Cetuximab plus platinum-based chemotherapy in head and neck squamous cell carcinoma: a randomized, double-blind safety study comparing cetuximab produced from two manufacturing processes using the EXTREME study regimen

BMC Cancer

Research Article

Denis Soulières¹  Coleman K. Obasaju²  Steve Chin²  Katherine Bryant²  Shao-Chun Chang²  Shuang He²  Hyun Jung Lee²  Jose Luis Aguilar³  Scott Ernst⁴  Krzysztof Misiukiewicz⁵  Eric Chen⁶  Douglas Adkins⁷ 

[1] Centre Hospitalier de l’Université de Montréal, Montréal, Québec, Canada;Eli Lilly and Company, Indianapolis, IN, USA;Instituto Nacional de Cancerologia, Mexico City, Mexico;London Regional Cancer Center, London, Ontario, Canada;Mount Sinai School of Medicine Tisch Cancer Institute, New York, NY, USA;Princess Margaret Hospital, Toronto, Ontario, Canada;Washington University School of Medicine, Box 8056, 660 S. Euclid, 63110, St. Louis, MO, USA;

关键词: Carcinoma, squamous cell;    Cetuximab;    Head and neck cancer;    Safety;   

DOI  :  10.1186/s12885-016-2064-0

 received in 2015-04-16, accepted in 2016-01-10,  发布年份 2016

来源: Springer

【 摘 要 】

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).

【 授权许可】

CC BY   
© Soulières et al. 2016