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

Primo N. Lara, Jean Yves Douillard, Kazuhiko Nakagawa, Joachim Von Pawel, Mark J. McKeage, Istvan Albert, Gyor̈gy Losonczy, Martin Reck, Dae Seog Heo, Xiaolin Fan, Abderrahim Fandi, Giorgio Scagliotti

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192 Citations (Scopus)

Abstract

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/m2) and carboplatin (area under the curve, 6.0) with or without ASA404 (1,800 mg m2), 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 survival (PFS). 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 inthe ASA404 arm. Conclusion: The addition of ASA404 to carboplatin and paclitaxel, although generally well tolerated, failed to improve frontline efficacy in advanced NSCLC.

Original languageEnglish
Pages (from-to)2965-2971
Number of pages7
JournalJournal of Clinical Oncology
Volume29
Issue number22
DOIs
Publication statusPublished - Aug 1 2011

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Lara, P. N., Douillard, J. Y., Nakagawa, K., Von Pawel, J., McKeage, M. J., Albert, I., Losonczy, G., Reck, M., Heo, D. S., Fan, X., Fandi, A., & Scagliotti, G. (2011). 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. Journal of Clinical Oncology, 29(22), 2965-2971. https://doi.org/10.1200/JCO.2011.35.0660