Table 3.
Summary of the incidence and relative risk of adverse events across the six completed phase III ramucirumab clinical trials
| HTN, n (%) |
Proteinuria, n (%) |
Bleeding, n (%) |
GI bleeding, n (%) |
|||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Safety population | All grade | Grade ≥ 3 | All grade | Grade ≥ 3 | All grade | Grade ≥ 3 | All grade | Grade ≥ 3 | ||
| RAM | N = 2748 | 585 (21.3) | 246 (9.0) | 259 (9.4) | 31 (1.1) | 1031 (37.5) | 74 (2.7) | 186 (6.8) | 45 (1.6) | |
| Control | N = 2248 | 167 (7.4) | 57 (2.5) | 70 (3.1) | 1 (0.04)a | 426 (19.0) | 62 (2.8) | 103 (4.6) | 36 (1.6) | |
| Relative risk (95% CI) | 2.7 (2.3–3.2) | 3.7 (2.8–4.9) | 3.4 (2.6–4.3) | 8.3 (2.9–24.1) | 2.0 (1.8–2.2) | 1.1 (0.8–1.5) | 1.6 (1.3–2.0) | 1.1 (0.7–1.7) | ||
| GI perforation, n (%) | ATE, n (%) | VTEb, n (%) | IRR, n (%) | Wound-healing complications, n (%) | ||||||
| All grade | Grade ≥ 3 | All grade | Grade ≥ 3 | All grade | Grade ≥ 3 | All gradeb | Grade ≥ 3 | All grade | Grade ≥ 3 | |
| RAM | 30 (1.1) | 28 (1.0) | 38 (1.4) | 21 (0.8) | 106 (3.9) | 56 (2.0) | 180 (6.6) | 28 (1.0) | 14 (0.5) | 5 (0.2) |
| Control | 7 (0.3) | 6 (0.3) | 40 (1.8) | 19 (0.8) | 116 (5.2) | 61 (2.7) | 104 (4.6) | 13 (0.6) | 4 (0.2) | 0 (0)a |
| Relative risk (95% CI) | 3.2 (1.5–7.0) | 3.2 (1.4–7.3) | 0.8 (0.5–1.3) | 0.9 (0.5–1.7) | 0.7 (0.5–1.1) | 0.7 (0.4–1.2) | 1.4 (0.8–2.3) | 1.5 (0.8–2.7) | 2.0 (0.8–5.1) | 1.9 (0.5–7.5) |
a
For rare events (events that were not observed in at least one treatment arm in any study), the relative risk might not be reliable due to large variability.
b
Random-effects analysis model utilized due to significant identified heterogeneity.
ATE, arterial thromboembolic events; CI, confidence interval; GI, gastrointestinal; HTN, hypertension; IRR, infusion-related reactions; RAM, ramucirumab; VTE, venous thromboembolic events.