***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: The article presents final analyses of overall survival from a phase III trial of lapatinib and capecitabine in patients with human epidermal growth factor receptor 2–positive locally advanced or metastatic breast cancer that progressed following prior therapy including trastuzumab This phase II study ( VEG20007 ; NCT00347919 ) with r and omized and open-label components evaluated first-line lapatinib plus pazopanib therapy and /or lapatinib monotherapy in patients with human epidermal growth factor receptor type 2 (HER2)-positive advanced/metastatic breast cancer . Patients were enrolled sequentially into two cohorts : Cohort 1 , patients were r and omly assigned to lapatinib 1,000 mg plus pazopanib 400 mg or lapatinib 1,500 mg monotherapy ; Cohort 2 , patients received lapatinib 1,500 mg plus pazopanib 800 mg . The primary endpoint was week-12 progressive disease rate ( PDR ) for Cohort 1 . The principal secondary endpoint was week-12 response rate ( RR ) for Cohort 2 . Efficacy was assessed in patients with central ly confirmed HER2 positivity ( modified intent-to-treat population [ MITT ] ) . The study enrolled 190 patients ( Cohort 1 , combination n = 77 , lapatinib n = 73 ; Cohort 2 , n = 40 ) . The MITT population comprised n = 141 ( Cohort 1 ) and n = 36 ( Cohort 2 ) . In Cohort 1 , week-12 PDRs were 36.2 % ( combination ) versus 38.9 % ( lapatinib ; P = 0.37 for the difference ) . Week-12 RRs were 36.2 % ( combination ) versus 22.2 % ( lapatinib ) . In Cohort 2 , week-12 RR was 33.3 % . In Cohort 1 , grade 3/4 adverse events ( AEs ) included diarrhea ( combination , 9 % ; lapatinib , 5 % ) and hypertension ( combination , 5 % ; lapatinib , 0 % ) . Grade s 3/4 AEs in Cohort 2 included diarrhea ( 40 % ) , hypertension ( 5 % ) , and fatigue ( 5 % ) . Alanine aminotransferase elevations > 5 times the upper limit of normal occurred in Cohort 1 ( combination , 18 % ; lapatinib , 5 % ) and Cohort 2 ( 20 % ) . Upon conclusion , the combination of lapatinib plus pazopanib did not improve PDR compared with lapatinib monotherapy , although RR was increased . Toxicity was higher with the combination , including increased diarrhea and liver enzyme elevations Background A r and omized Phase II study evaluated the activity of weekly paclitaxel versus its combination with trastuzumab for treatment of patients with advanced breast cancer overexpressing HER-2 . Patients and methods Among 124 patients r and omized , 123 are assessable for toxicity and 118 for response . Patients received weekly paclitaxel single agent ( 80 mg/m2 ) or combined with trastuzumab ( 4 mg/kg loading dose , then weekly 2 mg/kg ) . HER-2 overexpression was determined by immunohistochemistry ( IHC ) . Patients with 2+/3 + IHC scores were eligible . IHC was compared with HER-2 serum extracellular domain ( ECD ) . Results Patient characteristics were similar in the two arms . Both treatments were feasible and well tolerated with no grade 4 hematologic toxicity . No patient developed cardiac toxicity . The combined treatment was statistically significant superior for overall response rate ( ORR ) ( 75 % vs. 56.9 % ; P = 0.037 ) , particularly in the subset of IHC 3 + patients ( 84.5 % vs. 47.5 % ; P = 0.00050 ) . A statistically significant better median time to progression was seen in the subgroup with IHC 3 + ( 369 vs. 272 days ; P = 0.030 ) and visceral disease ( 301 vs. 183 days ; P = 0.0080 ) treated with combination . Multivariable analysis of predictive factors showed that only IHC score retained statistically significant value for ORR ( P = 0.0035 ) . Conclusion Weekly paclitaxel plus trastuzumab is highly active and safe and it is superior to paclitaxel alone in patients with IHC score of 3 + BACKGROUND The safety and efficacy of neratinib monotherapy were compared with that of lapatinib plus capecitabine in patients with human epidermal growth factor receptor-2-positive ( HER2 + ) , locally advanced/metastatic breast cancer and prior trastuzumab treatment . METHODS Patients received neratinib 240 mg/d continuously ( n=117 ) or lapatinib 1250 mg/d continuously plus capecitabine 2000 mg/m(2 ) per day on days 1 - 14 of each 21-d cycle ( n=116 ) . The primary aim was to demonstrate non-inferiority of neratinib for progression-free survival ( PFS ) . FINDINGS The non-inferiority of neratinib was not demonstrated when compared with lapatinib plus capecitabine ( hazard ratio , 1.19 ; 95 % confidence interval , 0.89 - 1.60 ; non-inferiority margin , 1.15 ) . Median PFS for neratinib was 4.5 months versus 6.8 months for lapatinib plus capecitabine and median overall survival was 19.7 months versus 23.6 months . Objective response rate ( neratinib , 29 % versus lapatinib plus capecitabine , 41 % ; P=0.067 ) and clinical benefit rate ( 44 % versus 64 % ; P=0.003 ) were lower for the neratinib arm but consistent with previously reported results . In both treatment arms , diarrhoea was the most frequently reported treatment-related adverse event of any grade ( neratinib , 85 % versus lapatinib plus capecitabine , 68 % ; P=0.002 ) and of grade 3/4 ( 28 % versus 10 % ; P<0.001 ) , but was typically managed with concomitant anti-diarrhoeal medication and /or study treatment modification . Importantly , neratinib had no significant skin toxicity . INTERPRETATION The results are considered as inconclusive since neither inferiority nor non-inferiority of treatment with neratinib versus lapatinib plus capecitabine could be demonstrated . The study confirmed relevant single-agent clinical activity and acceptable overall tolerability of neratinib in patients with recurrent HER2 + advanced breast cancer Purpose Lapatinib is a small molecule , dual tyrosine kinase inhibitor of epidermal growth factor receptor ( EGFR ) and human epidermal growth factor receptor type 2 ( HER2 ) . Initial results of a phase III trial demonstrated that lapatinib plus capecitabine is superior to capecitabine alone in women with HER2-positive advanced breast cancer that progressed following prior therapy including trastuzumab . Up date d efficacy and initial biomarker results from this trial are reported . Methods Women with HER2-positive , locally advanced or metastatic breast cancer previously treated with anthracycline- , taxane- , and trastuzumab-containing regimens were r and omized to lapatinib 1,250 mg/day continuously plus capecitabine 2,000 mg/m2 days 1–14 of a 21-day cycle or capecitabine 2,500 mg/m2 on the same schedule . The primary endpoint was time to progression ( TTP ) as determined by an independent review panel . Relationship between progression-free survival ( PFS ) and tumor HER2 expression and serum levels of HER2 extracellular domain ( ECD ) were assessed . Results 399 women were r and omized . The addition of lapatinib prolonged TTP with a hazard ratio ( HR ) of 0.57 ( 95 % CI , 0.43–0.77 ; P < 0.001 ) and provided a trend toward improved overall survival ( HR : 0.78 , 95 % CI : 0.55–1.12 , P = 0.177 ) , and fewer cases with CNS involvement at first progression ( 4 vs. 13 , P = 0.045 ) . Baseline serum HER2 ECD did not predict for benefit from lapatinib . Conclusion The addition of lapatinib to capecitabine provides superior efficacy for women with HER2-positive , advanced breast cancer progressing after treatment with anthracycline- ,  taxane- , and trastuzumab-based therapy . Biomarker studies could not identify a subgroup of patients who failed to benefit from the addition of lapatinib to capecitabine BACKGROUND Continuation of trastuzumab plus capecitabine ( XH ) showed a significantly improved overall response rate and time to progression compared with capecitabine ( X ) alone in women with HER2-positive breast cancer progressing during trastuzumab treatment . Here , we report the final analysis on overall survival . PATIENTS AND METHODS Patients with HER2-positive , advanced breast cancer who progressed during treatment with trastuzumab with or without 1st-line metastatic chemotherapy  were prospect ively r and omised to X ( 2500mg/m(2 ) on days 1 - 14 , q3w ) or XH ( 6 (8)mg/kg , q3w ) . Overall survival was a pre-specified secondary end-point . RESULTS Median follow-up at June 2010 was 20.7months . Fifty nine of 74 and 60 of 77 patients died in the X and XH arm , respectively . Median overall survival was 20.6 and 24.9months with X and XH , respectively ( HR=0.94 [ 0.65 - 1.35 ] ; p=0.73 ) . Performance status and metastatic site were independent prognosticators for overall survival . No difference between treatment arms was observed for patients who achieved clinical response or clinical benefit , respectively . Patients who continued/restarted anti-HER2 treatment ( trastuzumab or lapatinib ) after 2nd progression ( N=52 ) had a post-progression survival of 18.8 compared with 13.3months for those who did not receive 3rd line treatment with anti-HER2 agents ( N=88 ) ( HR 0.63 ; p=0.02 ) . CONCLUSIONS Final overall survival analysis of the GBG-26 study did not demonstrate a significant survival benefit for treatment beyond progression with trastuzumab . However , in a post-hoc analysis , patients receiving anti-HER2 treatment as 3rd line therapy showed a better post-progression survival than those not receiving this targeted treatment BACKGROUND Lapatinib , a tyrosine kinase inhibitor of human epidermal growth factor receptor type 2 ( HER2 , also referred to as HER2/neu ) and epidermal growth factor receptor ( EGFR ) , is active in combination with capecitabine in women with HER2-positive metastatic breast cancer that has progressed after trastuzumab-based therapy . In this trial , we compared lapatinib plus capecitabine with capecitabine alone in such patients . METHODS Women with HER2-positive , locally advanced or metastatic breast cancer that had progressed after treatment with regimens that included an anthracycline , a taxane , and trastuzumab  were r and omly assigned to receive either combination therapy ( lapatinib at a dose of 1250 mg per day continuously plus capecitabine at a dose of 2000 mg per square meter of body-surface area on days 1 through 14 of a 21-day cycle ) or monotherapy ( capecitabine alone at a dose of 2500 mg per square meter on days 1 through 14 of a 21-day cycle ) . The primary end point was time to progression , based on an evaluation by independent review ers under blinded conditions . RESULTS The interim analysis of time to progression met specified criteria for early reporting on the basis of superiority in the combination-therapy group . The hazard ratio for the independently assessed time to progression was 0.49 ( 95 % confidence interval , 0.34 to 0.71 ; P<0.001 ) , with 49 events in the combination-therapy group and 72 events in the monotherapy group . The median time to progression was 8.4 months in the combination-therapy group as compared with 4.4 months in the monotherapy group . This improvement was achieved without an increase in serious toxic effects or symptomatic cardiac events . CONCLUSIONS Lapatinib plus capecitabine is superior to capecitabine alone in women with HER2-positive advanced breast cancer that has progressed after treatment with regimens that included an anthracycline , a taxane , and trastuzumab . ( Clinical Trials.gov number , NCT00078572 [ Clinical Trials.gov ] . ) BACKGROUND Trastuzumab emtansine ( T-DM1 ) is an antibody-drug conjugate incorporating the human epidermal growth factor receptor 2 (HER2)-targeted ant 
    Output:
    
RESULTS There is strong evidence that the addition of an anti-HER2 agent to st and ard chemo- or endocrine therapy  improves clinical ly relevant measurable outcomes .
There is also consistent evidence that initial treatment with trastuzumab alone ( and subsequent use of a cytotoxic ) is inferior to the initial combination of trastuzumab plus chemotherapy , and that either T-DM1 or dual anti-HER2 agents are superior to single anti-HER2 agent regimens .
There is no strong evidence that the use of more than one cytotoxic agent together with an anti-HER2 agent confers any benefit over a single cytotoxic , anti-HER2 combination .