MAESTRO: A randomized, double-blind phase III study of evofosfamide (Evo) in combination with gemcitabine (Gem) in previously untreated patients (pts) with metastatic or locally advanced unresectable pancreatic ductal adenocarcinoma (PDAC).

作者：Eric Van Cutsem, Heinz‐Josef Lenz, Junji Furuse, Josep M. Tabernero, Volker Heinemann, Tatsuya Ioka, Igor S. Bazin, Makoto Ueno, Tibor Csőszi, Harpreet Singh Wasan, Bohuslav Melichar, Petr Karásek, Teresa Mercade Macarulla, Carmen Guillén‐Ponce, Ewa Kalinka‐Warzocha, Zsolt Horváth, Hans Prenen, Michael Schlichting, Ayman B. Ibrahim, Johanna C. Bendell · 发表于：Journal of Clinical Oncology · 年份：2016 · DOI：10.1200/jco.2016.34.15_suppl.4007 · 被引用次数：76 · 研究领域：Cancer, Hypoxia, and Metabolism、Cancer Genomics and Diagnostics、Epigenetics and DNA Methylation

4007 Background: Hypoxia in PDAC is associated with disease progression and poor prognosis. Evo is a hypoxia-activated prodrug of Br-IPM that is preferentially activated under hypoxic conditions. The addition of Evo to Gem significantly improved PFS in a randomized phase II trial in advanced PDAC (NCT01144455). Methods: MAESTRO was an international, randomized, double-blind, placebo-controlled phase III trial of Evo/Gem vs Placebo (Pbo)/Gem in pts with locally advanced unresectable or metastatic PDAC (NCT01746979). Evo 340 mg/m2 or matched Pbo and Gem 1,000 mg/m2 were administered IV on days 1, 8, and 15 of a 28-day cycle. Key eligibility criteria included ECOG PS 0/1. The primary endpoint was overall survival (OS). 660 patients were to be randomized 1:1 to obtain 508 events (deaths) to assure 90% power to detect a hazard ratio (HR) of 0.75 for OS with a two-sided α of 0.05. Secondary endpoints included PFS and objective response rate (ORR). Results: From Jan 2013 to Nov 2014, 693 pts were randomized (346 Evo/Gem, 347 Pbo/Gem). Baseline characteristics were balanced. Median OS was 8.7 mo with Evo/Gem vs 7.6 mo with Pbo/Gem; HR = 0.84 (95% CI: 0.71–1.01, p = 0.059). Median PFS was 5.5 mo with Evo/Gem vs 3.7 mo with Pbo/Gem; HR = 0.77 (95% CI: 0.65–0.92, p = 0.004). Best ORR was 20% with Evo/Gem vs 16% with Pbo/Gem; odds ratio (OR) = 1.32 (95% CI: 0.88–1.97, p = 0.17). Confirmed ORR was 15% with Evo/Gem vs 9% with Pbo/Gem; OR = 1.90 (95% CI: 1.16 – 3.12, p = 0.009). Most common...