Therapeutic vaccination with TG4010 and first-line chemotherapy in advanced non-small-cell lung cancer: a controlled phase 2B trial
| Autor: | 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 |
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| Přispěvatelé: | 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, International Drug Development Institute (IDDI) |
| Rok vydání: | 2011 |
| Předmět: |
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 |
| Zdroj: | Lancet Oncology Lancet Oncology, Elsevier, 2011, 12 (12), pp.1125-1133. 〈10.1016/S1470-2045(11)70259-5〉 Lancet Oncology, Elsevier, 2011, 12 (12), pp.1125-1133. ⟨10.1016/S1470-2045(11)70259-5⟩ |
| ISSN: | 1470-2045 |
| DOI: | 10.1016/s1470-2045(11)70259-5 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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