Phase III Trial of Cetuximab With Continuous or Intermittent Fluorouracil, Leucovorin, and Oxaliplatin (Nordic FLOX) Versus FLOX Alone in First-Line Treatment of Metastatic Colorectal Cancer: The NORDIC-VII Study
Randomized trial shows adding cetuximab to FLOX does not improve survival in metastatic colorectal cancer, indicating limited efficacy with this regimen.
Key Points
To evaluate the efficacy and safety of adding cetuximab, given continuously or intermittently, to first-line Nordic FLOX chemotherapy in metastatic colorectal cancer according to KRAS and BRAF status.
Multicenter phase III randomized trial of 571 patients (566 evaluable in intention-to-treat analysis) with previously untreated metastatic colorectal cancer.
Patients were randomized to standard Nordic FLOX alone (arm A), cetuximab plus continuous FLOX (arm B), or cetuximab plus intermittent FLOX (arm C).
Tumor tissue was analyzed for KRAS mutations (n=498, 88%) and BRAF mutations (n=457, 81%) to assess treatment interaction and prognostic value.
Median progression-free survival did not significantly differ across arms: 7.9 months in arm A, 8.3 months in arm B, and 7.3 months in arm C.
Overall survival was 20.4 months in arm A, 19.7 months in arm B, and 20.3 months in arm C, with confirmed response rates of 41%, 49%, and 47%, respectively.
Cetuximab provided no additional benefit in KRAS wild-type tumors, while BRAF mutations (present in 12% of tested tumors) served as a strong negative prognostic marker.