***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: 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 PURPOSE This r and omized , open-label phase II study compared the efficacy of sunitinib monotherapy with that of single-agent st and ard-of-care ( SOC ) chemotherapy in patients with previously treated advanced triple-negative breast cancer ( TNBC ) . METHODS Patients with advanced TNBC , relapsed after anthracycline- and taxane-based chemotherapy  , were r and omized to receive either sunitinib ( 37.5 mg/day ) or the investigator 's choice of SOC therapy .  Progression-free survival was the primary endpoint . RESULTS Median progression-free survival was 2.0 months with sunitinib and 2.7 months with SOC chemotherapy ( one-sided P = 0.888 ) . Median overall survival was not prolonged with sunitinib ( 9.4 months ) compared with SOC chemotherapy ( 10.5 months ; one-sided P = 0.839 ) . The objective response rate was 3 % with sunitinib and 7 % with SOC chemotherapy ( one-sided P = 0.962 ) . CONCLUSIONS Sunitinib monotherapy did not improve efficacy compared with SOC chemotherapy in patients with previously treated advanced TNBC , for which identification of effective treatments and therapeutic targets remains an urgent need . TRIAL REGISTRATION NCT00246571 PURPOSE This phase II study evaluated the efficacy and safety of ixabepilone as neoadjuvant therapy for invasive breast cancer not amenable to breast conservation surgery . Gene expression studies were undertaken using genes that were identified as potentially associated with sensitivity/resistance to ixabepilone in prior pre clinical investigations . PATIENTS AND METHODS Patients with invasive breast cancer > or= 3 cm were eligible .  Ixabepilone 40 mg/m(2 ) was administered as a 3-hour intravenous infusion on day 1 of a 21-day cycle for four or fewer cycles . RESULTS One hundred sixty-one patients were treated . The overall complete pathologic response ( pCR ) rate was 18 % in breast and 29 % in estrogen receptor ( ER ) -negative patients . Gene expression data were available for 134 patients .  ER gene expression ( ER1 ) was inversely related to pCR in breast and had a positive predictive value ( PPV ) of 37 % and negative predictive value ( NPV ) of 92 % . A 10-gene penalized logistic regression ( PLR ) model developed from 200 genes predictive of ixabepilone sensitivity in pre clinical experiments included ER and tau and had higher PPV ( 45 % ) and comparable NPV ( 89 % ) to ER1 . Grade 3 to 4 adverse events ( AEs ) were reported for 32 % of patients . Except for neutropenia and leukopenia , all grade 3 to 4 AEs occurred in < or= 3 % of patients . Reversible peripheral neuropathy was experienced by 3 % of patients . CONCLUSION ER , microtubule-associated protein tau , and a 10-gene PLR model that included ER were identified as predictors of ixabepilone-induced pCR . RESULTS indicate an inverse relation between ER expression levels and ixabepilone sensitivity . Neoadjuvant ixabepilone demonstrated promising activity and a manageable safety profile in patients with invasive breast tumors Gefitinib , an epidermal growth factor receptor tyrosine kinase inhibitor , has shown both anti-proliferative and anti-tumoral activity in breast cancer . This study was design ed to determine the effect of adding gefitinib to neoadjuvant epirubicin and cyclophosphamide ( EC ) on tumor response rates . Women with unilateral , primary operable , estrogen receptor negative invasive breast cancer ≥ 2 cm were eligible for inclusion . R and omized patients were to receive four cycles of neoadjuvant EC plus 12 weeks of either gefitinib ( 250 mg daily ) or placebo . Primary endpoint was pathologic complete response ( pCR ) , and secondary endpoints were complete response ( CR ) and overall objective response ( OR ) . 181 patients were r and omized .  A pCR was observed in 17 % ( 12/71 ) of patients treated with gefitinib and in 12 % ( 9/73 ) of patients treated with placebo ( 4.57 % difference , 95 % CI −7.19 to 6.33 ; P = 0.44 ) . CR was observed in 10 % of patients in both the gefitinib ( 7/71 ) and the placebo group ( 7/73 ) ( 0.27 % difference , 95 % CI −9.6 to 10.2 ; P = 0.96 ) . There was no significant difference in OR ( 5.96 % ; 95 % CI −9.9 to 21.9 ; P = 0.45 ) between the two groups . Post hoc subgroup analysis showed a significant difference in pCR between triple negative breast cancer ( TNBC ) and non-TNBC tumors ( P = 0.03 ) . More patients in the gefitinib arm had hematological toxicity ( P = 0.15 ) and discontinued treatment ( 9/94 vs. 2/86 ) because of adverse events ( AE ) . Tumor response rates were similar in the two groups . A significantly higher pCR rate was observed post hoc in TNBC versus non-TNBC independent of treatment . More patients in the gefitinib group discontinued treatment because of AE BACKGROUND We conducted a phase 3 , r and omized , double-blind , placebo-controlled trial of sorafenib , a multikinase inhibitor of tumor-cell proliferation and angiogenesis , in patients with advanced clear-cell renal-cell carcinoma . METHODS From November 2003 to March 2005 , we r and omly assigned 903 patients with renal-cell carcinoma that was resistant to st and ard therapy to receive either continuous treatment with oral sorafenib ( at a dose of 400 mg twice daily ) or placebo ;  451 patients received sorafenib and 452 received placebo .  The primary end point was overall survival . A single planned analysis of progression-free survival in January 2005 showed a statistically significant benefit of sorafenib over placebo . Consequently , crossover was permitted from placebo to sorafenib , beginning in May 2005 . RESULTS At the January 2005 cutoff , the median progression-free survival was 5.5 months in the sorafenib group and 2.8 months in the placebo group ( hazard ratio for disease progression in the sorafenib group , 0.44 ; 95 % confidence interval [ CI ] , 0.35 to 0.55 ; P<0.01 ) . The first interim analysis of overall survival in May 2005 showed that sorafenib reduced the risk of death , as compared with placebo ( hazard ratio , 0.72 ; 95 % CI , 0.54 to 0.94 ; P=0.02 ) , although this benefit was not statistically significant according to the O'Brien-Fleming threshold . Partial responses were reported as the best response in 10 % of patients receiving sorafenib and in 2 % of those receiving placebo ( P<0.001 ) . Diarrhea , rash , fatigue , and h and -foot skin reactions were the most common adverse events associated with sorafenib . Hypertension and cardiac ischemia were rare serious adverse events that were more common in patients receiving sorafenib than in those receiving placebo . CONCLUSIONS As compared with placebo , treatment with sorafenib prolongs progression-free survival in patients with advanced clear-cell renal-cell carcinoma in whom previous therapy has failed ; however , treatment is associated with increased toxic effects . ( Clinical Trials.gov number , NCT00073307 [ Clinical Trials.gov ] . ) BACKGROUND Whether progression-free survival ( PFS ) or overall survival ( OS ) is the more appropriate endpoint in clinical trials of metastatic cancer is controversial . In some disease and treatment setting s , an improvement in PFS does not result in an improved OS . METHODS We partitioned OS into two parts and expressed it as the sum of PFS and survival postprogression ( SPP ) . We simulated r and omized clinical trials with two arms that had respective medians for PFS of 6 and 9 months . We assumed no treatment difference in median SPP . We found the probability of a statistically significant benefit in OS for various median SPP and observed P values for PFS . We compared the sample sizes required for PFS vs OS for various median SPP . We compare our results with the literature regarding surrogacy of PFS for OS by use of the correlation between hazard ratios for PFS and OS . All statistical tests were two-sided . RESULTS For a trial with observed P value for improvement in PFS of .001 , there was a greater than 90 % probability for statistical significance in OS if median SPP was 2 months but less than 20 % if median SPP was 24 months . For a trial requiring 280 patients to detect a 3-month difference in PFS  , 350 and 2440 patients , respectively , were required to have the same power for detecting a real difference in OS that is carried over from the 3-month benefit in PFS when the median SPP was 2 and 24 months . CONCLUSIONS Addressing SPP is important in underst and ing treatment effects . For clinical trials with a PFS benefit , lack of statistical significance in OS does not imply lack of improvement in OS , especially for diseases with long median SPP . Although there may be no treatment effect on SPP , its variability so dilutes the OS comparison that statistical significance is likely lost . OS is a reasonable primary endpoint when median SPP is short but is too high a bar when median SPP is long , such as longer than 12 months In February 2008 , the U.S. Food and Drug Administration ( FDA ) granted accelerated approval to bevacizumab ( Avastin ) in combination with paclitaxel as first-line treatment for HER-2 negative metastatic breast cancer . Approval was based on the results of E2100 , a cooperative-group r and omized trial that showed a 5.5-month increase in progression-free survival associated with the addition of bevacizumab to paclitaxel therapy.1,2 Confirmatory studies by Genentech , the manufacturer , however , showed that bevacizumab 's benefits for progression-free survival may be appreciably smaller than those shown in E2100 and have demonstrated convincingly that the addition of bevacizumab to the chemotherapy agents they have tested offers no . . 
    Output:
    
No effect on OS was observed .
No PFS and OS benefit was detected with the other agents .
No improvement of OS was detected in patients treated with biological agents plus chemotherapy , while a significant PFS improvement was observed only for bevacizumab and cetuximab .