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 ? "
Treatment with trastuzumab for 1 year after adjuvant chemotherapy in patients with HER2-positive early breast cancer: a 4-year follow-up of a randomised controlled trial.
BACKGROUND Treatment with adjuvant trastuzumab for 1 year improves disease-free survival and overall survival in patients with human epidermal growth factor receptor 2 (HER2)-positive early breast cancer . We aim ed to assess disease-free survival and overall survival after a median follow-up of 4 years for patients enrolled on the Herceptin Adjuvant ( HERA ) trial . METHODS The HERA trial is an international , multicentre , r and omised , open-label , phase 3 trial comparing treatment with trastuzumab for 1 and 2 years with observation after st and ard neoadjuvant , adjuvant chemotherapy , or both in patients with HER2-positive early breast cancer . The primary endpoint was disease-free survival . After a positive first interim analysis at a median follow-up of 1 year for the comparison of treatment with trastuzumab for 1 year with observation , event-free patients in the observation group were allowed to cross over to receive trastuzumab . We report trial outcomes for the 1-year trastuzumab and observation groups at a median follow-up of 48·4 months ( IQR 42·0 - 56·5 ) and assess the effect of the extensive crossover to trastuzumab . Our analysis was by intention-to-treat . The HERA trial is registered with the European Clinical Trials Data base , number 2005 - 002385 - 11 . FINDINGS The HERA trial population comprised 1698 patients r and omly assigned to the observation group and 1703 to the 1-year trastuzumab group . Intention-to-treat analysis of disease-free survival showed a significant benefit in favour of patients in the 1-year trastuzumab group ( 4-year disease-free survival 78·6 % ) compared with the observation group ( 4-year disease-free survival 72·2 % ; hazard ratio [ HR ] 0·76 ; 95 % CI 0·66 - 0·87 ; p<0·0001 ) . Intention-to-treat analysis of overall survival showed no significant difference in the risk of death ( 4-year overall survival 89·3%vs 87·7 % , respectively ; HR 0·85 ; 95 % CI 0·70 - 1·04 ; p=0·11 ) . Overall , 885 patients ( 52 % ) of the 1698 patients in the observation group crossed over to receive trastuzumab , and began treatment at median 22·8 months ( range 4·5 - 52·7 ) from r and omisation . In a non-r and omised comparison , patients in the selective-crossover cohort had fewer disease-free survival events than patients remaining in the observation group ( adjusted HR 0·68 ; 95 % CI 0·51 - 0·90 ; p=0·0077 ) . Higher incidences of grade 3 - 4 and fatal adverse events were noted on 1-year trastuzumab than in the observation group . The most common grade 3 or 4 adverse events , each in less than 1 % of patients , were congestive cardiac failure , hypertension , arthralgia , back pain , central -line infection , hot flush , headache , and diarrhoea . INTERPRETATION Treatment with adjuvant trastuzumab for 1 year after chemotherapy is associated with significant clinical benefit at 4-year median follow-up . The substantial selective crossover of patients in the observation group to trastuzumab was associated with improved outcomes for this cohort . FUNDING F Hoffmann-La Roche , Michelangelo Foundation
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 ? "