Abstract
BackgroundCetuximab, in combination with platinum chemotherapy plus 5-fluoruracil (5-FU), is approved for the first-line treatment of recurrent/metastatic squamous cell carcinoma of the head and neck (SCCHN). Cetuximab manufactured by ImClone (US commercial cetuximab) potentially results in higher systemic exposures than cetuximab manufactured by Boehringer Ingelheim (BI-manufactured cetuximab). This prospective, randomized, double-blind study compared the safety profiles of the two cetuximab formulations.MethodsPatients with previously untreated locoregionally recurrent and/or metastatic SCCHN were randomly assigned to receive the same dose of US commercial cetuximab (Arm A) or BI-manufactured cetuximab (Arm B), each in combination with cisplatin or carboplatin plus 5-FU. The primary outcome was all-grade, all-cause treatment-emergent adverse events (TEAEs).ResultsThe majority of patients experienced ≥1 TEAE, regardless of causality (Arm A: 75/77 patients, 97.4 %; Arm B: 68/71 patients, 95.8 %). TEAEs with the highest incidence included nausea, fatigue, and hypomagnesemia in both arms. The absolute risk difference between the two arms for patients experiencing at least one adverse event (AE) was 0.029 (p = 0.281, 95 % confidence interval [CI]: -0.024, 0.082) for AEs regardless of causality and 0.005 (p = 0.915, 95 % CI: -0.092, 0.103) for AEs possibly related to study drug. There were no significant differences between the two arms in the incidence of acneiform rash, cardiac events, infusion reactions, or hypomagnesemia. Overall survival, progression-free survival, and overall response rates were similar in the two arms.ConclusionsThere were no clinically meaningful differences in safety between US commercial cetuximab and BI-manufactured cetuximab in combination with platinum-based therapy with 5-FU in patients with locoregionally recurrent and/or metastatic SCCHN. The use of US commercial cetuximab in this combination chemotherapy regimen did not result in any unexpected safety signals. The efficacy results of this study are consistent with the efficacy results of the cetuximab arm of the EXTREME study.Trial registrationClinicalTrials.gov NCT01081041; date of registration: March 3, 2010).
Highlights
Cetuximab, in combination with platinum chemotherapy plus 5-fluoruracil (5-FU), is approved for the first-line treatment of recurrent/metastatic squamous cell carcinoma of the head and neck (SCCHN)
Patients were excluded from the study if they had: previous systemic chemotherapy, unless required as part of multimodal treatment for locally advanced head and neck cancer that was completed more than 4 months before study entry; previous treatment with monoclonal antibody therapy, other signal transduction inhibitors, or epidermal growth factor receptor (EGFR) targeting therapy, except for previous cetuximab treatment given as part of a multimodal treatment for locally advanced head and neck cancer that was completed more than 4 months before study entry; nasopharyngeal carcinoma; or other concomitant anticancer therapies
81 patients were randomly assigned to United States (US) commercial cetuximab plus chemotherapy (Arm A) and 73 patients were randomly assigned to Boehringer Ingelheim (BI)-manufactured cetuximab plus chemotherapy (Arm B) in the two-arm, randomized, double-blind phase of the study (Fig. 1)
Summary
In combination with platinum chemotherapy plus 5-fluoruracil (5-FU), is approved for the first-line treatment of recurrent/metastatic squamous cell carcinoma of the head and neck (SCCHN). Cetuximab manufactured by ImClone (US commercial cetuximab) potentially results in higher systemic exposures than cetuximab manufactured by Boehringer Ingelheim (BI-manufactured cetuximab) This prospective, randomized, double-blind study compared the safety profiles of the two cetuximab formulations. The standard of care (category 1 evidence) for recurrent/ metastatic SCCHN is the regimen used in the EXTREME study (Erbitux in First-Line Treatment of Recurrent or Metastatic Head and Neck Cancer), consisting of cetuximab in combination with cisplatin or carboplatin plus 5fluorouracil (5-FU) [2, 3]. In the EXTREME study, conducted in 17 European countries, 442 patients with previously untreated recurrent/metastatic SCCHN were randomized to receive chemotherapy alone (cisplatin or carboplatin plus 5-FU) or in combination with cetuximab [3]. Based on the results of the EXTREME study, cetuximab was approved by the European Union (EU) for the treatment of patients with SCCHN in combination with platinum-based chemotherapy for recurrent and/or metastatic disease [6], and later by the United States (US) Food and Drug Administration (FDA) for the first-line treatment of patients with recurrent locoregional disease or metastatic SCCHN in combination with platinum-based therapy with 5-FU [5]
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