Table 4.
Overall incidences of adverse events of special interest for bevacizumab (all grades and grade ≥3)
| AESI/Adverse Event, n (%) | BEV + RT/TMZ (n = 461) |
Plb + RT/TMZ (n = 450) |
||
|---|---|---|---|---|
| All Grades | Grade ≥3 | All Grades | Grade ≥3 | |
| Total patients with at least one AESI | 349 (75.7) | 150 (32.5) | 204 (45.3) | 71 (15.8) |
| Bleeding (cerebral hemorrhage) | 15 (3.3) | 9 (2.0) | 9 (2.0) | 4 (0.9) |
| Resolved | 11 (73.3) | 8 (88.9) | 5 (55.6) | 1 (25.0) |
| Unresolved | 4 (26.7) | 1 (11.1) | 3 (33.3) | 2 (50.0) |
| Death | 0 | 0 | 1a (11.1) | 1a (25.0) |
| Other bleeding (including mucocutaneous bleeding) | 171 (37.1) | 6 (1.3) | 88 (19.6) | 4 (0.9) |
| Resolved | 145 (84.8) | 4 (66.7) | 69 (78.4) | 2 (50.0) |
| Unresolved | 43 (25.1) | 1 (16.7) | 22 (25.0) | 1 (25.0) |
| Death | 1b (0.6) | 1b (16.7) | 1c (1.1) | 1c (25.0) |
| Wound-healing complications | 32 (6.9) | 15 (3.3) | 21 (4.7) | 7 (1.6) |
| Resolved | 27 (84.4) | 11 (73.3) | 19 (90.5) | 7 (100.0) |
| Unresolved | 7 (21.9) | 3 (20.0) | 2 (9.5) | 0 |
| Death | 1 (3.1) | 1 (6.7) | 0 | 0 |
| ATEsd | 27 (5.9) | 23 (5.0) | 7 (1.6) | 6 (1.3) |
| Resolved with sequelae | 11 (40.7) | 11 (47.8) | 2 (28.6) | 2 (33.3) |
| Resolved without sequelae | 9 (33.3) | 6 (26.1) | 1 (14.3) | 1 (16.7) |
| Unresolved | 7 (25.9) | 6 (26.1) | 3 (42.9) | 2 (33.3) |
| Death | 1 (3.7) | 1 (4.3) | 1 (14.3) | 1 (16.7) |
| Venous thromboembolic events | 38 (8.2) | 35 (7.6) | 43 (9.6) | 36 (8.0) |
| Resolved | 26 (68.4) | 23 (65.7) | 22 (51.2) | 17 (47.2) |
| Unresolved | 11 (28.9) | 11 (31.4) | 21 (48.8) | 19 (52.8) |
| Death | 3e (7.9) | 3e (8.6) | 1 (2.3) | 1 (2.8) |
| Hypertension | 181 (39.3) | 52 (11.3) | 57 (12.7) | 10 (2.2) |
| Resolved | 131 (72.4) | 35 (67.3) | 46 (80.7) | 7 (70.0) |
| Unresolved | 62 (34.3) | 19 (36.5) | 13 (22.8) | 3 (30.0) |
| Death | 0 | 0 | 0 | 0 |
| Proteinuria | 72 (15.6) | 25 (5.4) | 19 (4.2) | 0 |
| Resolved | 49 (68.1) | 14 (56.0) | 16 (84.2) | 0 |
| Unresolved | 38 (52.8) | 12 (48.0) | 4 (21.1) | 0 |
| Death | 0 | 0 | 0 | 0 |
| GI perforation (including GI fistula/abscess) | 8 (1.7) | 5 (1.1) | 2 (0.4) | 1 (0.2) |
| Resolved | 6 (75.0) | 4 (80.0) | 0 | 0 |
| Unresolved | 1 (12.5) | 0 | 2 (100.0) | 1 (100.0) |
| Death | 1 (12.5) | 1 (20.0) | 0 | 0 |
| Abscesses and fistulae (non GI) | 2 (0.4) | 2 (0.4) | 3 (0.7) | 3 (0.7) |
| Resolved | 2 (100.0) | 2 (100.0) | 3 (100.0) | 3 (100.0) |
| Unresolved | 0 | 0 | 0 | 0 |
| Death | 0 | 0 | 0 | 0 |
| Congestive heart failure | 2 (0.4) | 2 (0.4) | 1 (0.2) | 0 |
| Resolved | 1 (50.0) | 1 (50.0) | 1 (100.0) | 0 |
| Unresolved | 1 (50.0) | 1 (50.0) | 0 | 0 |
| Death | 0 | 0 | 0 | 0 |
Abbreviations: AESI, adverse event of special interest; BEV, bevacizumab; Plb, placebo; RT, radiotherapy; TMZ, temozolomide; ATE, arterial thromboembolic event; GI, gastrointestinal; MedDRA, Medical Dictionary for Regulatory Activities.
In cases resolved/unresolved, multiple occurrences of the same AE in one patient are included. There were no reports of posterior reversible encephalopathy syndrome.
aCerebrovascular accident, which codes to the standard MedDRA query of “cerebral hemorrhage.” However, medical review identified this event to be of ischemic origin.
bTumor hemorrhage.
cGI hemorrhage.
d21/27 patients (78%) in the bevacizumab arm experienced a serious ATE and 5/7 patients (71%) in the placebo arm experienced a serious ATE.
eOne patient stopped trial treatment on day 49 of the concurrent phase, before receiving off-protocol anticancer treatment with 2 cycles of BEV from day 78 to day 120 and 2 cycles of TMZ from day 78 to day 134. The death occurred in the follow-up period (>90 d from the last dose but within 6 mo of the last dose).