Longer trastuzumab duration ( hera : 2 years vs. 1 year ) showed no improvement in dfs or os and a higher rate of cardiac events .
In the neoadjuvant setting ( neoaltto , GeparQuinto , Neosphere ) , trastuzumab alone or in combination with another anti-her2 agent ( lapatinib , pertuzumab ) was compared with either lapatinib or pertuzumab alone and showed superior or equivalent rates of pathologic complete response .
In the adjuvant setting , lapatinib alone or in combination with trastuzumab , compared with trastuzumab alone ( altto ) or with placebo ( teach ) , was not superior in dfs .
BACKGROUND This systematic review addresses the question " What is the optimal targeted therapy for female patients with early-stage human epidermal growth factor receptor 2 (her2)-positive breast cancer ? "
6 months versus 12 months of adjuvant trastuzumab for patients with HER2-positive early breast cancer (PHARE): a randomised phase 3 trial.
BACKGROUND Since 2005 , 12 months of adjuvant trastuzumab has been the st and ard treatment for patients with HER2-positive early-stage breast cancer . However , the optimum duration of treatment has been debated . We did a non-inferiority trial of a shorter exposure of 6 months versus the st and ard 12 months of trastuzumab for patients with early breast cancer . METHODS We did an open-label , r and omised , phase 3 trial in 156 centres in France . Patients with HER2-positive early breast cancer who had received at least four cycles of chemotherapy , had breast-axillary surgery , and had received up to 6 months of trastuzumab ( administered by intravenous infusions over 30 - 90 min every 3 weeks ; initial loading dose 8 mg/kg ; 6 mg/kg thereafter ) before r and omisation were eligible . Patients were r and omly assigned via central r and omisation procedure with web-based software to continue trastuzumab for another 6 months ( 12 months total duration ; control group ) or to discontinue trastuzumab at 6 months ( 6 months total duration ; experimental group ) . R and omisation was stratified by concomitant or sequential administration of trastuzumab with chemotherapy , oestrogen-receptor status , and centre using a minimisation algorithm . The primary endpoint was disease-free survival , with a prespecified non-inferiority margin of 1·15 . Analyses were done in the intention-to-treat population . This study is registered at Clinical Trials.gov , number NCT00381901 . FINDINGS 1691 patients were r and omly assigned to receive 12 months of trastuzumab and 1693 to receive 6 months of trastuzumab ;  1690 patients in each group were included in the intention-to-treat analyses . After a median follow-up of 42·5 months ( IQR 30·1 - 51·6 ) , 175 disease-free survival events were noted in the 12-month group and 219 in the 6-month group . 2-year disease-free survival was 93·8 % ( 95 % CI 92·6 - 94·9 ) in the 12-month group and 91·1 % ( 89·7 - 92·4 ) in the 6-month group ( hazard ratio 1·28 , 95 % CI 1·05 - 1·56 ; p=0·29 ) . 119 ( 93 % ) of the 128 cardiac events ( clinical or based on assessment of left ventricular ejection fraction ) occurred while patients were receiving trastuzumab . Significantly more patients in the 12-month group experienced a cardiac event than did those in the 6-month group ( 96 [ 5·7 % ] of 1690 patients vs 32 [ 1·9 % ] of 1690 patients , p<0·0001 ) . INTERPRETATION After 3·5 years follow-up , we failed to show that 6 months of treatment with trastuzumab was non-inferior to 12 months of trastuzumab . Despite the higher rates of cardiac events , 12 months of adjuvant trastuzmab should remain the st and ard of care . FUNDING French National Cancer Institute
Longer trastuzumab duration ( hera : 2 years vs. 1 year ) showed no improvement in dfs or os and a higher rate of cardiac events .
In the neoadjuvant setting ( neoaltto , GeparQuinto , Neosphere ) , trastuzumab alone or in combination with another anti-her2 agent ( lapatinib , pertuzumab ) was compared with either lapatinib or pertuzumab alone and showed superior or equivalent rates of pathologic complete response .
In the adjuvant setting , lapatinib alone or in combination with trastuzumab , compared with trastuzumab alone ( altto ) or with placebo ( teach ) , was not superior in dfs .
BACKGROUND This systematic review addresses the question " What is the optimal targeted therapy for female patients with early-stage human epidermal growth factor receptor 2 (her2)-positive breast cancer ? "