- 作者：Charles Butts ; Mark A Socinski ; Paul L Mitchell ; Nick Thatcher ; Libor Havel ; Maciej Krzakowski ; Sergiusz Nawrocki ; Tudor-Eliade Ciuleanu ; Lionel Bosqu茅e ; Jos茅 Manuel Trigo ; Alex ; er Spira ; Lise Tremblay ; Jan Nyman ; Rodryg Ramlau ; Gun Wickart-Johansson ; Peter Ellis ; Oleg Gladkov ; Jos茅 Rodrigues Pereira ; Wilfried Ernst Erich Eberhardt ; Christoph Helwig ; Andreas Schr枚der ; et al.
- 刊名：Lancet Oncology
- 出版年：January, 2014
- 年：2014
- 卷：15
- 期：1
- 页码：59-68
- 全文大小：545 K
Summary
Background
Effective maintenance therapies after chemoradiotherapy for lung cancer are lacking. Our aim was to investigate whether the MUC1 antigen-specific cancer immunotherapy tecemotide improves survival in patients with stage III unresectable non-small-cell lung cancer when given as maintenance therapy after chemoradiation.Methods
The phase 3 START trial was an international, randomised, double-blind trial that recruited patients with unresectable stage III non-small-cell lung cancer who had completed chemoradiotherapy within the 4-12 week window before randomisation and received confirmation of stable disease or objective response. Patients were stratified by stage (IIIA vs IIIB), response to chemoradiotherapy (stable disease vs objective response), delivery of chemoradiotherapy (concurrent vs sequential), and region using block randomisation, and were randomly assigned (2:1, double-blind) by a central interactive voice randomisation system to either tecemotide or placebo. Injections of tecemotide (806 渭g lipopeptide) or placebo were given every week for 8 weeks, and then every 6 weeks until disease progression or withdrawal. Cyclophosphamide 300 mg/m2 (before tecemotide) or saline (before placebo) was given once before the first study drug administration. The primary endpoint was overall survival in a modified intention-to-treat population. This study is registered with , number .
Findings
From Feb 22, 2007, to Nov 15, 2011, 1513 patients were randomly assigned (1006 to tecemotide and 507 to placebo). 274 patients were excluded from the primary analysis population as a result of a clinical hold, resulting in analysis of 829 patients in the tecemotide group and 410 in the placebo group in the modified intention-to-treat population. Median overall survival was 25路6 months (95% CI 22路5-29路2) with tecemotide versus 22路3 months (19路6-25路5) with placebo (adjusted HR 0路88, 0路75-1路03; p=0路123). In the patients who received previous concurrent chemoradiotherapy, median overall survival for the 538 (65%) of 829 patients assigned to tecemotide was 30路8 months (95% CI 25路6-36路8) compared with 20路6 months (17路4-23路9) for the 268 (65%) of 410 patients assigned to placebo (adjusted HR 0路78, 0路64-0路95; p=0路016). In patients who received previous sequential chemoradiotherapy, overall survival did not differ between the 291 (35%) patients in the tecemotide group and the 142 (35%) patients in the placebo group (19路4 months [95% CI 17路6-23路1] vs 24路6 months [18路8-33路0], respectively; adjusted HR 1路12, 0路87-1路44; p=0路38). Grade 3-4 adverse events seen with a greater than 2% frequency with tecemotide were dyspnoea (49 [5%] of 1024 patients in the tecemotide group vs 21 [4%] of 477 patients in the placebo group), metastases to central nervous system (29 [3%] vs 6 [1%]), and pneumonia (23 [2%] vs 12 [3%]). Serious adverse events with a greater than 2% frequency with tecemotide were pneumonia (30 [3%] in the tecemotide group vs 14 [3%] in the placebo group), dyspnoea (29 [3%] vs 13 [3%]), and metastases to central nervous system (32 [3%] vs 9 [2%]). Serious immune-related adverse events did not differ between groups.
Interpretation
We found no significant difference in overall survival with the administration of tecemotide after chemoradiotherapy compared with placebo for all patients with unresectable stage III non-small-cell lung cancer. However, tecemotide might have a role for patients who initially receive concurrent chemoradiotherapy, and further study in this population is warranted.
Funding
Merck KGaA (Darmstadt, Germany).