| Progression-free survival |
| Intervention |
Comparator |
HR |
95% CI |
ln(HR) |
SE |
pvalue |
| Dabrafenib |
DTIC |
0.37b |
0.24–0.58 |
–0.99 |
0.23 |
<0.0001 |
| Trametinib |
0.44b |
0.28–0.69 |
–0.82 |
0.23 |
<0.0001 |
| Vemurafenib |
0.38b |
0.32–0.46 |
–0.97 |
0.09 |
<0.001 |
| Ipilimumab+DTICa,c |
0.76b |
0.63–0.93 |
–0.27 |
0.10 |
0.01 |
| Temozolomidec |
0.92b |
0.80–1.06 |
–0.08 |
0.07 |
0.27 |
| Overall survival |
| Intervention |
Comparison |
Random-effects model (D-L) |
p value |
| HR |
95% CI |
ln(HR) |
SE |
| Dabrafenibd |
DTIC |
0.55e |
0.21–1.43 |
–0.60 |
0.49 |
- |
| Trametinibd |
0.56e |
0.30–1.05 |
–0.58 |
0.32 |
- |
| Vemurafenibf |
0.64e |
0.53–0.78 |
–0.45 |
0.10 |
<0.0001 |
| Ipilimumab+DTICg |
0.72e |
0.59–0.87 |
–0.33 |
0.10 |
<0.001 |
| Temozolomideh |
1.00e |
0.86–1.17 |
0.00 |
0.08 |
0.99 |
| Overall response rate |
| Intervention |
Comparison |
RR |
95% CI low |
L ln(RR) |
SE |
pvalue |
| Dabrafenib |
DTIC |
2.47 |
1.56–3.91 |
0.90 |
0.23 |
< 0.001 |
| Trametinib |
2.10 |
0.97–4.54 |
0.74 |
0.39 |
0.06 |
| Vemurafenib |
6.64 |
4.63–9.52 |
1.89 |
0.18 |
<0.001 |
| Ipilimumab+DTIC |
1.47 |
0.92–2.35 |
0.39 |
0.24 |
0.10 |
| Temozolomide |
1.53 |
1.04–2.25 |
0.43 |
0.20 |
0.03 |
| Complete response |
| Intervention |
Comparison |
RR |
95% CI low |
L n(RR)ln( RR) |
SE |
pvalue |
| Dabrafenib |
DTIC |
1.43 |
0.50–4.10 |
0.36 |
0.54 |
0.50 |
| Trametinib |
3.84 |
0.20–73.06 |
1.34 |
1.50 |
0.37 |
| Vemurafenib |
4.76 |
1.64–13.86 |
1.56 |
0.54 |
0.004 |
| Ipilimumab+DTIC |
2.02 |
0.37–10.91 |
0.70 |
0.86 |
0.42 |
| Temozolomide |
2.01 |
0.61–6.61 |
0.70 |
0.61 |
0.25 |
| DTIC: Dacarbazine; HR: Hazard Ratio; RPSFTM: Rank Preserving Structural Failure Time Model; RR: Risk Ratio; SE: Standard Error.
aPFS assessed by an Independent Review Committee; bHazard ratios are used as reported in the study publications; cAdjusted HR reported in the study; dRPSFTM “on-treatment observed” analysis, adjusted for crossover; eAdjusted HR; fRPSFT analysis, adjusted for crossover; gHR adjusted for metastasis stage and performance status; hHR stratified for the initial performance status. HR confidence intervals estimated using log-rank test. |
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