***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 We conducted a phase 2b , r and omised , double-blind , placebo-controlled screening trial to evaluate the addition of the multikinase inhibitor sorafenib ( antiproliferative/antiangiogenic ) to first-line paclitaxel for human epidermal growth factor receptor 2 (HER2)-negative locally recurrent/metastatic breast cancer . METHODS Patients were r and omised to paclitaxel ( 90mg/m(2 ) , weekly , intravenously , 3 weeks on/1 week off )  plus sorafenib ( 400 mg , orally , twice daily ) or placebo . The primary endpoint was progression-free survival ( PFS ) . A sample size of 220 patients was planned with relative risk ≤ 0.82 ( 1-sided α=0.14 ) after 120 events supporting a treatment effect . FINDINGS Patients were r and omised in India ( n=170 ) , the United States ( n=52 ) and Brazil ( n=15 ) . Median PFS was 6.9 months for sorafenib versus 5.6 months for placebo ( hazard ratio (HR)=0.788 ; 95 % confidence interval ( CI ) , 0.558 - 1.112 ; P=0.1715 [ 1-sided P=0.0857 ] ) . The addition of sorafenib increased time to progression ( median , 8.1 versus 5.6 months ; HR=0.674 ; 95 % CI 0.465 - 0.975 ; P=0.0343 ) and improved overall response ( 67 % versus 54 % ; P=0.0468 ) . Overall survival did not statistically differ ( median , 16.8 versus 17.4 months ; HR=1.022 ; 95 % CI 0.715 - 1.461 ; P=0.904 ) . Grade 3/4 toxicities ( sorafenib versus placebo ) included h and -foot skin reaction ( 31 % versus 3 % ) , neutropenia ( 13 % versus 7 % ) and anaemia ( 11 % versus 6 % ) . Two treatment-related deaths occurred ( malaria and liver dysfunction ) in the sorafenib arm . INTERPRETATION The addition of sorafenib to paclitaxel improved disease control but did not significantly improve PFS to support a phase 3 trial of similar design . Toxicity of the combination was manageable with dose reductions PURPOSE To investigate whether sunitinib plus docetaxel improves clinical outcomes for patients with human epidermal growth factor receptor 2 (HER2)/neu-negative advanced breast cancer ( ABC ) versus docetaxel alone . PATIENTS AND METHODS In this phase III study , patients were r and omly assigned to open-label combination therapy ( sunitinib 37.5 mg/d , days 2 to 15 every 3 weeks ; and docetaxel 75 mg/m(2 ) , day 1 every 3 weeks ) or monotherapy ( docetaxel 100 mg/m(2 ) every 3 weeks ) .  Progression-free survival ( PFS )  was the primary end point . RESULTS Two hundred ninety-six patients were r and omly assigned to combination therapy , and 297 patients were assigned to monotherapy .  Median PFS times were 8.6 and 8.3 months with combination therapy and monotherapy , respectively ( hazard ratio , 0.92 ; one-sided P = .265 ) . The objective response rate ( ORR ) was significantly higher with the combination ( 55 % ) than with monotherapy ( 42 % ; one-sided P = .001 ) . Duration of response was similar in both arms ( 7.5 months with the combination v 7.2 months with monotherapy ) . Median overall survival ( OS ) times were 24.8 and 25.5 months with combination therapy and monotherapy , respectively ( one-sided P = .904 ) . There were 107 deaths with the combination and 91 deaths with monotherapy . The frequency of common adverse events ( AEs ) was higher with the combination , as were treatment discontinuations caused by AEs . CONCLUSION The combination of sunitinib plus docetaxel improved ORR but did not prolong either PFS or OS compared with docetaxel alone when given to an unselected HER2/neu-negative cohort as first-line treatment for ABC . Sunitinib combination therapy may also have result ed in AEs that yield an unfavorable risk-benefit ratio . The sunitinib-docetaxel regimen evaluated in this study is not recommended for further use in ABC 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 Summary Purpose The aim of this Phase II study was to assess the efficacy and safety of v and etanib in combination with docetaxel in patients with pretreated advanced breast cancer . Methods The primary study objective was to compare the number of progression events in patients receiving once-daily oral v and etanib ( 100 mg ) in combination with docetaxel  ( 100 mg/m2 iv every 21 days ) versus placebo plus docetaxel .  Sixty-four patients were r and omized to receive study treatment ( n = 35 , v and etanib ; n = 29 , placebo ) . Results A slightly greater number of patients had experienced a progression event by the data cut-off in the v and etanib group ( 24 [ 69 % ] ) compared with the placebo group ( 18 [ 62 % ] ) ; HR = 1.19 , two-sided 80 % CI : 0.79–1.81 ; two-sided P = 0.59 ) , suggesting that the addition of v and etanib to docetaxel did not affect the risk of disease progression compared with placebo plus docetaxel .  The safety and tolerability profile of the combination therapy reflected those of both drugs as monotherapy agents . Conclusions In patients with advanced breast cancer , v and etanib plus docetaxel was generally well tolerated . Clinical benefit was not different to that observed with placebo plus docetaxel . However , due to the small patient number it was not possible to yield robust results , further research is required to identify predictive factors for patient selection Purpose : We assessed adding the multikinase inhibitor sorafenib to gemcitabine or capecitabine in patients with advanced breast cancer whose disease progressed during/after bevacizumab . Experimental Design : This double-blind , r and omized , placebo-controlled phase IIb study ( Clinical Trials.gov NCT00493636 ) enrolled patients with locally advanced or metastatic human epidermal growth factor receptor 2 (HER2)–negative breast cancer and prior bevacizumab treatment . Patients were r and omized to chemotherapy with sorafenib ( 400 mg , twice daily ) or matching placebo . Initially , chemotherapy was gemcitabine ( 1,000 mg/m2 i.v . , days 1 , 8/21 ) , but later , capecitabine ( 1,000 mg/m2 orally twice daily , days 1–14/21 ) was allowed as an alternative . The primary endpoint was progression-free survival ( PFS ) . Results : One hundred and sixty patients were r and omized . More patients received gemcitabine ( 82.5 % ) than capecitabine ( 17.5 % ) . Sorafenib plus gemcitabine/capecitabine was associated with a statistically significant prolongation in PFS versus placebo plus gemcitabine/capecitabine [ 3.4 vs. 2.7 months ; HR = 0.65 ; 95 % confidence interval ( CI ) : 0.45–0.95 ; P = 0.02 ] , time to progression was increased ( median , 3.6 vs. 2.7 months ; HR = 0.64 ; 95 % CI : 0.44–0.93 ; P = 0.02 ) , and overall response rate was 19.8 % versus 12.7 % ( P = 0.23 ) . Median survival was 13.4 versus 11.4 months for sorafenib versus placebo ( HR = 1.01 ; 95 % CI : 0.71−1.44 ; P = 0.95 ) . Addition of sorafenib versus placebo  increased grade 3/4 h and –foot skin reaction ( 39 % vs. 5 % ) , stomatitis ( 10 % vs. 0 % ) , fatigue ( 18 % vs. 9 % ) , and dose reductions that were more frequent ( 51.9 % vs. 7.8 % ) . Conclusion : The addition of sorafenib to gemcitabine/capecitabine provided a clinical ly small but statistically significant PFS benefit in HER2-negative advanced breast cancer patients whose disease progressed during/after  bevacizumab . Combination treatment was associated with manageable toxicities but frequently required dose reductions . Clin Cancer Res ; 19(10 ) ; 2745–54 . © 2013 AACR 
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Additionally , sunitinib seemed to have no substantial efficacy for metastatic breast cancer .
Toxicities were more frequent in patients receiving MATKIs .
Conclusion Overall , regimens consisting of MATKIs seemed not to be superior to chemotherapy alone in terms of PFS and OS , although significant improvement in ORR was observed .
However , the addition of sorafenib significantly improved PFS .