Table 3.
Safety Summary and Selected AEs*
| Type of AE | GC + PL (n = 233)† |
GC + BV (n = 247)‡ |
||
|---|---|---|---|---|
| No. | % | No. | % | |
| Any | 233 | 100.0 | 247 | 100.0 |
| Grades 3 to 5 | 192 | 82.4 | 221 | 89.5 |
| Grade 5 | 1 | 0.4 | 1 | 0.4 |
| Serious | 58 | 24.9 | 86 | 34.8 |
| Grades 3 to 5 | 47 | 20.2 | 72 | 29.1 |
| Leading to study drug (BV/PL) discontinuation | 11 | 4.7 | 49 | 19.8 |
| Special interest (any grade) | 198 | 85.0 | 233 | 94.3 |
| Arterial thromboembolic event (any grade) | 2 | 0.9 | 7 | 2.8 |
| Bleeding | ||||
| CNS (any grade) | 1 | 0.4 | 2 | 0.8 |
| Non-CNS (grade ≥ 3) | 2 | 0.9 | 14 | 5.7 |
| LV systolic dysfunction/CHF (grade ≥ 3) | 2 | 0.9 | 3 | 1.2 |
| Febrile neutropenia (any grade) | 4 | 1.7 | 4 | 1.6 |
| Fistula/abscess (any grade)§ | 1 | 0.4 | 4 | 1.6 |
| GI perforation (any grade) | 0 | 0.0 | 0 | 0.0 |
| Hypertension (grade ≥ 3) | 1 | 0.4 | 43 | 17.4 |
| Neutropenia (grade ≥ 4) | 51 | 21.9 | 51 | 20.6 |
| Proteinuria (grade ≥ 3) | 2 | 0.9 | 21 | 8.5 |
| RPLS (any grade) | 0 | 0.0 | 3 | 1.2‖ |
| Wound-healing complication (grade ≥ 3) | 0 | 0.0 | 2 | 0.8 |
| Venous thromboembolic event (grade ≥ 3) | 6 | 2.6 | 10 | 4.0 |
Abbreviations: AE, adverse event; BV, bevacizumab; CHF, congestive heart failure; GC, gemcitabine plus carboplatin; LV, left ventricular; PL, placebo; RPLS, reversible posterior leukoencephalopathy syndrome.
Safety population. All safety analyses were based on the primary safety patient population, which was defined as all patients who received any partial or full dose of protocol treatment (G, C, BV, or PL). Only treatment-emergent AEs (ie, within 30 days after last dose of protocol treatment) were included in the safety analyses.
Five patients randomly assigned to the GC + PL arm received one or two doses of BV in error and were assigned to the GC + BV arm for all safety analyses. Four patients randomly assigned to the GC + PL arm did not receive any protocol treatment and thus were not included in the safety analyses.
Five patients randomly assigned to the GC + PL arm received one or two doses of BV in error and were assigned to the GC + BV arm for all safety analyses.
Includes all fistula/abscess events: anal fistula, female genital tract fistula, pelvic abscess, perirectal abscess, rectal abscess.
Two (0.8%) were cases of RPLS confirmed by magnetic resonance imaging.