1250P - Disrupt: a randomized phase 2 trial of ombrabulin (AVE8062) combined with a taxane-platinum regimen in the first-line treatment of metastatic non-sm...

Date 29 September 2012
Event ESMO Congress 2012
Session Poster presentation I
Topics Anti-Cancer Agents & Biologic Therapy
Non-Small-Cell Lung Cancer, Metastatic
Presenter Joachim von Pawel
Authors J. von Pawel1, V. Gorbounova2, M. Reck3, D. Kowalski4, A. Allard5, M. Chadjaa6, A. Rey6, J. Bennouna7, F. Grossi On Behalf Of The Disrupt Investigators8
  • 1Department Of Medicine Iii, Asklepios Fachkliniken, 81243 - Muenchen/DE
  • 2Oncology, Cancer Research Centre, Moscow/RU
  • 3Thoracic Oncology, Hospital Grosshansdorf, 22927 - Grosshansdorf/DE
  • 4Oncology, Maria Sklodowska-Curie Memorial Cancer Centre, Warsaw/PL
  • 5Bio Stats, Sanofi, Chilly-Mazarin/FR
  • 6Clinical, Sanofi, Vitry-sur-Seine/FR
  • 7Medical Oncology, Institut de Cancérologie de l’Ouest, Herblain/FR
  • 8Lung Cancer Unit, National Institute for Cancer Research, Genova/IT

Abstract

Introduction

Ombrabulin is a vascular disrupting agent and analogue of combretastatin A4 that damages established tumor vasculature, which causes tumor necrosis and regression. DISRUPT (NCT01263886) evaluated whether adding ombrabulin to a taxane-platinum doublet in the first-line setting improves outcomes in patients with metastatic NSCLC.

Methods

Patients (≥18 yrs of age, ECOG PS 0–1, stage IV) were randomized 1:1 to either ombrabulin 35 mg/m2 or placebo (Pbo) on day 1 followed by a taxane-platinum regimen on day 2 (docetaxel 75 mg/m2 + cisplatin 75 mg/m2 or paclitaxel 200 mg/m2 + carboplatin AUC 6), every 3 weeks. Randomization was stratified by histology (squamous/nonsquamous) and taxane-platinum regimen. Treatment was continued up to 6 cycles, or until unacceptable toxicity, disease progression, or consent withdrawal. The primary endpoint was progression-free survival (PFS) (stratified log-rank analysis; one-sided significance level 0.2). The study had 92% power to detect a 33% risk reduction in the hazard rate for progression (HR 0.67). Secondary endpoints included overall survival (OS), response rate (RR), and safety.

Results

From February 2011 to January 2012, a total of 176 patients were randomized (n = 88 in each group). Groups were balanced in terms of baseline characteristics. Overall, the median age was 62 yrs (range, 32 – 84), 76% were male, 66% were nonsquamous and 34% squamous, 52% received paclitaxel-carboplatin and 48% docetaxel-cisplatin. PFS was analyzed after 124 events (61 ombrabulin; 63 Pbo); median follow-up was 8 months. PFS was not significantly improved in the ombrabulin group versus Pbo (median 5.7 vs 5.5 months, respectively; HR 0.95; 60%CI 0.81–1.11; one-sided p = 0.39). Overall RR were similar (ombrabulin 32%; Pbo 31%). Median OS was 11.0 months in both arms. Safety profiles were comparable; rates of grade 3-4 adverse events were 57% for ombrabulin and 52% for Pbo.

Conclusions

This randomized phase 2 trial of ombrabulin combined with a platinum-taxane regimen did not meet the primary endpoint of improving PFS compared with Pbo in the first-line treatment of metastatic NSCLC. Study sponsored by Sanofi.

Disclosure

J. von Pawel: Member of Sanofi Steering Committee.

V. Gorbounova: Member of advisory board: Novartis and Pfizer Honoraria for lectures: Hoffman La Roche.

M. Reck: Ad board membership: Lilly, Hoffmann-La Roche, Daiichi-Sankyo, Pfizer, AstraZeneca, BMS Honoraria for lectures: Lilly, Hoffmann-La Roche, Daiichi-Sankyo, AstraZeneca.

A. Allard: Sanofi employee.

M. Chadjaa: Sanofi employee and stock holder.

A. Rey: Sanofi employee and stock held.

J. Bennouna: Advisory board: Sanofi-Aventis.

F. Grossi On Behalf of The Disrupt Investigators: Membership on advisory board: Sanofi.

All other authors have declared no conflicts of interest.