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 ? "
Adjuvant lapatinib for women with early-stage HER2-positive breast cancer: a randomised, controlled, phase 3 trial.
BACKGROUND Worldwide , many patients with HER2-positive early stage breast cancer do not receive trastuzumab-the st and ard adjuvant treatment . We investigated the efficacy and safety of adjuvant lapatinib for patients with trastuzumab-naive HER2-positive early-stage breast cancer , started at any time after diagnosis . METHODS This study was a placebo-controlled , multicentre , r and omised phase 3 trial . Women out patients from 405 [ corrected ] centres in 33 countries [ corrected ] with HER2-positive early-breast cancer who had previously received adjuvant chemotherapy but not trastuzumab were r and omly assigned ( 1:1 ) to receive daily lapatinib ( 1500 mg ) or daily placebo for 12 months . R and omisation was done with a computer-generated sequence , stratified by time since diagnosis , lymph node involvement at diagnosis , and tumour hormone-receptor status . Investigators , site staff , and patients were masked to treatment assignment . The primary endpoint was disease-free survival in the intention-to-treat population . This study is registered with Clinical Trials.gov , number NCT00374322 . FINDINGS Between August , 2006 , and May , 2008 , 3161 women were enrolled and 3147 were assigned to lapatinib ( n=1571 ) or placebo ( n=1576 ) . After a median follow-up of 47·4 months ( range 0·4 - 60·0 ) in the lapatinib group and 48·3 ( 0·7 - 61·3 ) in the placebo group , 210 ( 13 % ) disease-free survival events had occurred in the lapatinib group versus 264 ( 17 % ) in the placebo group ( hazard ratio [ HR ] 0·83 , 95 % CI 0·70 - 1·00 ; p=0·053 ) . Central review of HER2 status showed that only 2490 ( 79 % ) of the r and omised women were HER2-positive . 157 ( 13 % ) of 1230 confirmed HER2-positive patients in the lapatinib group and in 208 ( 17 % ) of 1260 in the placebo group had a disease-free survival event ( HR 0·82 , 95 % 0·67 - 1·00 ; p=0·04 ) . Serious adverse events occurred in 99 ( 6 % ) of 1573 patients taking lapatinib and 77 ( 5 % ) of 1574 patients taking placebo , with higher incidences of grade 3 - 4 diarrhoea ( 97 [ 6 % ] vs nine [ < 1 % ] ) , rash ( 72 [ 5 % ] vs three [ < 1 % ] ) , and hepatobiliary disorders ( 36 [ 2 % ] vs one [ < 1 % ] ) . INTERPRETATION Our data show that there was no significant difference in disease-free survival between groups when analysed in the intention-to-treat population . However , exploratory analyses restricted to patients who had HER2-positive disease confirmed by central fluorescence in-situ hybridisation review suggested marginal benefit with lapatinib in terms of disease-free survival . Thus lapatinib might be an option for women with HER2-positive breast cancer who do not or can not receive adjuvant trastuzumab . FUNDING GlaxoSmithKline
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 ? "