Pneumologie 2013; 67 - P50
DOI: 10.1055/s-0033-1334708

DISRUPT: A randomized phase 2 trial of ombrabulin (AVE8062) combined with a taxane-platinum regimen in the first-line treatment of metastatic non-small cell lung cancer (NSCLC)

J von Pawel 1, V Gorbounova 2, M Reck 3, DM Kowalski 4, A Allard 5, M Chadjaa 6, A Rey 6, J Bennouna 7, F Grossi 8
  • 1Asklepiosfachkliniken München Gauting
  • 22cancer Research Center, Moskau, Russische Föderation
  • 3Department of Thoracic Oncology, Hospital Großhansdorf
  • 4Maria Sklodowska-Curie Memorial Cancer Centre, Warschau, Polen
  • 5Sanofi, Chilly-Mazarin, Frankreich
  • 6Sanofi, Vitry-Sur-Seine, Frankreich
  • 7Institut de Cancérologie de L'ouest, Nantes Saint Herblain, Frankreich
  • 8Istituto Nazionale Per la Ricerca Sul Cancro, Genua, Italien

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 1st-line setting improves outcomes in patients with metastatic NSCLC.

Methods: Patients (≥18yrs, ECOG 0 – 1, stage IV) were randomized 1:1 to ombrabulin 35 mg/m2 or placebo (Pbo) on D1 followed by a taxane-platinum regimen on D2 (docetaxel 75 mg/m2 + cisplatin 75 mg/m2 or paclitaxel 200 mg/m2 + carboplatin AUC 6), q3wk. Randomization was stratified by histology (squamous/nonsquamous) and taxane-platinum regimen. Treatment was continued to 6 cycles, or to unacceptable toxicity, disease progression, or consent withdrawal. 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 OS, response rate (RR), and safety.

Results: From Feb 2011 to Jan 2012, 176 patients were randomized (n = 88 each group). Baseline characteristics were balanced. Median age was 62yrs (range 32 – 84), 76% male, 66% 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 mos. PFS was not significantly improved in the ombrabulin group vs. Pbo (median 5.7 vs. 5.5 mos, respectively; HR 0.95; 60% CI 0.81 – 1.11; p = 0.39). Overall RR were similar (ombrabulin 32%; Pbo 31%). Median OS was 11.0 mos 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 plus a platinum-taxane regimen did not meet the primary endpoint of improving PFS compared with Pbo in the 1st-line treatment of metastatic NSCLC. Sponsored by Sanofi. Presented at ESMO 2012; Ann Oncol 23: Suppl Abs 1250P.