Table 1. Key Clinical Inputs.
| Parameters | Values |
|---|---|
| Clinical inputs | |
| Survival model of PFS in the full cohort | |
| Spline model for ipilimumab (knot = 2)4,6 | gamma0 = −2.1172; gamma1 = 0.9218; gamma2 = −0.5233; gamma3 = 0.5493 |
| Spline model for pembrolizumab (knot = 1)4 | gamma0 = −6.868; gamma1 = 2.4958; gamma2 = 0.1094 |
| Spline model for nivolumab (knot = 2)6 | gamma0 = −12.6277; gamma1 = 6.0451; gamma2 = 1.302; gamma3 = −0.7823 |
| MCM with log-logistic for nivolumab plus ipilimumab6 | theta = 0.3505; shape = 1.455; scale = 21.6629 |
| Survival model of OS in the full cohort | |
| Spline model for ipilimumab (knot = 2)4,6 | gamma0 = −2.6989; gamma1 = 0.1587; gamma2 = −0.1046; gamma3 = 0.1478 |
| MCM with log-logistic for nivolumab4 | theta = 0.3191; shape = 1.3386; scale = 73.7747 |
| Spline model for pembrolizumab (knot = 2)6 | gamma0 = −5.7132; gamma1 = 1.2744; gamma2 = −0.0711; gamma3 = 0.1494 |
| MCM with lognormal for nivolumab plus ipilimumab6 | theta = 0.438; meanlog = 4.0933; sdlog = 1.3611 |
| Survival model of PFS in BRAF pathogenic variant | |
| Spline model for dabrafenib plus trametinib (knot = 1)5 | gamma0 = −5.4308; gamma1 = 3.2751; gamma2 = 0.0947 |
| Spline model for ipilimumab (knot = 2)6 | gamma0 = −11.8106; gamma1 = 5.1428; gamma2 = 1.1102; gamma3 = −0.7594 |
| Spline model for nivolumab (knot = 2)6 | gamma0 = −11.5176; gamma1 = 4.7603; gamma2 = 1.2352; gamma3 = −0.7906 |
| MCM with log-logistic for nivolumab plus ipilimumab6 | theta = 0.3705; shape = 1.4486; scale = 24.9668 |
| Survival model of OS in BRAF pathogenic variant | |
| MCM with log-logistic for dabrafenib plus trametinib5 | theta = 0.2831; shape = 1.9332; scale = 24.298 |
| Spline model for ipilimumab (knot = 2)6 | gamma0 = −2.6989; gamma1 = 0.1587; gamma2 = −0.1046; gamma3 = 0.1478 |
| Spline model for nivolumab (knot = 2)6 | gamma0 = −5.7132; gamma1 = 1.2744; gamma2 = −0.0711; gamma3 = 0.1494 |
| MCM with lognormal for nivolumab plus ipilimumab6 | theta = 0.438; meanlog = 4.0933; sdlog = 1.3611 |
| Survival model of PFS in no BRAF pathogenic variant | |
| Spline model for ipilimumab (knot = 1)6 | gamma0 = −6.4446; gamma1 = 3.5309; gamma2 = 0.0783 |
| Spline model for nivolumab (knot = 2)6 | gamma0 = −8.5331; gamma1 = 3.5396; gamma2 = 0.6453; gamma3 = −0.4492 |
| Spline model for ipilimumab (knot = 1)6 | gamma0 = −6.2832; gamma1 = 2.0604; gamma2 = 0.1182 |
| Survival model of OS in no BRAF pathogenic variant | |
| Gompertz model for ipilimumab (knot = 1)6 | shape = −0.0057; rate = 0.0104 |
| MCM with lognormal for nivolumab6 | theta = 0.2401; meanlog = 4.4362; sdlog = 1.6392 |
| MCM with lognormal for nivolumab plus ipilimumab6 | theta = 0.429; meanlog = 3.8882; sdlog = 1.2248 |
| HR of pembrolizumab vs ipilimumab in subgroups | |
| PFS in no BRAF pathogenic variant (pembrolizumab every 3 wk)4 | Expected value (range): 0.57 (0.43 to 0.75); lognormal distribution (log-mean = −0.562; log-se = 2.506)a |
| OS in no BRAF pathogenic variant (pembrolizumab every 3 wk)4 | Expected value (range): 0.73 (0.58 to 0.93); lognormal distribution (log-mean = −0.315; log-se = 2.416)a |
| PFS in BRAF pathogenic variant (pembrolizumab every 2 wk)4 | Expected value (range): 0.54 (0.32 to 0.91); lognormal distribution (log-mean = −0.616; log-se = 1.894)a |
| OS in BRAF pathogenic variant (pembrolizumab every 2 wk)4 | Expected value (range): 0.70 (0.44 to 1.11); lognormal distribution (log-mean = −0.357; log-se = 1.767)a |
| Prevalence of BRAF pathogenic variant4,6,11,12 | Expected value (range): 0.35 (0.143 to 0.6); beta distribution (α = 5.9; β = 10.9)a |
Abbreviations: HR, hazard ratio; MCM, mix cure model; OS, overall survival; PFS, progression-free survival.
a
The range is the reported or estimated 95% CI.