1. Therapeutic vaccination with TG4010 and first-line chemotherapy in advanced non-small-cell lung cancer: a controlled phase 2B trial
- Author
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Didier Debieuvre, Jean-Marc Limacher, Elisabeth Quoix, A. Madroszyk, Marc Buyse, Jean-Yves Bonnefoy, Z. Papai, Erich Stoelben, Gisèle Lacoste, Piotr Koralewski, Hervé Lena, Denis Braun, Alain Rivière, Marie-Pierre Chenard, Bérangère Bastien, Jean-Luc Breton, Annette Tavernaro, Rodryg Ramlau, Bruce Acres, Nadine Bizouarne, Virginie Westeel, Service de pneumologie, CHU Strasbourg-Hopital Civil, Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC ( CEF2P / CARCINO ), Université Bourgogne Franche-Comté ( UBFC ) -Université de Franche-Comté ( UFC ) -Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ), Laboratoire d'Ingénierie des Systèmes Mécaniques et des MAtériaux ( LISMMA ), Université Paris 8 Vincennes-Saint-Denis ( UP8 ) -SUPMECA - Institut supérieur de mécanique de Paris, Centre Hospitalier de Belfort-Montbéliard, Service de Pneumologie, CHI de la Haute-Saône, International Drug Development Institute ( IDDI ), Service d'Anatomie Pathologique Générale, CHU Strasbourg-Hôpital de Hautepierre [Strasbourg], Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC (EA 3181) (CEF2P / CARCINO), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Laboratoire d'Ingénierie des Systèmes Mécaniques et des MAtériaux (LISMMA), Université Paris 8 Vincennes-Saint-Denis (UP8)-SUPMECA - Institut supérieur de mécanique de Paris (SUPMECA), CH Belfort-Montbéliard, and International Drug Development Institute (IDDI)
- Subjects
Male ,Lung Neoplasms ,MESH: Chi-Square Distribution ,MESH : Antineoplastic Combined Chemotherapy Protocols ,medicine.medical_treatment ,MESH: Membrane Glycoproteins ,MESH : Aged ,MESH: Risk Assessment ,Deoxycytidine ,Gastroenterology ,MESH: Cancer Vaccines ,[ SDV.CAN ] Life Sciences [q-bio]/Cancer ,0302 clinical medicine ,Antineoplastic Combined Chemotherapy Protocols ,MESH: Vaccinia virus ,Clinical endpoint ,MESH : Neoplasm Staging ,MESH: Treatment Outcome ,Vaccines, Synthetic ,0303 health sciences ,Membrane Glycoproteins ,MESH: Middle Aged ,MESH : Vaccinia virus ,MESH : Antimetabolites, Antineoplastic ,MESH : Chemotherapy, Adjuvant ,3. Good health ,MESH: Antineoplastic Combined Chemotherapy Protocols ,Oncology ,030220 oncology & carcinogenesis ,Antimetabolites, Antineoplastic ,medicine.medical_specialty ,MESH: Vaccines, Synthetic ,Risk Assessment ,Disease-Free Survival ,MESH : Cisplatin ,03 medical and health sciences ,Humans ,MESH : Middle Aged ,MESH : Lung Neoplasms ,MESH : Vaccines, Synthetic ,Adverse effect ,MESH: Kaplan-Meier Estimate ,Aged ,Chi-Square Distribution ,MESH: Humans ,MESH : Carcinoma, Non-Small-Cell Lung ,MESH : Chi-Square Distribution ,MESH: Deoxycytidine ,MESH : Humans ,MESH: Adult ,MESH: Interleukin-2 ,MESH : Proportional Hazards Models ,medicine.disease ,MESH: Lung Neoplasms ,MESH: Disease-Free Survival ,Cisplatin ,MESH: Female ,MESH: Mucin-1 ,Time Factors ,MESH : Membrane Glycoproteins ,Kaplan-Meier Estimate ,MESH: Proportional Hazards Models ,Risk Factors ,MESH: Risk Factors ,Carcinoma, Non-Small-Cell Lung ,MESH : Female ,MESH : Risk Assessment ,MESH: Aged ,MESH: Antimetabolites, Antineoplastic ,MESH : Cancer Vaccines ,MESH: Neoplasm Staging ,Middle Aged ,MESH : Adult ,MESH : Risk Factors ,Europe ,Treatment Outcome ,Chemotherapy, Adjuvant ,MESH: Chemotherapy, Adjuvant ,MESH : Mucin-1 ,MESH : Disease-Free Survival ,Female ,MESH : Time Factors ,medicine.drug ,Adult ,Combination therapy ,MESH : Male ,MESH : Europe ,Vaccinia virus ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,MESH : Treatment Outcome ,Neutropenia ,Cancer Vaccines ,MESH : Interleukin-2 ,MESH : Kaplan-Meier Estimate ,MESH : Deoxycytidine ,Internal medicine ,medicine ,Lung cancer ,Neoplasm Staging ,Proportional Hazards Models ,030304 developmental biology ,Chemotherapy ,Performance status ,business.industry ,Mucin-1 ,MESH: Time Factors ,Gemcitabine ,MESH: Male ,Surgery ,MESH: Cisplatin ,Interleukin-2 ,MESH: Europe ,business ,MESH: Carcinoma, Non-Small-Cell Lung - Abstract
International audience; 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.
- Published
- 2011
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