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Background: nab-paclitaxel(nab-P; 130 nm albumin-bound paclitaxel)has demonstrated both single-agent activity and synergy with gemcitabine(G)in preclinical models of pancreatic cancer(PC).nab-P + G also demonstrated promising efficacy in a phase Ⅰ/Ⅱ study in metastatic PC(J ClinOncol.2011:4548-4554),warranting a phase Ⅲ study of nab-P + G vs G for metastatic PC.Methods: 861 patients(pts)with metastatic PC and a Karnofsky performance status(KPS)≥ 70 were randomized at 151 community and academic centers 1:1 to receive nab-P 125 mg/m2 + G 1000 mg/m2 days 1,8,and 15 every 4 weeks or G alone 1000 mg/m2weekly for 7 weeks followed by 1 week of rest(cycle 1)and then days 1,8,and 15 every 4 weeks(cycle ≥ 2).The primary endpoint was OS; secondary endpoints were PFS and ORR by independent review.Results: The median age was 63 years(range 27-88).KPS was 100(16%),90(44%),80(32%),and 70(7%).Pts had advanced disease with liver metastases(84%),≥ 3 metastatic sites(46%),and CA19-9 ≥ 59 × ULN(46%).Nab-P + G was superior to G for all efficacy endpoints: median OS was 8.5 vs.6.7 mo(HR 0.72; 95%CI,0.617-0.835; P = 0.000015); median PFS was 5.5 vs.3.7 mo(HR 0.69; 95%CI,0.581-0.821; P = 0.000024),and ORR was 23%vs.7%(P = 1.1 × 10-10)by RECIST v1.0.Metabolic response by PET in 257 patients was 63%for nab-P + G vs 38%for G(P = 0.000051).CA19-9 response(≥ 90%decrease)was 31%for nab-P + G vs.14%for G(P < 0.0001).Grade ≥ 3 Aes with nab-P + G vs.G included neutropenia(38%vs.27%),fatigue(17%vs.7%),diarrhea(6%vs 1%),and febrile neutropenia(3%vs.1%).Grade ≥ 3 peripheral neuropathy(PN)occurred in 17%vs.1%of pts who received nab-P + G vs.G,respectively; for nab-P + G,PN improved to grade ≤ 1 in a median 29 days,and 44%of patients resumed nab-P treatment.The median duration of treatment was 3.9 mo for nab-P + G and 2.8 mo for G.Conclusions: MPACT was a large,international study performed at community and academic centers.Nab-P + G was superior to G across all efficacy endpoints,had an acceptable toxicity profile,and is a new standard for the treatment of metastatic PC that could become the backbone for new regimens.