GETUG 13
Personalised chemotherapy based on tumour marker decline in poor prognosis germ-cell tumours (GETUG 13): a phase 3, multicentre, randomised trial
Phase 3N = 263NCT00104676
- Population
- Patients over 16 years with non-seminomatous germ cell tumours meeting IGCCCG poor-prognosis criteria; 254 had a tumour marker assessment (51 favourable, 203 unfavourable decline)
- Design
- Phase 3 multicentre trial, 22 centres in France, the USA and Slovakia. All patients received one cycle of BEP; tumour markers were measured at day 18 to 21. Patients with a favourable marker decline continued BEP (non-randomised group); patients with an unfavourable decline were randomised 1:1 to BEP or a dose-dense regimen (paclitaxel-BEP plus oxaliplatin, then cisplatin, ifosfamide and bleomycin, with lenograstim support). Randomised comparison analysed in the intention-to-treat population.
- Primary endpoint
- PFS
- Arms
- Unfavourable decline, BEP (control, n = 98): Three further cycles of BEP (cisplatin 20 mg per square metre and etoposide 100 mg per square metre on 5 days, bleomycin 30 mg on days 1, 8 and 15) after the first cycle
- Unfavourable decline, dose-dense (experimental, n = 105): After one cycle of BEP: two cycles of paclitaxel before BEP plus oxaliplatin, followed by two cycles of cisplatin, ifosfamide and bleomycin, with lenograstim
- Favourable decline, BEP (not randomised) (control, n = 51): Three further cycles of BEP after the first cycle (reference group, not randomised)
- People
- Fizazi K, senior author Culine S
PFSHR 0.66 (95% CI 0.44–1.00)Δ 36-month PFS+11 pointsPFSHR 0.66 (95% CI 0.49–0.88)PFSHR 0.65 (95% CI 0.44–0.97)Δ 60-month PFS+12.2 pointsOSHR 0.74 (95% CI 0.46–1.20)
Show the numbers
| Endpoint | Analysis | Unfavourable decline, dose-dense | Unfavourable decline, BEP / Favourable decline, BEP (not randomised) | Effect |
|---|---|---|---|---|
| PFSITT population of the randomised comparison (203 patients with unfavourable marker decline) | primaryFizazi 2014 | 59% at 3 y (49–68%) | 48% at 3 y (38–59%) | HR 0.66 (95% CI 0.44–1.00)P=0.05Grade 3-4 neurotoxic events 7% versus 1% (dose-dense versus BEP). Salvage high-dose chemotherapy with stem-cell transplant was needed in 6% versus 16%. The upper confidence limit of the hazard ratio is 1.00 as printed, with p=0.05. |
| PFSFavourable decline (not randomised) versus unfavourable decline given BEP | exploratoryFizazi 2014 | — | 70% at 3 y (57–81%) | HR 0.66 (95% CI 0.49–0.88)P=0.01Non-randomised comparison of marker-decline groups, not a treatment effect. |
| PFSRandomised patients with unfavourable marker decline (203) | long term-updatemedian follow-up 7.1 yearsFizazi 2024 | 58.9% at 5 y | 46.7% at 5 y | HR 0.65 (95% CI 0.44–0.97)P=0.036JCO Clinical Trial Update. Salvage high-dose chemotherapy plus stem-cell transplant used in 8% versus 17% (P = .035). Only three patients in the dose-dense arm reported grade 3 motor neurotoxicity at 1 year. |
| OSRandomised patients with unfavourable marker decline (203) | long term-updatemedian follow-up 7.1 yearsFizazi 2024 | 70.9% at 5 y | 61.3% at 5 y | HR 0.74 (95% CI 0.46–1.20)P=0.22Not statistically significant; the update describes the survival difference as numerical. |
| Endpoint | Analysis | Unfavourable decline, dose-dense | Unfavourable decline, BEP / Favourable decline, BEP (not randomised) | Effect |
|---|---|---|---|---|
| PFSITT population of the randomised comparison (203 patients with unfavourable marker decline) | primaryFizazi 2014 | 59% at 3 y (49–68%) | 48% at 3 y (38–59%) | HR 0.66 (95% CI 0.44–1.00)P=0.05Grade 3-4 neurotoxic events 7% versus 1% (dose-dense versus BEP). Salvage high-dose chemotherapy with stem-cell transplant was needed in 6% versus 16%. The upper confidence limit of the hazard ratio is 1.00 as printed, with p=0.05. |
| PFSFavourable decline (not randomised) versus unfavourable decline given BEP | exploratoryFizazi 2014 | — | 70% at 3 y (57–81%) | HR 0.66 (95% CI 0.49–0.88)P=0.01Non-randomised comparison of marker-decline groups, not a treatment effect. |
| PFSRandomised patients with unfavourable marker decline (203) | long term-updatemedian follow-up 7.1 yearsFizazi 2024 | 58.9% at 5 y | 46.7% at 5 y | HR 0.65 (95% CI 0.44–0.97)P=0.036JCO Clinical Trial Update. Salvage high-dose chemotherapy plus stem-cell transplant used in 8% versus 17% (P = .035). Only three patients in the dose-dense arm reported grade 3 motor neurotoxicity at 1 year. |
| OSRandomised patients with unfavourable marker decline (203) | long term-updatemedian follow-up 7.1 yearsFizazi 2024 | 70.9% at 5 y | 61.3% at 5 y | HR 0.74 (95% CI 0.46–1.20)P=0.22Not statistically significant; the update describes the survival difference as numerical. |
Data table
| Endpoint | HR | 95% CI |
|---|---|---|
| PFS | 0.66 | 0.44–1 |
| PFS | 0.66 | 0.49–0.88 |
| PFS | 0.65 | 0.44–0.97 |
| OS | 0.74 | 0.46–1.2 |
Appears in
Sources
Fizazi K, Pagliaro L, Laplanche A, Fléchon A, Mardiak J, Geoffrois L, et al. Personalised chemotherapy based on tumour marker decline in poor prognosis germ-cell tumours (GETUG 13): a phase 3, multicentre, randomised trial. Lancet Oncol. 2014;15(13):1442-1450.
Fizazi K, Le Teuff G, Fléchon A, Pagliaro L, Mardiak J, Geoffrois L, et al. Personalized Chemotherapy on the Basis of Tumor Marker Decline in Poor-Prognosis Germ-Cell Tumors: Updated Analysis of the GETUG-13 Phase III Trial. J Clin Oncol. 2024;42(28):3270-3276.