Table 1.
Response to treatment in orthotopic models of glioblastoma patient-derived xenografts*
| GBM lines | Treatment start, d |
Median survival (95% CI), d | Survival ratio† | |||||
|---|---|---|---|---|---|---|---|---|
| Placebo | Veliparib | TMZ | TMZ +veliparib |
TMZ | TMZ+ veliparib |
Δ-ratio‡ | ||
| MGMT unmethylated | ||||||||
| GBM6 | 12 | 41 (13 to 44) |
NA | 58 (50 to 58) |
64§ (57 to 69) |
1.41 | 1.56 | 0.15 |
| GBM14R | 6 | 27 (21 to 27) |
NA | 62 (27 to 69) |
69 (32 to 81) |
2.30 | 2.56 | 0.26 |
| GBM28A | 10 | 26 (26 to 31) |
NA | 33 (28 to 40) |
33 (26 to 62) |
1.27 | 1.27 | 0 |
| GBM43 | 7 | 14 (14 to 22) |
NA | 61 (53 to 65) |
39 (14 to 39) |
4.36 | 2.79 | -1.57 |
| GBM79 | 5 | 30 (29 to 31) |
NA | 32 (29 to 33) |
31 (29 to 31) |
1.07 | 1.03 | -0.04 |
| GBM122 | 63 | 80n=9
(66 to 96) |
82 (72 to 87) |
124 (90 to 149) |
140 (63 to 156) |
1.55 | 1.75 | 0.20 |
| MGMT hypermethylated | ||||||||
| GBM5 | 19 | 103n=9
(78 to 107) |
106n=9
(58 to 114) |
185 (19 to 267) |
268 (19 to 303) |
1.80 | 2.60 | 0.80 |
| GBM8 | 14 | 59 (49 to 61) |
52 (45 to 55) |
260 (160 to 296) |
231n=9
(146 to 314) |
4.41 | 3.91 | -0.50 |
| GBM12 | 4 | 15 (15 to 17) |
NA | 59 (3 to 62) |
189§ (75 to 257) |
3.93 | 12.60 | 8.67 |
| GBM15 | 34 | 71 (62 to 79) |
69 (61 to 72) |
249 (116 to 350) |
438 (171 to 452) |
3.51 | 6.17 | 2.66 |
| GBM22 | 7 | 20 (18 to 22) |
19 (17 to 32) |
58 (51 to 67) |
94§ (11 to 222) |
2.90 | 4.70 | 1.80 |
| GBM39 | 17 | 28n=8
(27 to 28) |
30 (26 to 31) |
138 (109 to 141) |
288§,n=7
(85 to 327) |
4.93 | 10.29 | 5.36 |
| GBM46R | 23 | 34 (25 to 45) |
38 (29 to 45) |
36 (23 to 43) |
49 (23 to 57) |
1.06 | 1.44 | 0.38 |
| GBM59 | 16 | 42n=20
(38 to 44) |
NA | 100n=20
(80 to 131) |
182n=20
(122 to 271) |
2.38 | 4.33 | 1.95 |
| GBM61 | 14 | 236 (152 to 278) |
315 (179 to 439) |
331 (125 to 465) |
435 (328 to 456) |
1.40 | 1.84 | 0.44 |
| GBM63 | 47 | 82n=9
(77 to 141) |
95 (76 to 117) |
263 (103 to 289) |
276 (224 to 294) |
3.21 | 3.37 | 0.16 |
| GBM76R | 17 | 77 (73 to 78) |
76 (73 to 78) |
216 (158 to 259) |
317§ (198 to 349) |
2.81 | 4.11 | 1.31 |
| GBM84 | 26 | 56 (46 to 67) |
58 (36 to 68) |
191 (159 to 234) |
219 (153 to 267) |
3.41 | 3.91 | 0.50 |
| GBM85 | 25 | 79n=9
(54 to 109) |
85 (64 to 101) |
233 (27 to 303) |
270 (211 to 325) |
2.95 | 3.42 | 0.47 |
| GBM102R | 25 | 71.5 (66 to 75) |
69 (65 to 69) |
160 (145 to 169) |
180§ (160 to 223) |
2.24 | 2.52 | 0.28 |
| GBM114 | 53 | 82 (74 to 93) |
95 (79 to 104) |
234 173 to 245 |
235 (84 to 245) |
2.85 | 2.87 | 0.02 |
| GBM115 | 23 | 140.5 (93 to 194) |
167 (134 to 210) |
173 (92 to 217) |
169 (116 to 187) |
1.23 | 1.20 | -0.03 |
| GBM116 | 25 | 61n=9
(42 to 219) |
59.5 (48 to 69) |
339 (140 to 366) |
343 (218 to 366) |
5.56 | 5.62 | 0.06 |
| GBM117 | 33 | 64.5 (60 to 91) |
62 (55 to 76) |
289 (199 to 328) |
279 (93 to 328) |
4.48 | 4.33 | -0.15 |
| GBM143R | 13 | 53.5 (38 to 71) |
56 (48 to 60) |
184 (21 to 202) |
183 (139 to 229) |
3.44 | 3.42 | -0.02 |
| GBM151 | 42 | 57 (54 to 63) |
58 (54 to 71) |
288 (103 to 423) |
317 (103 to 343) |
5.05 | 5.56 | 0.51 |
| MGMT methylation indeterminate | ||||||||
| GBM75 | 18 | 52n=9
(36 to 73) |
55 (35 to 59) |
254 (178 to 268) |
318 (235 to 326) |
4.88 | 6.11 | 1.23 |
| MGMT deleted | ||||||||
| GBM28B | 12 | 25 (23 to 25) |
26 (23 to 26) |
90 (35 to 91) |
124§ (96 to 268) |
3.60 | 4.96 | 1.36 |
* Each treatment group had 10 mice, with exceptions indicated by the superscript. CI = confidence interval; MGMT = O 6-methylguanine DNA methyltransferase; NA = not available; R = tumor line was established from a recurrent tumor; TMZ = temozolomide.
† Survival ratio was calculated by dividing the median survival in TMZ or TMZ+veliparib groups by median survival in placebo group.
‡ Δ-ratio was the difference in survival ratios between TMZ+velparib and TMZ groups.
§ Two-sided log-rank statistic P < .05 comparing median survival between TMZ vs TMZ+veliparib groups.