Randomized phase III study of weekly nab-paclitaxel plus gemcitabine versus gemcitabine alone in patients with metastatic adenocarcinoma of the pancreas (MPACT).

Abstract

LBA148 Background: nab-Paclitaxel (nab-P, 130 nm albumin-bound paclitaxel) provides tumor selective localization via transcytosis across the endothelium, potential tumor uptake via macropinocytosis, and improved pharmacokinetics vs cremophor-paclitaxel. In vitro, nab-P increased tumoral gemcitabine (G) levels, and in a phase I/II study in metastatic pancreatic cancer (mPC) nab-P + G showed promising activity. Methods: Patients (pts) with mPC were randomized to nab-P 125 mg/m2, followed by G 1000 mg/m2 on days 1, 8, and 15 every 4 weeks or G 1000 mg/m2 weekly for 7 weeks (cycle 1), then on days 1, 8, and 15 every 4 weeks (≥ cycle 2). For the primary endpoint of overall survival (OS), 608 events from 842 patients provided a power of 0.9 to detect a HR of 0.769 (2-side α = 0.049). Results: 861 pts received therapy. Baseline pt characteristics were well balanced. Median age was 63 years, Karnofsky performance status was 90-100 in 60% and ≤80 in 40% of pts, 43% had head of pancreas lesions, 84% had liver and 39% had lung metastases, and 52% of pts had CA19-9 ≥59 x ULN. Treatment duration was 4 vs 3 months in nab-P + G vs G. The relative protocol G dose was 75% vs 85% in nab-P + G vs G; nab-P dose was 81%. OS, progression-free survival (PFS), time to treatment failure (TTF), and overall response rate (ORR) were significantly improved in the nab-P + G arm (Table). Most common grade ≥3 AEs were neutropenia (38% vs 27%), fatigue (17% vs 7%), and neuropathy (17% vs 1%) in the nab-P + G vs G arms. Grade ≥3 neuropathy improved to grade ≤1 in 29 days. Febrile neutropenia was reported in 3% (nab-P + G) vs 1% (G) pts. Conclusions: In this multinational, multiinstitutional study, nab-P + G was well tolerated and superior to G with statistically significant and clinically meaningful results in all endpoints and across subgroups. Clinical trial information: NCT00844649. [Table: see text]

Towards Optimal Design of Cancer Nanomedicines: Multi-stage Nanoparticles for the Treatment of Solid Tumors

“…6, the efficacy of the 20-nm multi-stage delivery system is not affected by a decrease in the size of the pores of the vessel wall and thus, it is expected that it will be effective even for tumors with poorly permeable vessels, such as pancreatic cancers. This finds clinical confirmation in the case of nab-paclitaxel (a 125-nm particle that reduces rapidly to 10 nm in size following disintegration in the blood), which can improve the overall survival of pancreatic adenocarcinoma patients 31 .…”

SPARC independent drug delivery and antitumour effects ofnab-paclitaxel in genetically engineered mice

“…Nanoparticle albumin-bound ( nab )-paclitaxel, an albumin-bound-stabilised paclitaxel formulation, has recently demonstrated significant improvements in median survival of patients with metastatic PDA when combined with gemcitabine 18. Since this drug combination represents the first therapeutic regimen that significantly extends survival of advanced stage PDA patients and is accompanied by an acceptable toxicity profile, nab -paclitaxel and gemcitabine will likely become the new standard of care chemotherapy and will shortly be implemented in national and international PDA treatment guidelines.…”

Prognostic and Predictive Blood-Based Biomarkers in Patients with Advanced Pancreatic Cancer: Results from CALGB80303 (Alliance)

“…Only recently has the survival for patients with metastatic pancreatic adenocarcinoma moved beyond 1 year (2), and the combination chemotherapy regimen responsible for this improvement, FOLFIRINOX, may not be appropriate for many patients with pancreatic cancer (3). Recently, the addition of Nab-paclitaxel to gemcitabine improved overall survival (OS) for patients with metastatic pancreatic cancer, however, this improvement was relatively modest (4). The clinical hallmarks of pancreatic cancer include marked cachexia, hypercoaguability, and pain syndromes out of proportion to the tumor volume (5).…”