Randomized phase III placebo-controlled trial of carboplatin and paclitaxel with
or without the vascular disrupting agent vadimezan (ASA404) in advanced
non-small-cell lung cancer.
Author(s): Lara PN Jr, Douillard JY, Nakagawa K, von Pawel J, McKeage MJ, Albert I, Losonczy
G, Reck M, Heo DS, Fan X, Fandi A, Scagliotti G.
Affiliation(s): University of California, Davis Cancer Center, 4501 X St, Suite 3016, Sacramento,
CA, USA. email@example.com
Publication date & source: 2011, J Clin Oncol. , 29(22):2965-71
PURPOSE: This phase III trial was conducted to test whether the novel vascular
disrupting agent ASA404 (vadimezan), when combined with first-line platinum-based
chemotherapy, improves survival in patients with advanced non-small-cell lung
cancer (NSCLC) versus chemotherapy alone.
PATIENTS AND METHODS: Patients with advanced stage IIIB or IV NSCLC, stratified
by sex and tumor histology, were randomly assigned 1:1 to paclitaxel (200
mg/m(2)) and carboplatin (area under the curve, 6.0) with or without ASA404
(1,800 mg m(2)), given intravenously once every 3 weeks for six cycles followed
by maintenance ASA404 or placebo. Primary end point was overall survival (OS);
secondary end points included overall response rate (ORR) and progression-free
RESULTS: One thousand two hundred ninety-nine patients were randomly assigned.
The trial was stopped for futility at interim analysis. At final analysis, there
was no difference in OS seen between ASA404 (n = 649) and placebo (n = 650) arms:
median OS was 13.4 and 12.7 months respectively (hazard ratio [HR], 1.01; 95% CI,
0.85 to 1.19; P = .535). Similarly, no OS difference was seen in the histologic
(squamous or nonsquamous) and sex (male or female) strata. Median PFS was 5.5
months in both arms (HR, 1.04; P = .727), while ORR was 25% in both arms (P =
1.0). Overall rate of adverse events (AEs) was comparable between the ASA404 and
placebo arms. Grade 4 neutropenia (27% v 19%) and infusion site pain (10% v 0.5%)
were reported more frequently in the ASA404 arm.
CONCLUSION: The addition of ASA404 to carboplatin and paclitaxel, although
generally well tolerated, failed to improve frontline efficacy in advanced NSCLC.