 In the subsequent randomized international Phase 3 study MPACT, CA046, NCT00394251 that enrolled 861 patients with metastatic pancreatic cancer, nab-paclitaxel in combination with gemcitabine exhibited a clinically meaningful, statistically significant improvement in OS and progression-free survival PFS. The median OS primary endpoint in the intent-to-treat population was 8.5 months 95 CI 7.89-9.53 with nab-paclitaxelgemcitabine compared with 6.7 months 95 CI 6.01-7.23 with gemcitabine, p 0.0001, HR 0.72 95 CI 0.617-0.835. Long-term survival was improved in the nab-paclitaxelgemcitabine arm versus gemcitabine alone, with a 59 increase at 1 year 35 versus 22 and doubling at 2 years 9 versus 4. The secondary PFS, overall response rate ORR and all other efficacy endpoints showed consistent, statistically significant improvements with nab-paclitaxelgemcitabine, supporting the results from the primary analysis of OS. Specifically, PFS by independent review was 5.5 months 95 CI 4.47-5.95 versus 3.7 months 95 CI 3.61-4.04 in the nab-paclitaxelgemcitabine arm versus gemcitabine alone arms, respectively p 0.0001; HR 0 .69; 95 CI 0.581-0.821. The improvement in PFS corresponded to a 31 reduction in the risk of progression or death with nab-paclitaxelgemcitabine. Furthermore, in this study of metastatic unresectable adenocarcinoma of the pancreas, subjects in the combination arm were on therapy longer than those receiving single agent gemcitabine, indicating disease improvement and tolerable treatment. The suitability of the dosing regimen was confirmed by the observation that the majority of patients did not require a dose reduction, and that 71 of nab-paclitaxel doses were delivered at the starting dose of 125 mgm2. The safety profile for both regimens was consistent with previous reports. Serious life threatening toxicities were not increased; AEs were acceptable and manageable. The most notable differences in toxicity between the 2 treatment arms was peripheral neuropathy, which was cumulative and rapidly reversible with dose delay and reduction, and neutropenia, which was manageable with dose delays and dose reductions. The incremental risks of sepsis and pneumonitis were managed by protocol amendments to increase awareness, and for early diagnosis and treatment to reduce the risk of fatal outcomes. Since the above described initial analysis of the MPACT study, the updated OS with a cutoff of May 2013 showed that the benefit continued to improve with nab-paclitaxel in combination with gemcitabine, with 8.7 versus 6.6 median months, respectively. The updated survival rates also significantly favored nab-paclitaxel plus gemcitabine at year 1 35 versus 22, year 2 10 versus 5, and year 3 4 versus 0 as compared with gemcitabine alone. 