SAKK 17/04
Neoadjuvant chemotherapy and extrapleural pneumonectomy of malignant pleural mesothelioma with or without hemithoracic radiotherapy (SAKK 17/04): a randomised, international, multicentre phase 2 trial
Phase 2N = 151NCT00334594
- Population
- Adults aged 18-70 with pathologically confirmed resectable malignant pleural mesothelioma (T1-3 N0-2 M0), WHO performance status 0-1; part 2 only those with complete macroscopic resection
- Design
- Two-part phase 2 trial at 14 hospitals in Switzerland, Belgium and Germany (NCT00334594; the registry lists 153 actual enrolment, the paper analysed 151). Part 1 (single arm): three cycles of neoadjuvant cisplatin 75 mg/m2 and pemetrexed 500 mg/m2 every 3 weeks, then extrapleural pneumonectomy; 151 patients analysed, 113 (75%) had extrapleural pneumonectomy; primary endpoint the proportion with complete macroscopic resection (R0-1). Part 2: patients with complete macroscopic resection were randomised 1:1 (stratified by centre, histology, mediastinal node involvement and T stage) to high-dose hemithoracic radiotherapy or none; 54 patients, 27 per group; primary endpoint locoregional relapse-free survival, analysed by intention to treat. Enrolment 7 December 2005 to 17 October 2012; median follow-up 54.2 months (IQR 32-66). The abstract gives no hazard ratio or p value for part 2.
- Primary endpoint
- Complete macroscopic resection rate, Locoregional relapse-free survival
- Arms
- Part 1: neoadjuvant chemotherapy then EPP (experimental, n = 151): Three cycles of cisplatin 75 mg/m2 and pemetrexed 500 mg/m2 on day 1 every 3 weeks, then extrapleural pneumonectomy
- Part 2: no radiotherapy (control, n = 27): No hemithoracic radiotherapy after complete macroscopic resection
- Part 2: high-dose hemithoracic radiotherapy (experimental, n = 27): High-dose hemithoracic radiotherapy (target: entire hemithorax and thoracotomy channel, mediastinal nodal stations if affected or violated; boost to high-risk areas); median total dose 55.9 Gy (IQR 46.8-56.0)
- People
- Stahel RA, senior author Weder W, SAKK
Δ median Locoregional relapse-free survival+1.8 months
Show the numbers
| Endpoint | Analysis | Part 1: neoadjuvant chemotherapy then EPP / Part 2: high-dose hemithoracic radiotherapy | Part 2: no radiotherapy | Effect |
|---|---|---|---|---|
| Complete macroscopic resection rate151 patients analysed after neoadjuvant chemotherapy (part 1) | primarymedian follow-up 54.2 monthsStahel 2015 | 64% | — | 96 of 151 patients; 113 (75%) of the 151 had extrapleural pneumonectomy. Single-arm part, no comparison. The median follow-up applies to the whole analysis. |
| Locoregional relapse-free survivalPart 2 randomised patients (54), intention to treat | primaryStahel 2015 | median 9.4 months (6.5–11.9) | median 7.6 months (4.5–10.7) | Median locoregional relapse-free survival measured from surgery. The abstract prints no hazard ratio or p value for this comparison. |
| Endpoint | Analysis | Part 1: neoadjuvant chemotherapy then EPP / Part 2: high-dose hemithoracic radiotherapy | Part 2: no radiotherapy | Effect |
|---|---|---|---|---|
| Complete macroscopic resection rate151 patients analysed after neoadjuvant chemotherapy (part 1) | primarymedian follow-up 54.2 monthsStahel 2015 | 64% | — | 96 of 151 patients; 113 (75%) of the 151 had extrapleural pneumonectomy. Single-arm part, no comparison. The median follow-up applies to the whole analysis. |
| Locoregional relapse-free survivalPart 2 randomised patients (54), intention to treat | primaryStahel 2015 | median 9.4 months (6.5–11.9) | median 7.6 months (4.5–10.7) | Median locoregional relapse-free survival measured from surgery. The abstract prints no hazard ratio or p value for this comparison. |
- Part 2: no radiotherapy (control)
- Part 2: high-dose hemithoracic radiotherapy (experimental)
Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.
Data table (modelled values)
| Months | Part 2: no radiotherapy | Part 2: high-dose hemithoracic radiotherapy |
|---|---|---|
| 0 | 100.0% | 100.0% |
| 6 | 57.9% | 64.2% |
| 12 | 33.5% | 41.3% |
| 18 | 19.4% | 26.5% |
| 24 | 11.2% | 17.0% |
Appears in
Sources
Stahel RA, Riesterer O, Xyrafas A, Opitz I, Beyeler M, Ochsenbein A, et al. Neoadjuvant chemotherapy and extrapleural pneumonectomy of malignant pleural mesothelioma with or without hemithoracic radiotherapy (SAKK 17/04): a randomised, international, multicentre phase 2 trial. Lancet Oncol. 2015;16(16):1651-8.