Table 2.
Summary of infusion rates for patients with or without immediate infusion-related reactions (narrow termsa) by study and overall in ramucirumab-treated patients
| Study | Infusion rate, mg/min | |||
|---|---|---|---|---|
| Pts with ≥ 1 IRR | Pts with no IRR | |||
|
REGARD [21] |
N | 5 | 224 | |
| Mean (SD) | 9.8 (2.69) | 8.5 (2.64) | ||
| Median (IQR) | 9.2 (8.1–12.1) | 8.4 (6.9–9.6) | ||
| Min–Max | 6.6–13.1 | 2.4–32.5 | ||
|
RAINBOWb [22] |
N | 45 | 279 | |
| Mean (SD) | 7.5 (1.89) | 8.4 (2.15) | ||
| Median (IQR) | 7.6 (6.7–8.5) | 8.0 (6.9–9.6) | ||
| Min–Max | 3.0–13.2 | 4.3–17.9 | ||
|
REVELb [23] |
N | 51 | 574 | |
| Mean (SD) | 16.2 (25.90) | 12.6 (7.72) | ||
| Median (IQR) | 12.0 (9.4–13.2) | 12.0 (10.3–13.9) | ||
| Min–Max | 0.5–190.0 | 3.5–182.0 | ||
|
RAISEb [24] |
N | 45 | 481 | |
| Mean (SD) | 9.5 (4.84) | 9.5 (2.33) | ||
| Median (IQR) | 8.8 (7.3–10.7) | 9.1 (7.7–10.9) | ||
| Min–Max | 3.1–36.0 | 4.0–19.9 | ||
|
REACH [25] |
N | 41 | 275 | |
| Mean (SD) | 8.3 (2.09) | 8.9 (1.95) | ||
| Median (IQR) | 8.3 (7.4–9.2) | 8.5 (7.5–10.0) | ||
| Min–Max | 3.2–13.0 | 3.2–15.3 | ||
|
REACH-2 [26] |
N | 17 | 179 | |
| Mean (SD) | 7.1 (2.90) | 8.6 (2.09) | ||
| Median (IQR) | 7.1 (5.7–8.4) | 8.4 (7.2–9.7) | ||
| Min–Max | 1.0–11.9 | 3.2–17.0 | ||
|
RAINFALLb [27] |
N | 15 | 306 | |
| Mean (SD) | 10.4 (3.04) | 8.8 (2.27) | ||
| Median (IQR) | 9.7 (7.5–13.9) | 8.6 (6.9–10.3) | ||
| Min–Max | 6.7–15.0 | 4.3–18.0 | ||
|
RANGEb [28] |
N | 18 | 237 | |
| Mean (SD) | 11.0 (3.42) | 11.9 (2.84) | ||
| Median (IQR) | 11.2 (9.6–12.9) | 11.8 (10.0–13.7) | ||
| Min–Max | 3.3–16.0 | 5.3–23.2 | ||
|
(I4T-MC-JVDB) |
N | 4 | 156 | |
| Mean (SD) | 4.8 (1.48) | 9.5 (3.30) | ||
| Median (IQR) | 4.7 (3.6–6.1) | 8.4 (7.1–11.4) | ||
| Min–Max | 3.4–6.4 | 4.0–19.5 | ||
|
(I4T-MC-JVCZ) |
N | 11 | 230 | |
| Mean (SD) | 11.1 (5.09) | 11.1 (3.30) | ||
| Median (IQR) | 12.1 (7.3–16.0) | 10.6 (8.7–13.0) | ||
| Min–Max | 2.5–18.6 | 4.6–25.0 | ||
| All studiesc | N | 252 | 2941 | |
| Mean (SD) | 10.3 (12.35) | 10.1 (4.39) | ||
| Median (IQR) | 8.7 (7.3–11.4) | 9.6 (7.9–11.7) | ||
| Min–Max | 0.5–190.0 | 2.4–182.0 | ||
Infusion rates were calculated as total dose/duration of infusion on day of earliest IRR event for patients with at least one immediate IRR and as total dose/infusion time on the first ramucirumab dose for patients with no IRR events
Two outliers of infusion data (one with infusion rate = 182 mg/min calculated from 910 mg total dose infused within 5 min; one with infusion rate = 190 mg/min calculated from 950 mg total dose infused within 5 min; both in REVEAL) were considered due to data entry issues
CAP capecitabine, CIS cisplatin, DOC docetaxel, FOLFIRI irinotecan, folinic acid, and 5FU, IQR interquartile range, IRR infusion-related reaction, Max maximum, Min minimum, N total number of patients, PAC paclitaxel, pts patients, Q quartile, RAM ramucirumab, SD standard deviation, 5FU 5-fluorouracil
aBroad- and narrow-scope preferred terms were used within the Standardized Medical Dictionary for Regulatory Activities (MedDRA) queries. “Narrow” preferred terms included terms that are highly likely to represent the condition of interest and were considered sufficient to identify immediate IRRs with reasonable precision and to appropriately reflect the incidence rate of immediate IRRs
bStudies in combination with chemotherapy (RAINBOW: RAM + PAC; REVEL: RAM + DOC; RAISE: RAM + FOLFIRI; RAINFALL: RAM + CAP [or 5FU] + CIS; RANGE: RAM + DOC; Study JVCZ: RAM + PAC)
cInfusion times were missing for 23 patients across the studies