Results of a randomized phase III trial (MPACT) of weekly <i>nab</i>-paclitaxel plus gemcitabine versus gemcitabine alone for patients with metastatic adenocarcinoma of the pancreas with PET and CA19-9 correlates.

4005^ 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 Clin Oncol. 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. Clinical trial information: NCT00844649.

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