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

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

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vadimezan
Carboplatin
Paclitaxel
Non-Small Cell Lung Carcinoma
Blood Vessels
Placebos
Survival
Disease-Free Survival
Medical Futility
Drug Therapy
Neutropenia
Platinum

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Medicine(all)

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

In: Journal of Clinical Oncology, Vol. 29, No. 22, 01.08.2011, p. 2965-2971.

Research output: Contribution to journalArticle

Lara, PN, Douillard, JY, Nakagawa, K, Von Pawel, J, McKeage, MJ, Albert, I, Losonczy, G, Reck, M, Heo, DS, 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, vol. 29, no. 22, pp. 2965-2971. https://doi.org/10.1200/JCO.2011.35.0660
Lara, Primo N ; Douillard, Jean Yves ; Nakagawa, Kazuhiko ; Von Pawel, Joachim ; McKeage, Mark J. ; Albert, Istvan ; Losonczy, Gyor̈gy ; Reck, Martin ; Heo, Dae Seog ; Fan, Xiaolin ; Fandi, Abderrahim ; Scagliotti, Giorgio. / 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. In: Journal of Clinical Oncology. 2011 ; Vol. 29, No. 22. pp. 2965-2971.
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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.",
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T1 - 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

AU - Lara, Primo N

AU - Douillard, Jean Yves

AU - Nakagawa, Kazuhiko

AU - Von Pawel, Joachim

AU - McKeage, Mark J.

AU - Albert, Istvan

AU - Losonczy, Gyor̈gy

AU - Reck, Martin

AU - Heo, Dae Seog

AU - Fan, Xiaolin

AU - Fandi, Abderrahim

AU - Scagliotti, Giorgio

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N2 - 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.

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