SWOG S0777
Bortezomib with lenalidomide and dexamethasone versus lenalidomide and dexamethasone alone in patients with newly diagnosed myeloma without intent for immediate autologous stem-cell transplant (SWOG S0777): a randomised, open-label, phase 3 trial
Phase 3N = 525NCT00644228
- Population
- Patients aged 18 years and older with newly diagnosed multiple myeloma without intent for immediate autologous stem-cell transplant (randomisation stratified by intent to transplant).
- Design
- Randomised (1:1), open-label phase 3 trial in patients aged 18 years and older with newly diagnosed myeloma, CRAB criteria and measurable disease, ECOG performance status 0-3, from SWOG and NCTN institutions; randomisation stratified by International Staging System stage and intent to transplant. VRd: eight 21-day cycles of bortezomib 1.3 mg/m2 intravenously on days 1, 4, 8 and 11, lenalidomide 25 mg on days 1-14 and dexamethasone 20 mg on days 1, 2, 4, 5, 8, 9, 11 and 12. Rd: six 28-day cycles of lenalidomide 25 mg on days 1-21 and dexamethasone 40 mg on days 1, 8, 15 and 22. Primary endpoint progression-free survival by a prespecified one-sided stratified log-rank test at a significance level of 0.02; analyses were intention to treat.
- Primary endpoint
- PFS
- Arms
- Bortezomib, lenalidomide, dexamethasone (VRd) (experimental, n = 264): Eight 21-day cycles of bortezomib, lenalidomide and dexamethasone
- Lenalidomide, dexamethasone (Rd) (control, n = 261): Six 28-day cycles of lenalidomide and dexamethasone
- People
- Durie BGM, SWOG
PFSHR 0.712Δ median PFS+13 monthsOSHR 0.709 (95% CI 0.524–0.959)Δ median OS+11 monthsΔ ORR+10 points
Show the numbers
| Endpoint | Analysis | Bortezomib, lenalidomide, dexamethasone (VRd) | Lenalidomide, dexamethasone (Rd) | Effect |
|---|---|---|---|---|
| PFSIntention to treat as stated in the abstract (the full text says all eligible patients were analysed; 21 VRd and 31 Rd patients were deemed ineligible) | primaryDurie 2017 | median 43 months | median 30 months | HR 0.712P=0.0018 (one-sided)Stratified hazard ratio 0.712 with a 96% confidence interval of 0.56 to 0.906 (prespecified one-sided significance level of 0.02), not a 95% interval. 21 patients in the VRd group and 31 in the Rd group were deemed ineligible. |
| OSIntention to treat as stated in the abstract (the full text says all eligible patients were analysed; 21 VRd and 31 Rd patients were deemed ineligible) | primaryDurie 2017 | median 75 months | median 64 months | HR 0.709 (95% CI 0.524–0.959)P=0.025 (two-sided) |
| ORRPatients assessable for response (216 VRd, 214 Rd)Partial response or better. | primaryDurie 2017 | 82% | 72% | 176 of 216 versus 153 of 214. Complete response or better 16% (34/216) versus 8% (18/214). Grade 3 or higher adverse events 82% (198 of 241) versus 75% (169 of 226); 23% versus 10% discontinued induction because of adverse events. |
| Endpoint | Analysis | Bortezomib, lenalidomide, dexamethasone (VRd) | Lenalidomide, dexamethasone (Rd) | Effect |
|---|---|---|---|---|
| PFSIntention to treat as stated in the abstract (the full text says all eligible patients were analysed; 21 VRd and 31 Rd patients were deemed ineligible) | primaryDurie 2017 | median 43 months | median 30 months | HR 0.712P=0.0018 (one-sided)Stratified hazard ratio 0.712 with a 96% confidence interval of 0.56 to 0.906 (prespecified one-sided significance level of 0.02), not a 95% interval. 21 patients in the VRd group and 31 in the Rd group were deemed ineligible. |
| OSIntention to treat as stated in the abstract (the full text says all eligible patients were analysed; 21 VRd and 31 Rd patients were deemed ineligible) | primaryDurie 2017 | median 75 months | median 64 months | HR 0.709 (95% CI 0.524–0.959)P=0.025 (two-sided) |
| ORRPatients assessable for response (216 VRd, 214 Rd)Partial response or better. | primaryDurie 2017 | 82% | 72% | 176 of 216 versus 153 of 214. Complete response or better 16% (34/216) versus 8% (18/214). Grade 3 or higher adverse events 82% (198 of 241) versus 75% (169 of 226); 23% versus 10% discontinued induction because of adverse events. |
Data table
| Endpoint | HR | 95% CI |
|---|---|---|
| OS | 0.709 | 0.524–0.959 |
- Bortezomib, lenalidomide, dexamethasone (VRd) (experimental)
- Lenalidomide, dexamethasone (Rd) (control)
Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.
Data table (modelled values)
| Months | Bortezomib, lenalidomide, dexamethasone (VRd) | Lenalidomide, dexamethasone (Rd) |
|---|---|---|
| 0 | 100.0% | 100.0% |
| 27 | 64.7% | 53.6% |
| 54 | 41.9% | 28.7% |
| 81 | 27.1% | 15.4% |
| 108 | 17.5% | 8.2% |
- Bortezomib, lenalidomide, dexamethasone (VRd) (experimental)
- Lenalidomide, dexamethasone (Rd) (control)
Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.
Data table (modelled values)
| Months | Bortezomib, lenalidomide, dexamethasone (VRd) | Lenalidomide, dexamethasone (Rd) |
|---|---|---|
| 0 | 100.0% | 100.0% |
| 47 | 64.8% | 60.1% |
| 94 | 41.9% | 36.1% |
| 141 | 27.2% | 21.7% |
| 188 | 17.6% | 13.1% |
Appears in
Sources
Durie BGM, Hoering A, Abidi MH, Rajkumar SV, Epstein J, Kahanic SP, et al. Bortezomib with lenalidomide and dexamethasone versus lenalidomide and dexamethasone alone in patients with newly diagnosed myeloma without intent for immediate autologous stem-cell transplant (SWOG S0777): a randomised, open-label, phase 3 trial. Lancet. 2017;389(10068):519-527.