Systematic Review on Infusion Reactions Associated with Chemotherapies and Monoclonal Antibodies for Metastatic Colorectal Cancer

Abstract

Objective: The objective of this systematic review is to summarize the literature to date on the rates of infusion reactions (IR) associated with chemotherapies and monoclonal antibody (mAb) drug therapies used for the treatment of metastatic colorectal cancer (mCRC) and the associated clinical and economic impact. Methods: This study searched Medline, Medline (R) In-Process, Embase and Cochrane Library databases for studies on IRs associated with chemotherapy and mAbs in mCRC patients from 2000-2011.Results: For chemotherapy, the incidence of IRs ranged from 0-71% for all grades and 0-15% for grade 3-4. Rates of all grade IRs associated with cetuximab ranged from 7.6-33% and grade 3-4 IR rates were 0-22%. Rates of all grade IRs associated with panitumumab ranged from 0-4% and rates of grade 3-4 IRs ranged from 0-1%. The overall rate of IRs associated with bevacizumab ranged from 1.6-11%, with a rate of 0-4% for grade 3-4 IRs. A range of 50-100% of patients with grade 3-4 IRs terminated chemotherapy, and 34-100% of cetuximab patients with grade 3-4 IRs discontinued cetuximab therapy. No data were reported for bevacizumab or panitumumab. Only one study evaluated the economic impact of IRs. The study compared cetuximab administrations without an IR to those with an IR requiring resource utilization and found that mean costs were $9308 and $1725 higher for those with an IR requiring an emergency room visit or hospitalization and for those with an IR requiring outpatient treatment, respectively. Conclusions: The incidence of IRs varies among different mAbs; and IRs may cause treatment disruption and require costly medical interventions.

The incidence of infusion reactions associated with monoclonal antibody drugs targeting the epidermal growth factor receptor in metastatic colorectal cancer patients: A systematic literature review and meta‐analysis of patient and study characteristics

“…The results of this study updated and expanded upon the 2012 systematic literature review by Song et al Although narrative in nature, their review reported incidences for cetuximab ranging from 7.6%‐33% in clinical trials and 27%‐32% in observational studies. We observed IR incidences for cetuximab ranging from 0%‐33% in clinical trials and 0.65%‐32% in observational studies.…”

“…IR in response to anti‐EGFR mAb drugs generally occur far less frequently than other therapies, although the reported range of incidence is wide (0%‐33%) . These proportions have been reported to vary by drug, as the incidence of IR associated with cetuximab ranged from 7.6%‐33%, whereas the proportions associated with panitumumab ranged from 0%‐4% . The cetuximab label reports IR incidence as occurring in approximately 3% of patients, and the panitumumab label reports an incidence of approximately 1%…”

Premedication and Chemotherapy Agents do not Impair Imgatuzumab (GA201)-Mediated Antibody-Dependent Cellular Cytotoxicity and Combination Therapies Enhance Efficacy

“…IRRs were observed in 76% of patients following the first infusion of single-agent imgatuzumab in a dose-escalation trial and have been reported with 7.6% to 33% of cetuximab infusions (4,7). As a fully human antibody, the incidence of infusion reactions with panitumumab is much lower (0%-4%; ref.…”

“…As a fully human antibody, the incidence of infusion reactions with panitumumab is much lower (0%-4%; ref. 7). Premedication with corticosteroids and/or antihistamines is mandated for the first infusion of cetuximab and recommended for subsequent cycles (8); similar recommendations are made for rituximab, alemtuzumab, and infliximab (9)(10)(11).…”

Controversies in antiepidermal growth factor receptor therapy in metastatic colorectal cancer

“…3,4 Unlike cetuximab, panitumumab does not mediate antibody-dependent cellular cytotoxicity and less often results in infusion reactions and anaphylactic reactions than cetuximab, because panitumumab is a fully humanized antibody. 5 Multiple in vitro, in vivo, and clinical trials have demonstrated that the efficacy of anti-EGFR monoclonal antibodies depends on lack of v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation, 6 although recent clinical and laboratory observations may challenge the current knowledge and clinical implications of KRAS mutation and anti-EGFR efficacy. [7][8][9] These anti-EGFR monoclonal antibodies have been evaluated in patients with advanced CRC as first-line, second-line, or later lines of therapy and as either a single agent or in combined chemotherapy.…”