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Article Dans Une Revue Lancet Oncology Année : 2011

Therapeutic vaccination with TG4010 and first-line chemotherapy in advanced non-small-cell lung cancer: a controlled phase 2B trial.

Rodryg Ramlau
  • Fonction : Auteur
Zsolt Papai
  • Fonction : Auteur
Anne Madroszyk
  • Fonction : Auteur
Piotr Koralewski
  • Fonction : Auteur
Erich Stoelben
  • Fonction : Auteur
Denis Braun
  • Fonction : Auteur
Hervé Lena
  • Fonction : Auteur
Bruce Acres
  • Fonction : Auteur
Gisèle Lacoste
  • Fonction : Auteur
Bérangère Bastien
  • Fonction : Auteur
Annette Tavernaro
  • Fonction : Auteur
Nadine Bizouarne
  • Fonction : Auteur
Jean-Yves Bonnefoy
  • Fonction : Auteur
Jean-Marc Limacher
  • Fonction : Auteur

Résumé

BACKGROUND: Chemotherapy is the standard of care for advanced stages of non-small-cell lung cancer (NSCLC). TG4010 is a targeted immunotherapy based on a poxvirus (modified vaccinia virus Ankara) that codes for MUC1 tumour-associated antigen and interleukin 2. This study assessed TG4010 in combination with first-line chemotherapy in advanced NSCLC. METHODS: 148 patients with advanced (stage IIIB [wet] or IV) NSCLC expressing MUC1 by immunohistochemistry, and with performance status 0 or 1, were enrolled in parallel groups in this open-label, phase 2B study. 74 patients were allocated to the combination therapy group, and received TG4010 (10(8) plaque forming units) plus cisplatin (75 mg/m(2) on day 1) and gemcitabine (1250 mg/m(2) on days 1 and 8) repeated every 3 weeks for up to six cycles. 74 patients allocated to the control group received the same chemotherapy alone. Patients were allocated using a dynamic minimisation procedure stratified by centre, performance status, and disease stage. The primary endpoint was 6-month progression-free survival (PFS), with a target rate of 40% or higher in the experimental group. Analyses were done on an intention-to-treat basis. This study is completed and is registered with ClinicalTrials.gov, number NCT00415818. FINDINGS: 6-month PFS was 43*2% (32 of 74; 95% CI 33*4-53*5) in the TG4010 plus chemotherapy group, and 35*1% (26 of 74; 25*9-45*3) in the chemotherapy alone group. Fever, abdominal pain, and injection-site pain of any grade according to National Cancer Institute Common Toxicity Criteria were more common in the TG4010 group than in the chemotherapy alone group: 17 of 73 patients (23*3%) versus six of 72 (8*3%), 12 (16*4%) versus two (2*8%), and four (5*5%) versus zero (0%), respectively. The most common grade 3-4 adverse events were neutropenia (33 [45*2%] of patients in the TG4010 plus chemotherapy group vs 31 [43*1%] in the chemotherapy alone group) and fatigue (18 [24*7%] vs 13 [18*1%]); the only grade 3-4 events that differed significantly between groups were anorexia (three [4*1%] vs 10 [13*9%]) and pleural effusion (none vs four [5*6%]). 38 of 73 patients (52*1%) in the TG4010 plus chemotherapy group and 34 of 72 (47*2%) in the chemotherapy alone group had at least one serious adverse event. INTERPRETATION: This phase 2B study suggests that TG4010 enhances the effect of chemotherapy in advanced NSCLC. A confirmatory phase 2B-3 trial has been initiated. FUNDING: Transgene SA, Advanced Diagnostics for New Therapeutic Approaches (ADNA)/OSEO.

Domaines

Cancer

Dates et versions

hal-00718841 , version 1 (18-07-2012)

Identifiants

Citer

Elisabeth Quoix, Rodryg Ramlau, Virginie Westeel, Zsolt Papai, Anne Madroszyk, et al.. Therapeutic vaccination with TG4010 and first-line chemotherapy in advanced non-small-cell lung cancer: a controlled phase 2B trial.. Lancet Oncology, 2011, 12 (12), pp.1125-1133. ⟨10.1016/S1470-2045(11)70259-5⟩. ⟨hal-00718841⟩
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