TABLE 1.
Model clinical parameters.
| Parameter | Estimate | Range | Distribution | Reference |
|---|---|---|---|---|
| PFS for pembrolizumab first-line therapy | Spline (knot = 3): gamma0 = −3.340736, gamma1 = 0.955158, gamma2 = −5.802732, gamma3 = 6.926259, gamma4 = −1.171400 | — | Multivariable normal | André et al. (2020) |
| PFS for encorafenib plus cetuximab | Loglogistic: shape = 2.116512, scale = 4.660681 | — | Multivariable normal | Tabernero et al. (2021) |
| PFS for FOLFOX plus bevacizumab | Weibull: a = 1.576, b = 9.101 | — | Multivariable normal | Giantonio et al. (2007) |
| PFS for irinotecan | Spline (knot = 2): gamma0 = −2.2013510, gamma1 = 3.4960096, gamma2 = 0.5627302, gamma3 = −0.3947207 | — | Multivariable normal | Sobrero et al. (2008) |
| PFS for cetuximab plus irinotecan | Spline (knot = 3): gamma0 = −1.7244692, gamma1 = 4.5958398, gamma2 = 1.0911,644, gamma3 = −1.4293002, gamma4 = 0.6907344 | Multivariable normal | Sobrero et al. (2008) | |
| PFS for chemotherapy first-line therapy | Generalized gamma: mu = 1.81749713, sigma = 0.05360466, Q = −0.61570022 | — | Multivariable normal | André et al. (2020) |
| PFS for pembrolizumab second-line therapy | Spline (knot = 3): gamma0 = −3.4041439, gamma1 = 0.6674260, gamma2 = −4.1798710, gamma3 = 5.1161971, gamma4 = −0.9710231 | — | Multivariable normal | Le et al. (2020) |
| PFS for FOLFIRI | Spline (knot = 3): gamma0 = −1.1819358, gamma1 = 4.7007055, gamma2 = 0.7169704, gamma3 = -1.2818196, gamma4 = 0.7828784 | — | Multivariable normal | Tabernero et al. (2015) |
| PFS for FOLFOX | Generalized gamma: mu = 1.6748, sigma = 0.7089, Q = 0.3498 | — | Multivariable normal | Giantonio et al. (2007) |
| PFS for regorafenib | Spline (knot = 3): gamma0 = −4.6041562, gamma1 = 0.6411741, gamma2 = −11.4902184, gamma3 = 13.9327194, gamma4 = −2.7779302 | — | Multivariable normal | Grothey et al. (2013) |
| Median survival time in best supportive care, days | 28.5 | 14–42 | Exponential: lambda = 0.51074 | Connor et al. (2007), Christakis and Escarce (1996) |
| Proportion of patients in first-line chemotherapy arm who received FOLFOX or FOLFIRI with or without bevacizumab or cetuximab | ||||
| FOLFOX | 0.08 | — | — | André et al. (2020) |
| FOLFOX plus bevacizumab | 0.45 | — | — | André et al. (2020) |
| FOLFOX plus cetuximab | 0.03 | — | André et al. (2020) | |
| FOLFIRI | 0.11 | — | — | André et al. (2020) |
| FOLFIRI + bevacizumab | 0.25 | — | — | André et al. (2020) |
| FOLFIRI + cetuximab | 0.08 | — | — | André et al. (2020) |
| Probability of discontinuing treatment due to AE, % | ||||
| Pembrolizumab first-line therapy | 14.40 | 7.20–21.60 | Beta: a = 22, b = 131 | André et al. (2020) |
| Encorafenib plus cetuximab | 9.00 | 4.50–13.50 | Beta: a = 9,b = 91 | Tabernero et al. (2015) |
| FOLFOX plus bevacizumab | 23.40 | 11.70–35.10 | Beta: a = 23,b = 77 | Giantonio et al. (2007) |
| Irinotecan | 4.77 | 2.39–7.16 | Beta: a = 31,b = 619 | Sobrero et al. (2008) |
| Cetuximab plus irinotecan | 6.50 | 3.25–9.75 | Beta: a = 42,b = 606 | Sobrero et al. (2008) |
| Chemotherapy first-line therapy | 11.90 | 5.95–17.85 | Beta: a = 17,b = 126 | André et al. (2020) |
| Pembrolizumab second-line therapy | 6.35 | 3.18–9.53 | Beta: a = 4,b = 59 | Le et al. (2020) |
| FOLFIRI | 4.29 | 2.15–6.44 | Beta: a = 23,b = 513 | Tabernero et al. (2015) |
| FOLFOX | 23.90 | 11.95–35.85 | Beta: a = 24,b = 76 | Giantonio et al. (2007) |
| Regorafenib | 8.40 | 4.20–12.60 | Beta: a = 42,b = 458 | Grothey et al. (2013) |
| Probability of mortality due to AE, % | ||||
| Pembrolizumab first-line therapy | 0 | — | — | André et al. (2020) |
| Encorafenib plus cetuximab | 4.00 | 2–6 | Beta: a = 4,b = 96 | Tabernero et al. (2021) |
| FOLFOX plus bevacizumab | 5.00 | 2.5–7.5 | Beta: a = 5,b = 95 | Giantonio et al. (2007) |
| Irinotecan | 0.31 | 0.16–0.47 | Beta: a = 2,b = 648 | Sobrero et al. (2008) |
| Cetuximab plus irinotecan | 0.77 | 0.39–1.16 | Beta: a = 5,b = 645 | Sobrero et al. (2008) |
| Chemotherapy first-line therapy | 0.70 | 0.35–1.05 | Beta: a = 1,b = 142 | André et al. (2020) |
| Pembrolizumab second-line therapy | 0 | — | — | Le et al. (2020) |
| FOLFIRI | 2.05 | 1.03–3.08 | Beta: a = 11,b = 525 | Tabernero et al. (2015) |
| FOLFOX | 4.00 | 2–6 | Beta: a = 4,b = 96 | Giantonio et al. (2007) |
| Regorafenib | 1.60 | 0.8–2.4 | Beta: a = 8,b = 492 | Grothey et al. (2013) |
| Incidence of Grade 1 or 2 AE, % | ||||
| pembrolizumab first-line therapy | 0.41 | 0.21–0.62 | Beta: a = 41,b = 59 | André et al. (2020) |
| Encorafenib plus cetuximab | 0.41 | 0.21–0.62 | Beta: a = 40,b = 60 | Tabernero et al. (2021) |
| FOLFOX plus bevacizumab | 0.25 | 0.13–0.38 | Beta: a = 25,b = 75 | Giantonio et al. (2007) |
| Irinotecan | 0.53 | 0.27–0.80 | Beta: a = 52,b = 48 | Sobrero et al. (2008) |
| Cetuximab plus irinotecan | Sobrero et al. (2008) | |||
| Chemotherapy first-line therapy | 0.21 | 0.11–0.32 | Beta: a = 21,b = 79 | André et al. (2020) |
| Pembrolizumab second-line therapy | 0.57 | 0.29–0.86 | Beta: a = 57,b = 43 | Le et al. (2020) |
| FOLFIRI | 0.27 | 0.14–0.41 | Beta: a = 27,b = 73 | Tabernero et al. (2015) |
| FOLFOX | 0.39 | 0.20–0.59 | Beta: a = 39,b = 61 | Giantonio et al. (2007) |
| Regorafenib | 0.39 | 0.20–0.59 | Beta: a = 39,b = 61 | Grothey et al. (2013) |
| Incidence of Grade 3 or greater AE, % | ||||
| Pembrolizumab first-line therapy | 0.56 | 0.28–0.84 | Beta: a = 56,b = 44 | André et al. (2020) |
| Encorafenib plus cetuximab | 0.58 | 0.29–0.87 | Beta: a = 57,b = 43 | Tabernero et al. (2021) |
| FOLFOX plus bevacizumab | 0.75 | 0.38–1 | Beta: a = 75,b = 25 | Giantonio et al. (2007) |
| Irinotecan | 0.44 | 0.22–0.66 | Beta: a = 43,b = 57 | Sobrero et al. (2008) |
| Chemotherapy first-line therapy | 0.78 | 0.39–1.17 | Beta: a = 78,b = 22 | Sobrero et al. (2008) |
| Pembrolizumab second-line therapy | 0.13 | 0.07–0.20 | Beta: a = 13,b = 87 | André et al. (2020) |
| FOLFIRI | 0.72 | 0.36–1.08 | Beta: a = 72,b = 28 | Le et al. (2020) |
| FOLFOX | 0.61 | 0.31–0.92 | Beta: a = 61,b = 39 | Tabernero et al. (2015) |
| Regorafenib | 0.54 | 0.27–0.81 | Beta: a = 54,b = 46 | Giantonio et al. (2007) |
| Patient characteristics at baseline | Grothey et al. (2013) | |||
| Age | 63 | 24–93 | Truncated Normal: mean = 63, sd = 17.6, lower = 24, upper = 93 | André et al. (2020) |
| Male sex, % | 46 | — | — | André et al. (2020) |
| Wight, kg | ||||
| Male | 90 | — | — | CDC (2021) |
| Female | 77 | — | — | CDC (2021) |
| Body surface area, m2 | ||||
| Male | 1.9 | — | — | CDC (2021) |
| Female | 1.6 | — | — | CDC (2021) |
| BRAFV600E mutant, % | 0.22 | 0.11–0.33 | Uniform (0.11, 0.33) | André et al. (2020) |