Assessment of cetuximab-induced infusion reactions and administration rechallenge at an academic medical center

Abstract

Cetuximab is approved for treatment of squamous cell carcinoma of the head and neck (SCCHN). Cetuximab is generally well tolerated, but does carry a black box warning for infusion reactions (IRs). Incidence of IR in clinical trials was 15-20% for all grades and 3-5% for grades III-IV. Retrospective studies reported a higher incidence of all grade IRs and grades III-IV IR in areas of the Southeastern United States. Information regarding rechallenge doses after an IR has not been well described. At our institution, we frequently rechallenge on the same day after an initial IR. The primary objective was to determine the incidence, timing, IR grade, and completion of a rechallenge dose in patients who experienced an initial IR. Secondary objectives included: (1) determining the incidence and grade of IR in patients who received a first dose of cetuximab and (2) identifying specific risk factors for cetuximab IR with the first dose. A single-center retrospective chart review was conducted in SCCHN patients treated with cetuximab between June 2008 and September 2015 at the University of Kansas Hospital Cancer Center and inpatient setting. The majority of patients (87.9%) were able to be quickly and successfully rechallenged after an initial IR. Minimal patients (27.6%) experienced a rechallenge IR, resulting in only 1 patient discontinuation. Rechallenge doses were most frequently (37.9%) administered between 30 and 59 min after initial dose discontinuation. This was a single-center retrospective study based on data collected from electronic medical records. Other limitations include interpretation of infusion reactions on a subjective basis by providers. These findings demonstrate the practice of same-day rechallenges in initial IR patients is feasible and safe.

Incidence and associated factors of cetuximab-induced hypersensitivity infusion reactions in 1392 cancer patients treated in four French areas: a possible association with Lyme disease?

“…Management of CI-IRs is well described in the cetuximab SPC whatever the grade [ 1 ]. However, the present study is in line with previous ones that reported heterogeneous therapeutic management after low-grade (grade 1 and 2) infusion reactions [ 9 , 26 , 52 , 53 ]. This might result from the difficulty to detect and input subtle symptoms that occur during low-grade CI-IRs.…”

“…This might result from the difficulty to detect and input subtle symptoms that occur during low-grade CI-IRs. Some studies have found that the practice of cetuximab rechallenges in low-grade CI-IRs was feasible and safe [ 24 , 53 ]. Indeed, among the 34 patients who were rechallenged in our study, all experienced low-grade infusion reactions and only one re-challenged patient developed a subsequent reaction.…”

High incidence of cetuximab-related infusion reactions in head and neck patients

“… 12 A robust retrospective study of 243 patients showed an overall risk of CI-IR (grades 1–4) of 19.3% whose 6.6% with a high grade CI-IR.13 However, in a recent retrospective study, global CI-IR rate was among 20%. 13 This rate can be explained by the demographic region with a risk of high tick bites and therefore cross allergy with cetuximab, that is not the case in our study because we are in urban area.…”

“…In fact, it was showed that additional premedication like albuterol, famotidine and corticosteroids decreases high grade CI-IRs. 13 …”

“…Patients with grade 3 CI-IR were not rechallenged with cetuximab because of poor data available with this grade. 13 …”