VISTA
Bortezomib plus melphalan and prednisone for initial treatment of multiple myeloma (Velcade as Initial Standard Therapy in Multiple Myeloma)
Phase 3N = 682NCT00111319
- Population
- Previously untreated patients with symptomatic myeloma who were ineligible for high-dose therapy.
- Design
- Phase 3 trial in 682 previously untreated patients with myeloma ineligible for high-dose therapy, randomly assigned to nine 6-week cycles of melphalan 9 mg/m2 and prednisone 60 mg/m2 on days 1 to 4, alone or with bortezomib 1.3 mg/m2 (days 1, 4, 8, 11, 22, 25, 29 and 32 in cycles 1 to 4; days 1, 8, 22 and 29 in cycles 5 to 9). The primary end point was time to disease progression.
- Primary endpoint
- TTP
- Arms
- Bortezomib, melphalan, prednisone (VMP) (experimental, n = 344): Melphalan 9 mg/m2 and prednisone 60 mg/m2 days 1-4 plus bortezomib 1.3 mg/m2, nine 6-week cycles
- Melphalan, prednisone (MP) (control, n = 338): Melphalan 9 mg/m2 and prednisone 60 mg/m2 days 1-4, nine 6-week cycles
- People
- San Miguel JF
TTPHR 0.48Δ median TTP+7.4 monthsΔ ORR+36 pointsΔ CR rate+26 pointsΔ median DOR+6.8 monthsOSHR 0.61
Show the numbers
| Endpoint | Analysis | Bortezomib, melphalan, prednisone (VMP) | Melphalan, prednisone (MP) | Effect |
|---|---|---|---|---|
| TTPRandomised patients (analysis population not stated in the abstract) | primarySan 2008 | median 24 months | median 16.6 months | HR 0.48P<0.001 |
| ORRRandomised patients (analysis population not stated in the abstract)Partial response or better. | primarySan 2008 | 71% | 35% | P<0.001P<0.001 is reported in the abstract jointly for the response and complete-response comparisons. |
| CR rateRandomised patients (analysis population not stated in the abstract) | primarySan 2008 | 30% | 4% | P<0.001 |
| DORResponding patients (population not stated in the abstract) | primarySan 2008 | median 19.9 months | median 13.1 months | — |
| OSRandomised patients (analysis population not stated in the abstract) | primarySan 2008 | — | — | HR 0.61P=0.008Grade 3 events 53% versus 44% (P=0.02); grade 4 events 28% versus 27%; treatment-related deaths 1% versus 2%. |
| OSRandomised patients (updated analysis; VMP n=344, MP n=338) | long term-updatemedian follow-up 36.7 monthsMateos 2010 | 68.5% at 3 y | 54% at 3 y | HR 0.653P<0.001Median OS was not reached with VMP and was 43 months with MP. Reported as updated follow-up of the same trial with analysis of subsequent therapy. |
| Endpoint | Analysis | Bortezomib, melphalan, prednisone (VMP) | Melphalan, prednisone (MP) | Effect |
|---|---|---|---|---|
| TTPRandomised patients (analysis population not stated in the abstract) | primarySan 2008 | median 24 months | median 16.6 months | HR 0.48P<0.001 |
| ORRRandomised patients (analysis population not stated in the abstract)Partial response or better. | primarySan 2008 | 71% | 35% | P<0.001P<0.001 is reported in the abstract jointly for the response and complete-response comparisons. |
| CR rateRandomised patients (analysis population not stated in the abstract) | primarySan 2008 | 30% | 4% | P<0.001 |
| DORResponding patients (population not stated in the abstract) | primarySan 2008 | median 19.9 months | median 13.1 months | — |
| OSRandomised patients (analysis population not stated in the abstract) | primarySan 2008 | — | — | HR 0.61P=0.008Grade 3 events 53% versus 44% (P=0.02); grade 4 events 28% versus 27%; treatment-related deaths 1% versus 2%. |
| OSRandomised patients (updated analysis; VMP n=344, MP n=338) | long term-updatemedian follow-up 36.7 monthsMateos 2010 | 68.5% at 3 y | 54% at 3 y | HR 0.653P<0.001Median OS was not reached with VMP and was 43 months with MP. Reported as updated follow-up of the same trial with analysis of subsequent therapy. |
- Bortezomib, melphalan, prednisone (VMP) (experimental)
- Melphalan, prednisone (MP) (control)
Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.
Data table (modelled values)
| Months | Bortezomib, melphalan, prednisone (VMP) | Melphalan, prednisone (MP) |
|---|---|---|
| 0 | 100.0% | 100.0% |
| 15 | 64.8% | 53.5% |
| 30 | 42.0% | 28.6% |
| 45 | 27.3% | 15.3% |
| 60 | 17.7% | 8.2% |
- Bortezomib, melphalan, prednisone (VMP) (experimental)
- Melphalan, prednisone (MP) (control)
Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.
Data table (modelled values)
| Months | Bortezomib, melphalan, prednisone (VMP) | Melphalan, prednisone (MP) |
|---|---|---|
| 0 | 100.0% | 100.0% |
| 12 | 65.8% | 53.0% |
| 25 | 41.9% | 26.6% |
| 37 | 27.6% | 14.1% |
| 50 | 17.5% | 7.1% |
Appears in
Sources
San Miguel JF, Schlag R, Khuageva NK, Dimopoulos MA, Shpilberg O, Kropff M, et al. Bortezomib plus melphalan and prednisone for initial treatment of multiple myeloma. N Engl J Med. 2008;359(9):906-17.
Mateos MV, Richardson PG, Schlag R, Khuageva NK, Dimopoulos MA, Shpilberg O, et al. Bortezomib plus melphalan and prednisone compared with melphalan and prednisone in previously untreated multiple myeloma: updated follow-up and impact of subsequent therapy in the phase III VISTA trial. J Clin Oncol. 2010;28(13):2259-66.