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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.

Tveit, Kjell Magne; Guren, Tormod; Glimelius, Bengt; Pfeiffer, Per; Sorbye, Halfdan; Pyrhonen, Seppo; Sigurdsson, Fridbjorn; Kure, Elin; Ikdahl, Tone and Skovlund, Eva, et al. (2012) In Journal of Clinical Oncology 30(15). p.1755-1762
Abstract
PURPOSEThe NORDIC-VII multicenter phase III trial investigated the efficacy of cetuximab when added to bolus fluorouracil/folinic acid and oxaliplatin (Nordic FLOX), administered continuously or intermittently, in previously untreated metastatic colorectal cancer (mCRC). The influence of KRAS mutation status on treatment outcome was also investigated. PATIENTS AND METHODSPatients were randomly assigned to receive either standard Nordic FLOX (arm A), cetuximab and FLOX (arm B), or cetuximab combined with intermittent FLOX (arm C). Primary end point was progression-free survival (PFS). Overall survival (OS), response rate, R0 resection rate, and safety were secondary end points.ResultsOf the 571 patients randomly assigned, 566 were evaluable... (More)
PURPOSEThe NORDIC-VII multicenter phase III trial investigated the efficacy of cetuximab when added to bolus fluorouracil/folinic acid and oxaliplatin (Nordic FLOX), administered continuously or intermittently, in previously untreated metastatic colorectal cancer (mCRC). The influence of KRAS mutation status on treatment outcome was also investigated. PATIENTS AND METHODSPatients were randomly assigned to receive either standard Nordic FLOX (arm A), cetuximab and FLOX (arm B), or cetuximab combined with intermittent FLOX (arm C). Primary end point was progression-free survival (PFS). Overall survival (OS), response rate, R0 resection rate, and safety were secondary end points.ResultsOf the 571 patients randomly assigned, 566 were evaluable in intention-to-treat (ITT) analyses. KRAS and BRAF mutation analyses were obtained in 498 (88%) and 457 patients (81%), respectively. KRAS mutations were present in 39% of the tumors; 12% of tumors had BRAF mutations. The presence of BRAF mutations was a strong negative prognostic factor. In the ITT population, median PFS was 7.9, 8.3, and 7.3 months for the three arms, respectively (not significantly different). OS was almost identical for the three groups (20.4, 19.7, 20.3 months, respectively), and confirmed response rates were 41%, 49%, and 47%, respectively. In patients with KRAS wild-type tumors, cetuximab did not provide any additional benefit compared with FLOX alone. In patients with KRAS mutations, no significant difference was detected, although a trend toward improved PFS was observed in arm B. The regimens were well tolerated. CONCLUSIONCetuximab did not add significant benefit to the Nordic FLOX regimen in first-line treatment of mCRC. (Less)
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Journal of Clinical Oncology
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30
issue
15
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1755 - 1762
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American Society of Clinical Oncology
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  • wos:000304427600008
  • pmid:22473155
  • scopus:84861432557
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1527-7755
DOI
10.1200/JCO.2011.38.0915
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English
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@article{911e0e99-e8b2-4963-95df-b386a70c42a7,
  abstract     = {PURPOSEThe NORDIC-VII multicenter phase III trial investigated the efficacy of cetuximab when added to bolus fluorouracil/folinic acid and oxaliplatin (Nordic FLOX), administered continuously or intermittently, in previously untreated metastatic colorectal cancer (mCRC). The influence of KRAS mutation status on treatment outcome was also investigated. PATIENTS AND METHODSPatients were randomly assigned to receive either standard Nordic FLOX (arm A), cetuximab and FLOX (arm B), or cetuximab combined with intermittent FLOX (arm C). Primary end point was progression-free survival (PFS). Overall survival (OS), response rate, R0 resection rate, and safety were secondary end points.ResultsOf the 571 patients randomly assigned, 566 were evaluable in intention-to-treat (ITT) analyses. KRAS and BRAF mutation analyses were obtained in 498 (88%) and 457 patients (81%), respectively. KRAS mutations were present in 39% of the tumors; 12% of tumors had BRAF mutations. The presence of BRAF mutations was a strong negative prognostic factor. In the ITT population, median PFS was 7.9, 8.3, and 7.3 months for the three arms, respectively (not significantly different). OS was almost identical for the three groups (20.4, 19.7, 20.3 months, respectively), and confirmed response rates were 41%, 49%, and 47%, respectively. In patients with KRAS wild-type tumors, cetuximab did not provide any additional benefit compared with FLOX alone. In patients with KRAS mutations, no significant difference was detected, although a trend toward improved PFS was observed in arm B. The regimens were well tolerated. CONCLUSIONCetuximab did not add significant benefit to the Nordic FLOX regimen in first-line treatment of mCRC.},
  author       = {Tveit, Kjell Magne and Guren, Tormod and Glimelius, Bengt and Pfeiffer, Per and Sorbye, Halfdan and Pyrhonen, Seppo and Sigurdsson, Fridbjorn and Kure, Elin and Ikdahl, Tone and Skovlund, Eva and Fokstuen, Tone and Hansen, Flemming and Hofsli, Eva and Birkemeyer, Elke and Johnsson, Anders and Starkhammar, Hans and Yilmaz, Mette Karen and Keldsen, Nina and Erdal, Anne Berit and Dajani, Olav and Dahl, Olav and Christoffersen, Thoralf},
  issn         = {1527-7755},
  language     = {eng},
  number       = {15},
  pages        = {1755--1762},
  publisher    = {American Society of Clinical Oncology},
  series       = {Journal of Clinical Oncology},
  title        = {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.},
  url          = {http://dx.doi.org/10.1200/JCO.2011.38.0915},
  volume       = {30},
  year         = {2012},
}