat analysis , results of a secondary OS analysis censoring placebo patients demonstrated a survival advantage for those receiving sorafenib , suggesting an important cross-over effect . VEGF levels are prognostic for PFS and OS in RCC . The results of TARGET establish the efficacy and safety of sorafenib in advanced RCC BACKGROUND Retrospective and molecular biologic data suggest that sunitinib may be effective in patients with non-clear cell renal cell carcinoma ( nccRCC ) . PATIENTS AND METHODS Eligibility criteria included advanced nccRCC except for collecting duct carcinoma and sarcomatoid carcinoma without identifiable renal cell carcinoma subtypes . Patients were treated with 50 mg/day oral sunitinib for 4 weeks , followed by 2 weeks of rest . The primary end point was overall response rate ( RR ) . RESULTS Thirty-one eligible patients were enrolled . Twenty-four patients ( 77 % ) had prior nephrectomy . By Memorial Sloan-Kettering Cancer Center criteria , 8 patients ( 26 % ) had poor risk and 14 ( 45 % ) had intermediate risk . Twenty-two patients had papillary renal cell carcinoma ( RCC ) , and three had chromophobe RCC . Eleven patients had partial response with a RR of 36 % ( 95 % confidence interval ( CI ) 19 % to 52 % ) and an additional 17 patients ( 55 % ) had stable disease . Median duration of response was 12.7 months ( 95 % CI 6.3 - 19.1 months ) , and median progression-free survival was 6.4 months ( 95 % CI 4.2 - 8.6 months ) . At a median follow-up duration of 18.7 months ( 95 % CI 13.7 - 23.7 months ) , 13 patients ( 42 % ) had died , result ing in an estimated median survival of 25.6 months ( 95 % CI 8.4 - 42.9 months ) . Toxicity profiles were commensurate with prior reports . CONCLUSIONS Sunitinib has promising activity in patients with nccRCC ( NCT01219751 ) BACKGROUND Cytotoxic chemotherapy has not been well investigated in non-clear-cell renal cell carcinoma ( RCC ) . A phase II study was thus conducted to assess the efficacy of carboplatin and paclitaxel in such patients . PATIENTS AND METHODS Patients were treated with carboplatin ( area under the curve of 6 ) and paclitaxel 225 mg/m2 every 21 days and assessed for measurable disease response every 2 cycles . An initial 20 patients were planned to be enrolled to rule 
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CONCLUSION There is insufficient evidence ( level C ) to recommend sunitinib monotherapy in advanced non clear cell RCC and the available data suggests it appears less efficacious than that in advanced clear cell RCC .