MRC TE19 / EORTC 30982
Radiotherapy versus single-dose carboplatin in adjuvant treatment of stage I seminoma: a randomised trial
Phase 3N = 1,477
- Population
- Men with stage I seminoma after orchidectomy
- Design
- Randomised non-inferiority trial, 1996 to 2001, 70 hospitals in 14 countries (ISRCTN27163214). Carboplatin and radiotherapy were allocated in a 3 to 5 ratio (2011 report). Primary outcome was the relapse-free rate; the trial was powered to exclude absolute differences in 2-year rates of more than 3% (initial report) and, in the mature report, to exclude a hazard ratio of approximately 2.0, assuming a 96-97% 2-year relapse-free rate after radiotherapy. Analysis was by intention to treat and per protocol.
- Primary endpoint
- RFR
- Arms
- Radiotherapy (control, n = 904): Adjuvant radiotherapy to a para-aortic strip or dog-leg field
- Single-dose carboplatin (experimental, n = 573): One injection of carboplatin, dose 7 x (glomerular filtration rate + 25) mg (90% of this dose when the rate was estimated from creatinine clearance rather than EDTA)
- People
- Oliver RT, MRC TE19 collaborators and the EORTC 30982 collaborators
RFRHR 1.28Δ 24-month RFR+1 pointsRFRHR 1.25Δ 60-month RFR−1.3 pointsΔ Second primary GCT rate−1.42 pointsSecond primary GCT rateHR 0.22 (95% CI 0.05–0.95)
Show the numbers
| Endpoint | Analysis | Single-dose carboplatin | Radiotherapy | Effect |
|---|---|---|---|---|
| RFRRandomised patients; 885 received radiotherapy and 560 received carboplatin; the abstract reports intention-to-treat and per-protocol analyses and does not say which one these rates useCalled relapse-free survival rates in the abstract Findings; the primary outcome measure is stated as the relapse-free rate. | primarymedian follow-up 4 yearsOliver 2005 | 97.7% at 2 y (96.0–98.6%); 94.8% at 3 y (92.5–96.4%) | 96.7% at 2 y (95.3–97.7%); 95.9% at 3 y (94.4–97.1%) | HR 1.28P=0.32Hazard ratio 1.28 with a 90% confidence interval of 0.85 to 1.93, as published (not a 95% CI, so not entered in the CI field); the abstract does not name the reference arm, but the direction (carboplatin relative to radiotherapy) is consistent with the 3-year rates and with the HR of 1.25 for carboplatin in the 2011 combined analysis. Absolute differences in 2-year relapse-free rates (radiotherapy minus carboplatin): -1.0% (90% CI -2.5 to 0.5) by direct comparison of proportions and 0.9% (-0.5 to 3.0) by a hazard-ratio-based approach. One seminoma-related death occurred after radiotherapy and none after carboplatin. The authors concluded non-inferiority of carboplatin. |
| RFRRandomised patients | long term-updatemedian follow-up 6.5 yearsOliver 2011 | 94.7% at 5 y | 96% at 5 y | HR 1.25Hazard ratio 1.25 with a 90% confidence interval of 0.83 to 1.89, as published; the 90% CI of the difference (radiotherapy minus carboplatin) in 5-year rates was 0.7% to 3.5%. Non-randomised comparison within the carboplatin arm only: patients who received at least 99% of the 7 x AUC dose had a 5-year relapse-free rate of 96.1% (95% CI 93.4% to 97.7%) versus 92.6% (88.0% to 95.5%) with lower doses (HR 0.51; 95% CI 0.24 to 1.07; P=.08). The authors concluded non-inferiority of single-dose carboplatin at 7 x AUC. |
| Second primary GCT rateRandomised patients; new second primary testicular germ-cell tumours | exploratoryOliver 2005 | 0.54% (0.1–2.1%) | 1.96% (1.0–3.8%) | P=0.04Ten events after radiotherapy (all after a para-aortic strip field) and two after carboplatin. The authors describe this as preliminary data needing confirmation beyond 4 years of follow-up. |
| Second primary GCT rateRandomised patients; contralateral germ-cell tumours | long term-updatemedian follow-up 6.5 yearsOliver 2011 | — | — | HR 0.22 (95% CI 0.05–0.95)P=0.03Contralateral germ-cell tumours: 15 in the radiotherapy arm and 2 in the carboplatin arm; the hazard ratio of 0.22 is for carboplatin relative to radiotherapy (direction follows from the counts, 2 vs 15). Elevated pretreatment follicle-stimulating hormone (above 12 IU/L) was a strong predictor of contralateral tumours (HR 8.57; 95% CI 1.82 to 40.38). |
| Endpoint | Analysis | Single-dose carboplatin | Radiotherapy | Effect |
|---|---|---|---|---|
| RFRRandomised patients; 885 received radiotherapy and 560 received carboplatin; the abstract reports intention-to-treat and per-protocol analyses and does not say which one these rates useCalled relapse-free survival rates in the abstract Findings; the primary outcome measure is stated as the relapse-free rate. | primarymedian follow-up 4 yearsOliver 2005 | 97.7% at 2 y (96.0–98.6%); 94.8% at 3 y (92.5–96.4%) | 96.7% at 2 y (95.3–97.7%); 95.9% at 3 y (94.4–97.1%) | HR 1.28P=0.32Hazard ratio 1.28 with a 90% confidence interval of 0.85 to 1.93, as published (not a 95% CI, so not entered in the CI field); the abstract does not name the reference arm, but the direction (carboplatin relative to radiotherapy) is consistent with the 3-year rates and with the HR of 1.25 for carboplatin in the 2011 combined analysis. Absolute differences in 2-year relapse-free rates (radiotherapy minus carboplatin): -1.0% (90% CI -2.5 to 0.5) by direct comparison of proportions and 0.9% (-0.5 to 3.0) by a hazard-ratio-based approach. One seminoma-related death occurred after radiotherapy and none after carboplatin. The authors concluded non-inferiority of carboplatin. |
| RFRRandomised patients | long term-updatemedian follow-up 6.5 yearsOliver 2011 | 94.7% at 5 y | 96% at 5 y | HR 1.25Hazard ratio 1.25 with a 90% confidence interval of 0.83 to 1.89, as published; the 90% CI of the difference (radiotherapy minus carboplatin) in 5-year rates was 0.7% to 3.5%. Non-randomised comparison within the carboplatin arm only: patients who received at least 99% of the 7 x AUC dose had a 5-year relapse-free rate of 96.1% (95% CI 93.4% to 97.7%) versus 92.6% (88.0% to 95.5%) with lower doses (HR 0.51; 95% CI 0.24 to 1.07; P=.08). The authors concluded non-inferiority of single-dose carboplatin at 7 x AUC. |
| Second primary GCT rateRandomised patients; new second primary testicular germ-cell tumours | exploratoryOliver 2005 | 0.54% (0.1–2.1%) | 1.96% (1.0–3.8%) | P=0.04Ten events after radiotherapy (all after a para-aortic strip field) and two after carboplatin. The authors describe this as preliminary data needing confirmation beyond 4 years of follow-up. |
| Second primary GCT rateRandomised patients; contralateral germ-cell tumours | long term-updatemedian follow-up 6.5 yearsOliver 2011 | — | — | HR 0.22 (95% CI 0.05–0.95)P=0.03Contralateral germ-cell tumours: 15 in the radiotherapy arm and 2 in the carboplatin arm; the hazard ratio of 0.22 is for carboplatin relative to radiotherapy (direction follows from the counts, 2 vs 15). Elevated pretreatment follicle-stimulating hormone (above 12 IU/L) was a strong predictor of contralateral tumours (HR 8.57; 95% CI 1.82 to 40.38). |
Data table
| Endpoint | HR | 95% CI |
|---|---|---|
| Second primary GCT rate | 0.22 | 0.05–0.95 |
- Radiotherapy (control)
- Single-dose carboplatin (experimental)
Data table (modelled values)
| Months | Radiotherapy | Single-dose carboplatin |
|---|---|---|
| 0 | 100.0% | 100.0% |
| 10 | 98.5% | 99.2% |
| 19 | 97.3% | 98.4% |
| 29 | 96.3% | 96.6% |
| 39 | 95.9% | 94.8% |
Appears in
Sources
Oliver RT, Mason MD, Mead GM, von der Maase H, Rustin GJ, Joffe JK, et al. Radiotherapy versus single-dose carboplatin in adjuvant treatment of stage I seminoma: a randomised trial. Lancet. 2005;366(9482):293-300.
Oliver RT, Mead GM, Rustin GJ, Joffe JK, Aass N, Coleman R, et al. Randomized trial of carboplatin versus radiotherapy for stage I seminoma: mature results on relapse and contralateral testis cancer rates in MRC TE19/EORTC 30982 study (ISRCTN27163214). J Clin Oncol. 2011;29(8):957-62.