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 ? "
A phase III trial of adjuvant neratinib (NER) after trastuzumab (TRAS) in women with early-stage HER2+ breast cancer (BC).
TPS137 Background : The human epidermal growth factor receptors ( HER1 - 4 ) are frequently overexpressed in human tumors . Increased HER receptor signaling is associated with increased resistance to st and ard therapies and poor prognosis . TRAS , an anti-HER2 monoclonal antibody , reduces recurrences and improves disease-free survival ( DFS ) in patients ( pts ) with HER2 + early BC . However , 15 % to 25 % of TRAS-treated pts still experience relapsed disease at 5 yrs . NER is a small molecule , irreversible tyrosine kinase inhibitor of HER2 as well as HER1 and HER4 . In a phase II study , orally administered NER 240 mg/d was well tolerated with significant antitumor activity in pts with HER2 + BC , with or without prior TRAS ( objective response rates of 24 % and 56 % ; median progression-free survival of 22 wks and 40 wks , respectively ) . The current study will evaluate the efficacy and safety of  NER in pts with early-stage HER2 + BC after adjuvant TRAS .  METHODS This double-blind , placebo-controlled , multicenter , phase III study will include approximately 3,300 women with early-stage HER2-overexpressing/amplified , node-positive BC ( or no pathologic complete response after neoadjuvant therapy ) at high risk for recurrence . Pts will be r and omized within 1 yr of prior adjuvant TRAS to oral NER 240 mg or placebo daily for 1 yr . Pts will be followed for up to 5 yrs post-r and omization for recurrence and /or survival . Primary endpoint is DFS ( time to disease recurrence or death ) , using a 1-sided log-rank test to compare treatment arms and a Cox proportional hazards regression model for hazard ratio estimation . Other efficacy endpoints include DFS including ductal carcinoma in situ , time to distant recurrence , distant DFS , incidence of central nervous system recurrence , and overall survival . Safety will be monitored , with particular attention to diarrhea . Biomarker analyses ( including HER2 confirmation from archived sample s ) and health-related quality of life ( FACT-B and EQ-5D ) will also be assessed . RESULTS As of Jan 25 , 2011 , a total of 2,050 pts have been r and omized , including 934 high-risk pts . CONCLUSIONS Recruitment is planned to continue until late 2013 . As of Nov 3 , 2010 , the IDMC recommended the trial to continue
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 ? "