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

Research output: Contribution to journalArticle

191 Scopus citations

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 (US)
Pages (from-to)2965-2971
Number of pages7
JournalJournal of Clinical Oncology
Volume29
Issue number22
DOIs
StatePublished - Aug 1 2011

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Medicine(all)

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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