Table 5.
Multivariable analyses of progression free survival and overall survival in stage I–IV patients with KRAS mutations favouring PI3K/Akt (G12D), Raf (G12C, G12A, G13D, Q61L/H) and Ral (G12C).
| Variable | PFS | OS | PFS | OS | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| HR | 95%CI | p | HR | 95%CI | p | HR | 95%CI | p | HR | 95%CI | p | |
| Age (years) | 1.02 | (1.00–1.03) | 0.070 | 1.02 | (1.00–1.04) | 0.027 | 1.02 | (1.00–1.04) | 0.085 | 1.01 | (0.99–1.03) | 0.200 |
| Sex | ||||||||||||
| Women | 1 (ref) | 1 (ref) | 1 (ref) | 1 (ref) | ||||||||
| Men | 1.00 | (0.75–1.35) | 0.981 | 0.88 | (0.63–1.22) | 0.431 | 0.90 | (0.64–1.25) | 0.529 | 0.69 | (0.47–1.01) | 0.054 |
| Smoking history | ||||||||||||
| Never | 1 (ref) | 1 (ref) | 1 (ref) | 1 (ref) | ||||||||
| Former/current | 1.02 | (0.36–2.88) | 0.975 | 0.93 | (0.28–3.09) | 0.911 | 1.31 | (0.40–4.33) | 0.653 | 1.34 | (0.31–5.67) | 0.695 |
| ECOG PS | ||||||||||||
| 0–1 | 1 (ref) | 1 (ref) | 1 (ref) | 1 (ref) | ||||||||
| 2 | 2.23 | (1.32–3.76) | 0.003 | 3.03 | (1.79–5.14) | <0.001 | 2.77 | (1.46–5.23) | 0.002 | 4.89 | (2.49–9.58) | <0.001 |
| 3–4 | 6.68 | (2.89–15.5) | <0.001 | 9.21 | (3.85–22.02) | <0.001 | 6.02 | (2.41–14.99) | <0.001 | 10.95 | (4.18–28.68) | <0.001 |
| Stage | ||||||||||||
| I | 1 (ref) | 1 (ref) | 1 (ref) | 1 (ref) | ||||||||
| II | 1.55 | (0.88–2.71) | 0.128 | 1.52 | (0.79–2.94) | 0.212 | 1.35 | (0.71–2.58) | 0.363 | 1.03 | (0.47–2.26) | 0.946 |
| III | 2.61 | (1.49–4.58) | 0.001 | 2.71 | (1.45–5.06) | 0.002 | 3.21 | (1.77–5.85) | <0.001 | 2.61 | (1.30–5.25) | 0.007 |
| IV | 2.74 | (1.36–5.52) | 0.005 | 3.08 | (1.50–6.32) | 0.002 | 3.24 | (1.46–7.19) | 0.004 | 1.94 | (0.80–4.71) | 0.143 |
| Surgery | ||||||||||||
| No | 1 (ref) | 1 (ref) | 1 (ref) | 1 (ref) | ||||||||
| Yes | 0.234 | (0.11–0.48) | <0.001 | 0.22 | (0.1–0.48) | <0.001 | 0.28 | (0.13–0.62) | 0.002 | 0.16 | (0.07–0.39) | <0.001 |
| Curative RT +/− CT first line | ||||||||||||
| No | 1 (ref) | 1 (ref) | 1 (ref) | 1 (ref) | ||||||||
| Yes | 0.617 | (0.30–1.27) | 0.189 | 0.35 | (0.14–0.83) | 0.017 | 0.57 | (0.26–1.28) | 0.173 | 0.22 | (0.08–0.58) | 0.002 |
| Palliative CT and/or RT first line | ||||||||||||
| No | 1 (ref) | 1 (ref) | 1 (ref) | 1 (ref) | ||||||||
| Yes | 1.56 | (1.00–2.44) | 0.052 | 1.27 | (0.77–2.09) | 0.350 | 1.15 | (0.94–2.48) | 0.089 | 1.32 | (0.78–2.24) | 0.302 |
| PI3K vs. Raf | ||||||||||||
| Raf | 1 (ref) | 1 (ref) | - | - | - | - | - | - | ||||
| PI3K | 0.903 | (0.64–1.28) | 0.570 | 0.89 | (0.60–1.30) | 0.530 | - | - | - | - | - | - |
| PI3K vs. RalA/B | ||||||||||||
| RalA/B | - | - | - | - | - | - | 1 (ref) | 1 (ref) | ||||
| PI3K | - | - | - | - | - | - | 0.94 | (0.65–1.35) | 0.720 | 0.86 | (0.58–1.29) | 0.474 |
Abbreviations: PFS, progression free survival; OS, overall survival; ref, reference; ECOG PS, Eastern Cooperative Oncology Group performance status; CT, chemotherapy; RT, radiotherapy.