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

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• 作者：Prof Elisabeth Quoix ; MD^a ; ^{elisabeth.quoix@chru-strasbourg.fr} ; Prof Rodryg Ramlau ; MD^b ; Prof Virginie Westeel ; MD^c ; Zsolt Papai ; MD^d ; Anne Madroszyk ; MD^e ; Alain Riviere ; MD^f ; Piotr Koralewski ; MD^g ; Jean-Luc Breton ; MD^h ; Erich Stoelben ; MDⁱ ; Denis Braun ; MD^j ; Didier Debieuvre ; MD^k ; Hervé ; Lena ; MD^l ; Marc Buyse ; ScD^m ; Prof Marie-Pierre Chenard ; MDⁿ ; Bruce Acres ; PhD^o ; Gisè ; le Lacoste ; MD^o ; Bé ; rangè ; re Bastien ; MSc^o ; Annette Tavernaro ; MSc^o ; Nadine Bizouarne ; PhD^o ; Jean-Yves Bonnefoy ; PhD^o ; Jean-Marc Limacher ; MD^o
• 刊名：Lancet Oncology
• 出版年：2011
• 出版时间：November, 2011
• 年：2011
• 卷：12
• 期：12
• 页码：1125-1133
• 全文大小：1K

文摘

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Summary

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 (10⁸ plaque forming units) plus cisplatin (75 mg/m² on day 1) and gemcitabine (1250 mg/m² 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 , number .

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.