摘要
This phase Ⅲ trial aimed to compare ARX788,a site-specific,construct-homogeneous antibody-drug conjugate,with lapatinib plus capecitabine in patients with human epidermal growth factor receptor 2(HER2)-positive advanced breast cancer(ABC)who had progressed on one line of trastuzumab based regimen.Eligible patients were randomized(1:1)to receive ARX788(1.5 mg/kg,IV,Q3W)or lapatinib plus capecitabine(LC:lapatinib 1250 mg QD;capecitabine 1000 mg/m^(2) BID,days 1-14,Q3W)and stratified by prior chemotherapy lines(0-1 versus>1)and visceral metastasis(yes versus no).The primary outcome was progression-free survival(PFS)assessed by a blinded independent central review(BICR).A total of 441 patients were randomly assigned to receive either ARX788(n=221)or LC(n=220).The median PFS was 11.3(95%confidence interval[CI],8.4-13.8)months with ARX788 compared with 8.2(95%CI,6.9-8.7)months with LC,as per BICR(hazard ratio[HR]0.64,p=0.0006).Frequencies of treatment-related adverse events(TRAEs)of any grade were 98.6%and 99.1%for ARX788 and LC,respectively.Grade≥3 TRAEs were 41.4%and 40.0%,respectively,the most common adverse events were blurred vision(12.3%),dry eye(9.1%),keratopathy(5.9%),and interstitial lung disease(ILD,5.9%)with ARX788;hand-foot syndrome(18.1%)and hypokalemia(5.1%)with LC;all the hematological and gastrointestinal events of grade≥3 with ARX788 were less than 3%.Six treatment-related deaths occurred,with three cases possibly related to ILD.ARX788 significantly improved PFS compared with LC in patients with HER2-positive ABC with a distinct toxicity profile,supporting it as a potential treatment option.
