COMBI-AD
Adjuvant dabrafenib plus trametinib versus placebo in stage III BRAF V600E/K-mutant melanoma
Phase 3N = 870NCT01682083
- Population
- Completely resected stage III melanoma with BRAF V600E or V600K mutations
- Design
- Double-blind, placebo-controlled phase 3 trial. Dabrafenib 150 mg twice daily plus trametinib 2 mg once daily, or two matched placebos, for 12 months. Primary endpoint relapse-free survival; secondary endpoints included overall survival, distant metastasis-free survival, freedom from relapse and safety.
- Primary endpoint
- RFS
- Arms
- Dabrafenib plus trametinib (experimental, n = 438): Dabrafenib 150 mg twice daily plus trametinib 2 mg once daily, 12 months
- Placebo (control, n = 432): Two matched placebo tablets, 12 months
- People
- Long GV, senior author Kirkwood JM
RFSHR 0.47 (95% CI 0.39–0.58)Δ 36-month RFS+19 pointsOSHR 0.57 (95% CI 0.42–0.79)Δ 36-month OS+9 pointsRFSHR 0.51 (95% CI 0.42–0.61)Δ 60-month RFS+16 points
Show the numbers
| Endpoint | Analysis | Dabrafenib plus trametinib | Placebo | Effect |
|---|---|---|---|---|
| RFSAll randomised patients (the abstract does not name the analysis population) | primarymedian follow-up 2.8 yearsLong 2017 | 58% at 3 y | 39% at 3 y | HR 0.47 (95% CI 0.39–0.58)P<0.001Estimated 3-year rates as published (no intervals in the abstract). |
| OSAll randomised patients (the abstract does not name the analysis population) | interimmedian follow-up 2.8 yearsLong 2017 | 86% at 3 y | 77% at 3 y | HR 0.57 (95% CI 0.42–0.79)P=0.0006The abstract states this improvement did not cross the prespecified interim analysis boundary of P=0.000019. Secondary endpoint. |
| RFSAll randomised patients (the abstract does not name the analysis population) | long term-updateDummer 2020 | 52% at 5 y (48–58%) | 36% at 5 y (32–41%) | HR 0.51 (95% CI 0.42–0.61)Median follow-up 60 months (dabrafenib plus trametinib) and 58 months (placebo); minimum 59 months. Overall survival was not analysed in this report because the required number of events had not been reached (abstract). |
| DMFSAll randomised patients (the abstract does not name the analysis population) | long term-updateDummer 2020 | 65% at 5 y (61–71%) | 54% at 5 y (49–60%) | HR 0.55 (95% CI 0.44–0.70)Reported as 'survival without distant metastasis as the site of the first relapse' in the Methods and as the percentage alive without distant metastasis in the Results. |
| Endpoint | Analysis | Dabrafenib plus trametinib | Placebo | Effect |
|---|---|---|---|---|
| RFSAll randomised patients (the abstract does not name the analysis population) | primarymedian follow-up 2.8 yearsLong 2017 | 58% at 3 y | 39% at 3 y | HR 0.47 (95% CI 0.39–0.58)P<0.001Estimated 3-year rates as published (no intervals in the abstract). |
| OSAll randomised patients (the abstract does not name the analysis population) | interimmedian follow-up 2.8 yearsLong 2017 | 86% at 3 y | 77% at 3 y | HR 0.57 (95% CI 0.42–0.79)P=0.0006The abstract states this improvement did not cross the prespecified interim analysis boundary of P=0.000019. Secondary endpoint. |
| RFSAll randomised patients (the abstract does not name the analysis population) | long term-updateDummer 2020 | 52% at 5 y (48–58%) | 36% at 5 y (32–41%) | HR 0.51 (95% CI 0.42–0.61)Median follow-up 60 months (dabrafenib plus trametinib) and 58 months (placebo); minimum 59 months. Overall survival was not analysed in this report because the required number of events had not been reached (abstract). |
| DMFSAll randomised patients (the abstract does not name the analysis population) | long term-updateDummer 2020 | 65% at 5 y (61–71%) | 54% at 5 y (49–60%) | HR 0.55 (95% CI 0.44–0.70)Reported as 'survival without distant metastasis as the site of the first relapse' in the Methods and as the percentage alive without distant metastasis in the Results. |
Data table
| Endpoint | HR | 95% CI |
|---|---|---|
| RFS | 0.47 | 0.39–0.58 |
| OS | 0.57 | 0.42–0.79 |
| RFS | 0.51 | 0.42–0.61 |
| DMFS | 0.55 | 0.44–0.7 |
Appears in
Sources
Long GV, Hauschild A, Santinami M, Atkinson V, Mandalà M, Chiarion-Sileni V, et al. Adjuvant Dabrafenib plus Trametinib in Stage III BRAF-Mutated Melanoma. N Engl J Med. 2017;377(19):1813-1823.
Dummer R, Hauschild A, Santinami M, Atkinson V, Mandalà M, Kirkwood JM, et al. Five-Year Analysis of Adjuvant Dabrafenib plus Trametinib in Stage III Melanoma. N Engl J Med. 2020;383(12):1139-1148.