Table 1.
Genetic changes in EGFR and other genes associated with response to depatux-m + TMZ
| EGFR mutation/Gene | Treatment | HR | 95% CI | Pr(>|z|) | n | events | survival (months) | |
|---|---|---|---|---|---|---|---|---|
| Any mutation | TMZ|CCNU | 28 | 26 | 6.8 | ||||
| depatux-m | 0.751 | 0.444 | 1.272 | 0.287 | 37 | 31 | 8.4 | |
| TMZ+depatux-m | 0.495 | 0.283 | 0.865 | 0.014 | 33 | 26 | 11.7 | |
| Hotspot mutation | TMZ|CCNU | 15 | 14 | 7.1 | ||||
| depatux-m | 1.058 | 0.530 | 2.113 | 0.873 | 21 | 20 | 7.0 | |
| TMZ+depatux-m | 0.510 | 0.247 | 1.055 | 0.070 | 21 | 16 | 10.5 | |
| A289 | TMZ|CCNU | 8 | 8 | 7.5 | ||||
| depatux-m | 0.799 | 0.313 | 2.037 | 0.638 | 11 | 11 | 6.2 | |
| TMZ+depatux-m | 0.386 | 0.138 | 1.082 | 0.070 | 11 | 8 | 10.4 | |
| G598 | TMZ|CCNU | 4 | 4 | 4.2 | ||||
| depatux-m | 1 | 0 | NA | |||||
| TMZ+depatux-m | 0.254 | 0.027 | 2.370 | 0.229 | 2 | 1 | 7.8 | |
| R108 | TMZ|CCNU | 3 | 2 | 5.2 | ||||
| depatux-m | 1.814 | 0.325 | 10.120 | 0.497 | 5 | 5 | 7.8 | |
| TMZ+depatux-m | 1.076 | 0.207 | 5.590 | 0.931 | 6 | 6 | 9.3 | |
| EGFRvIII absent | TMZ|CCNU | 22 | 20 | 9.1 | ||||
| depatux-m | 1.004 | 0.570 | 1.771 | 0.988 | 35 | 30 | 7.9 | |
| TMZ+depatux-m | 0.582 | 0.311 | 1.088 | 0.090 | 28 | 21 | 14.1 | |
| EGFRvIII present | TMZ|CCNU | 43 | 40 | 7.5 | ||||
| depatux-m | 0.894 | 0.553 | 1.446 | 0.649 | 33 | 29 | 7.3 | |
| TMZ+depatux-m | 0.673 | 0.412 | 1.099 | 0.114 | 33 | 27 | 9.8 | |
| ∆ex25-27 | TMZ|CCNU | 11 | 11 | 5.1 | ||||
| depatux-m | 0.285 | 0.087 | 0.937 | 0.039 | 6 | 5 | 9.4 | |
| TMZ+depatux-m | 0.255 | 0.077 | 0.846 | 0.026 | 5 | 4 | 16.9 | |
| ∆ex25-26 | TMZ|CCNU | 5 | 3 | 8.4 | ||||
| depatux-m | 1.691 | 0.399 | 7.166 | 0.476 | 6 | 5 | 5.5 | |
| TMZ+depatux-m | 0.629 | 0.104 | 3.804 | 0.614 | 3 | 2 | 14.4 | |
| ∆ex27 | TMZ|CCNU | 2 | 2 | 6.6 | ||||
| depatux-m | 2.145 | 0.117 | 39.265 | 0.607 | 1 | 1 | 3.9 | |
| TMZ+depatux-m | 0.351 | 0.031 | 3.978 | 0.398 | 2 | 2 | 14.1 | |
| C-term del | TMZ|CCNU | 2 | 2 | 6.8 | ||||
| depatux-m | 1.414 | 0.085 | 23.570 | 0.809 | 1 | 1 | 3.5 | |
| TMZ+depatux-m | 0.000 | 0.000 | Inf | 0.999 | 3 | 1 | NA | |
| C-term SNV | TMZ|CCNU | 3 | 3 | 5.1 | ||||
| depatux-m | 0.107 | 0.009 | 1.278 | 0.077 | 4 | 2 | 17.8 | |
| TMZ+depatux-m | 0.077 | 0.005 | 1.192 | 0.067 | 3 | 1 | NA | |
| all-C-term | TMZ|CCNU | 16 | 14 | 5.1 | ||||
| depatux-m | 0.514 | 0.229 | 1.155 | 0.107 | 15 | 12 | 8.5 | |
| TMZ+depatux-m | 0.309 | 0.130 | 0.735 | 0.008 | 13 | 9 | 16.9 | |
| all C-term trunc | TMZ|CCNU | 13 | 13 | 5.1 | ||||
| depatux-m | 0.480 | 0.181 | 1.271 | 0.140 | 8 | 7 | 8.8 | |
| TMZ+depatux-m | 0.175 | 0.054 | 0.574 | 0.004 | 7 | 4 | 18.3 | |
| PTEN all | TMZ|CCNU | 16 | 16 | 8.4 | ||||
| depatux-m | 0.692 | 0.353 | 1.353 | 0.282 | 23 | 19 | 8.4 | |
| TMZ+depatux-m | 0.499 | 0.241 | 1.034 | 0.061 | 20 | 15 | 10.2 | |
| PTEN HD | TMZ|CCNU | 14 | 13 | 5.4 | ||||
| depatux-m | 1.291 | 0.540 | 3.088 | 0.566 | 9 | 9 | 5.5 | |
| TMZ+depatux-m | 0.392 | 0.125 | 1.229 | 0.108 | 7 | 6 | 8.2 | |
| PTEN SNV | TMZ|CCNU | 13 | 13 | 8.8 | ||||
| depatux-m | 0.876 | 0.636 | 1.207 | 0.417 | 18 | 15 | 8.7 | |
| TMZ+depatux-m | 0.659 | 0.475 | 0.914 | 0.013 | 15 | 11 | 11.0 | |
| ARID1A SNV | TMZ|CCNU | 2 | 2 | 2.6 | ||||
| depatux-m | 0.541 | 0.086 | 3.410 | 0.513 | 5 | 5 | 5.4 | |
| TMZ+depatux-m | 0.139 | 0.015 | 1.258 | 0.079 | 5 | 3 | 16.6 | |
| ARID1A LOH | TMZ|CCNU | 3 | 3 | 10.5 | ||||
| depatux-m | 1 | 0 | NA | |||||
| TMZ+depatux-m | 0.286 | 0.047 | 1.745 | 0.175 | 6 | 5 | 15.1 | |
| AIRD1A SNV+LOH | TMZ|CCNU | 5 | 5 | 4.2 | ||||
| depatux-m | 0.572 | 0.158 | 2.070 | 0.395 | 6 | 5 | 8.2 | |
| TMZ+depatux-m | 0.269 | 0.075 | 0.961 | 0.043 | 11 | 8 | 15.4 | |
| RP11.770J1.4 | TMZ|CCNU | 10 | 10 | 6.7 | ||||
| depatux-m | 0.831 | 0.379 | 1.821 | 0.643 | 19 | 17 | 8.4 | |
| TMZ+depatux-m | 0.322 | 0.100 | 1.036 | 0.057 | 8 | 4 | 14.8 | |
| DHFR | TMZ|CCNU | 28 | 27 | 9.5 | ||||
| depatux-m | 1.003 | 0.599 | 1.677 | 0.992 | 36 | 32 | 7.9 | |
| TMZ+depatux-m | 0.587 | 0.345 | 1.001 | 0.050 | 36 | 28 | 11.7 |
OS = Median overall survival. Hotspot mutations are defined as amino acid changes present in at least four samples and involve amino acids, A289, G598, R222, R108, K261, P266, H304, H773, V774, and/or M1002.