osterior Leukoencephalopathy Syndrome (RPLS) [see Warnings and Precautions (5.10)]
Clinical Trial Experience
Because clinical trials are conducted under varying designs and in different patient populations, the adverse reaction rates reported in one clinical trial may not be easily compared to those rates reported in another clinical trial, and may not reflect the rates actually observed in clinical practice.
The safety of Zaltrap in combination with FOLFIRI was eva luated in 1216 previously treated patients with metastatic colorectal cancer (Study 1) who were treated with Zaltrap 4 mg per kg intravenous (N=611) or placebo (N=605) every two weeks (one cycle) in a randomized (1:1), double-blind, placebo-controlled Phase 3 study. Patients received a median of 9 cycles of Zaltrap/FOLFIRI or 8 cycles of placebo/FOLFIRI.
The most common adverse reactions (all grades, ≥20% incidence) reported at a higher incidence (2% or greater between-arm difference) in the Zaltrap/FOLFIRI arm , in order of decreasing frequency, were leukopenia, diarrhea, neutropenia, proteinuria, AST increased, stomatitis, fatigue, thrombocytopenia, ALT increased, hypertension, weight decreased, decreased appetite, epistaxis, abdominal pain, dysphonia, serum creatinine increased, and headache (see Table 1).
The most common Grade 3–4 adverse reactions (≥5%) reported at a higher incidence (2% or greater between-arm difference) in the Zaltrap/FOLFIRI arm, in order of decreasing frequency, were neutropenia, diarrhea, hypertension, leukopenia, stomatitis, fatigue, proteinuria, and asthenia (see Table 1).
The most frequent adverse reactions leading to permanent discontinuation in ≥1% of patients treated with Zaltrap/FOLFIRI regimen were asthenia/fatigue, infections, diarrhea, dehydration, hypertension, stomatitis, venous thromboembolic events, neutropenia, and proteinuria.
The Zaltrap dose was reduced and/or omitted in 17% of patients compared to placebo-dose modification in 5% of patients. Cycle delays >7 days occurred in 60% of patients treated with Zaltrap/FOLFIRI compared with 43% of patients treated with placebo/FOLFIRI.
The most common adverse reactions and laboratory abnormalities during study treatment in Study 1 where the incidence was ≥5% (all grades) in patients receiving Zaltrap in combination with FOLFIRI and which occurred at ≥2% higher frequency in patients treated with Zaltrap/FOLFIRI compared to placebo/FOLFIRI are shown in Table 1.
Table 1 – Selected Adverse Reactions and Laboratory Findings in Study 1: Primary System Organ Class
Preferred Term (%) Placebo/FOLFIRI
(N=605) Zaltrap/FOLFIRI
(N=611)
All grades Grades 3–4 All grades Grades 3–4
Note: Adverse Reactions are reported using MedDRA version MEDDRA13.1 and graded using NCI CTC version 3.0
*
Compilation of clinical and laboratory data
Infections and infestations
Urinary Tract Infection 6% 0.8% 9% 0.8%
Blood and lymphatic system disorders
Leukopenia 72% 12% 78% 16%
Neutropenia 57% 30% 67% 37%
Thrombocytopenia 35% 2% 48% 3%
Metabolism and nutrition disorders
Decreased Appetite 24% 2% 32% 3%
Dehydration 3% 1% 9% 4%
Nervous system disorders
Headache 9% 0.3% 22% 2%
Vascular disorders
