Weekly and every 2 weeks cetuximab maintenance therapy after platinum-based chemotherapy plus cetuximab as first-line treatment for non-small cell lung cancer: randomized non-comparative phase IIIb NEXT trial

• Published in: Targeted oncology Vol. 10; no. 2; pp. 255 - 265
• Main Authors: Heigener, David F., Pereira, José Rodrigues, Felip, Enriqueta, Mazal, Juraj, Manzyuk, Lyudmila, Tan, Eng Huat, Merimsky, Ofer, Sarholz, Barbara, Esser, Regina, Gatzemeier, Ulrich
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01-06-2015; Springer Nature B.V
• Subjects: Aged; Antineoplastic Combined Chemotherapy Protocols - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Biomedicine; Brazil; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - mortality; Carcinoma, Non-Small-Cell Lung - pathology; Cetuximab - administration & dosage; Cetuximab - adverse effects; Disease Progression; Disease-Free Survival; Drug Administration Schedule; Europe; Female; Humans; Israel; Kaplan-Meier Estimate; Lung Neoplasms - drug therapy; Lung Neoplasms - mortality; Lung Neoplasms - pathology; Maintenance Chemotherapy; Male; Medicine; Medicine & Public Health; Middle Aged; Oncology; Original Research; Singapore; Time Factors; Treatment Outcome; Brazil; Singapore; Israel; Europe; Chemotherapy; NSCLC; Cetuximab; Maintenance therapy; Every 2 weeks
• ISSN: 1776-2596; 1776-260X
• DOI: 10.1007/s11523-014-0336-7

The First-Line Erbitux in Lung Cancer (FLEX) trial showed that the addition of cetuximab to chemotherapy followed by weekly cetuximab maintenance significantly improved survival in the first-line treatment of advanced non-small cell lung cancer (NSCLC). The phase IIIb NSCLC Erbitux Trial (NEXT) trial (NCT00820755) investigated the efficacy and safety of weekly and every 2 weeks cetuximab maintenance therapy in this setting. Patients were treated with platinum-based chemotherapy plus cetuximab, and those progression-free after four to six cycles were randomized to every 2 weeks (500 mg/m
2
) or weekly (250 mg/m
2
) cetuximab maintenance. Randomization was stratified for tumor histology and response status. The primary endpoint for a regimen would be reached if the lower boundary of the 95 % confidence interval (CI) for the 1-year survival rate exceeded 55 %. A planned 480 patients were to be randomized. However, enrollment was curtailed following a negative opinion from the European Medicines Agency with regard to the use of cetuximab in this setting. After combination therapy, 311/583 (53.3 %) patients without progression were randomized to maintenance therapy: 157 to every 2 weeks cetuximab and 154 to weekly cetuximab. Baseline characteristics were balanced between these groups and exposure to cetuximab was similar. The 1-year survival rate was 62.8 % (95 % CI, 54.7–70.0) for every 2 weeks cetuximab and 64.4 % (95 % CI, 56.2–71.4) for weekly cetuximab. Safety profiles were similar, manageable, and in line with expectations. Therefore, in patients with advanced NSCLC who were progression-free after four to six cycles of first-line chemotherapy plus cetuximab, weekly and every 2 weeks cetuximab maintenance therapy were associated with similar survival outcomes.