25605838
OBJECTIVE	CEREBEL compared the incidence of CNS metastases as first site of relapse in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer receiving lapatinib-capecitabine or trastuzumab-capecitabine .
METHODS	Patients without baseline CNS metastases were randomly assigned ( 1:1 ) to receive lapatinib-capecitabine ( lapatinib 1,250 mg per day ; capecitabine 2,000 mg/m ( 2 ) per day on days 1 to 14 every 21 days ) or trastuzumab-capecitabine ( trastuzumab loading dose of 8 mg/kg followed by an infusion of 6 mg/kg every 3 weeks ; capecitabine 2,500 mg/m ( 2 ) per day on days 1 to 14 every 21 days ) .
METHODS	The primary end point was incidence of CNS metastases as first site of relapse .
METHODS	Secondary end points included progression-free survival ( PFS ) and overall survival ( OS ) .
RESULTS	The study was terminated early with 540 enrolled patients ( 271 received lapatinib-capecitabine , and 269 received trastuzumab-capecitabine ) .
RESULTS	Incidence of CNS metastases as first site of relapse was 3 % ( eight of 251 patients ) for lapatinib-capecitabine and 5 % ( 12 of 250 patients ) for trastuzumab-capecitabine ( treatment differences , -1.6 % ; 95 % CI , -2 % to 5 % ; P = .360 ) .
RESULTS	PFS and OS were longer with trastuzumab-capecitabine versus lapatinib-capecitabine ( hazard ratio [ HR ] for PFS , 1.30 ; 95 % CI , 1.04 to 1.64 ; HR for OS , 1.34 ; 95 % CI , 0.95 to 1.64 ) .
RESULTS	Serious adverse events were reported in 13 % ( 34 of 269 patients ) and 17 % ( 45 of 267 patients ) of patients in the lapatinib-capecitabine and trastuzumab-capecitabine arms , respectively .
CONCLUSIONS	CEREBEL is inconclusive for the primary end point , and no difference was detected between lapatinb-capecitabine and trastuzumab-capecitabine for the incidence of CNS metastases .
CONCLUSIONS	A better outcome was observed with trastuzumab-capecitabine in the overall population .
CONCLUSIONS	However , lapatinib-capecitabine efficacy may have been affected by previous exposure to a trastuzumab regimen and/or when treatment was given as first - or second-line therapy in the metastatic setting .

