BA06 30894
Needs reviewInternational phase III trial assessing neoadjuvant cisplatin, methotrexate, and vinblastine chemotherapy for muscle-invasive bladder cancer (MRC/EORTC BA06 30894)
Phase 3N = 976
- Population
- Patients with T2 G3, T3, T4a, N0-NX, or M0 transitional-cell carcinoma of the bladder undergoing curative cystectomy or full-dose external-beam radiotherapy
- Design
- International multicentre randomised phase 3 trial: three cycles of neoadjuvant cisplatin, methotrexate and vinblastine (CMV, with folinic acid rescue) or no neoadjuvant chemotherapy, before curative cystectomy or full-dose external-beam radiotherapy. 976 patients recruited between 1989 and 1995. Median follow-up of patients still alive was 4.0 years at the 1999 report and 8.0 years at the 2011 report. The 1999 report states that a 10% improvement in 3-year survival was judged necessary for introduction into routine use.
- Arms
- No neoadjuvant chemotherapy (control, n = 485): No neoadjuvant chemotherapy, then cystectomy or radiotherapy
- CMV (experimental, n = 491): Three cycles of neoadjuvant cisplatin, methotrexate and vinblastine with folinic acid rescue, then cystectomy or radiotherapy
- People
- International Collaboration of Trialists, International Collaboration of Trialists
Show the numbers
| Endpoint | Analysis | CMV | No neoadjuvant chemotherapy | Effect |
|---|---|---|---|---|
| OSRandomised patients (analysis population not stated in the abstract) | primaryInternational 1999 | median 44 months; 55.5% at 3 y | median 37.5 months; 50% at 3 y | P=0.075 (log-rank)Calculated absolute difference in 3-year survival 5.5% (95% CI -0.5 to 11.0). Median follow-up of patients still alive 4.0 years. Chemotherapy mortality 1% and operative (cystectomy) mortality 3.7%. |
| OSRandomised patients (analysis population not stated in the abstract) | long term-updatemedian follow-up 8 yearsInternational 2011 | 36% at 10 y | 30% at 10 y | HR 0.84 (95% CI 0.72–0.99)P=0.037The abstract reports the 10-year survival values as the increase from 30% to 36% corresponding to the hazard ratio. |
| Endpoint | Analysis | CMV | No neoadjuvant chemotherapy | Effect |
|---|---|---|---|---|
| OSRandomised patients (analysis population not stated in the abstract) | primaryInternational 1999 | median 44 months; 55.5% at 3 y | median 37.5 months; 50% at 3 y | P=0.075 (log-rank)Calculated absolute difference in 3-year survival 5.5% (95% CI -0.5 to 11.0). Median follow-up of patients still alive 4.0 years. Chemotherapy mortality 1% and operative (cystectomy) mortality 3.7%. |
| OSRandomised patients (analysis population not stated in the abstract) | long term-updatemedian follow-up 8 yearsInternational 2011 | 36% at 10 y | 30% at 10 y | HR 0.84 (95% CI 0.72–0.99)P=0.037The abstract reports the 10-year survival values as the increase from 30% to 36% corresponding to the hazard ratio. |
Data table
| Endpoint | HR | 95% CI |
|---|---|---|
| OS | 0.84 | 0.72–0.99 |
- No neoadjuvant chemotherapy (control)
- CMV (experimental)
Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.
Data table (modelled values)
| Months | No neoadjuvant chemotherapy | CMV |
|---|---|---|
| 0 | 100.0% | 100.0% |
| 28 | 59.6% | 64.3% |
| 55 | 36.2% | 42.0% |
| 83 | 21.6% | 27.0% |
| 110 | 13.1% | 17.7% |
Appears in
Sources
International Collaboration of Trialists. Neoadjuvant cisplatin, methotrexate, and vinblastine chemotherapy for muscle-invasive bladder cancer: a randomised controlled trial. Lancet. 1999;354(9178):533-40.
International Collaboration of Trialists, Griffiths G, Hall R, Sylvester R, Raghavan D, Parmar MK. International phase III trial assessing neoadjuvant cisplatin, methotrexate, and vinblastine chemotherapy for muscle-invasive bladder cancer: long-term results of the BA06 30894 trial. J Clin Oncol. 2011;29(16):2171-7.