NO USE OF SUTENT IN COLORECTAL CANCER 

J Clin Oncol. 2013 Jan 28. [Epub ahead of print]

Fluorouracil, Leucovorin, and Irinotecan Plus Either Sunitinib or Placebo in Metastatic Colorectal Cancer: A Randomized, Phase III Trial.

Carrato A, Swieboda-Sadlej A, Staszewska-Skurczynska M, Lim R, Roman L, Shparyk Y, Bondarenko I, Jonker DJ, Sun Y, De la Cruz JA, Williams JA,Korytowsky B, Christensen JG, Lin X, Tursi JM, Lechuga MJ, Van Cutsem E.

Source

Alfredo Carrato, Ramon y Cajal University Hospital, Madrid, Spain; Anna Swieboda-Sadlej and Marzanna Staszewska-Skurczynska, Samodzielny Publiczny Centralny Szpital Kliniczny, Warsaw, Poland; Robert Lim, National University Health System, National University of Singapore, Singapore; Laslo Roman, Leningrad Regional Oncology Centre, St. Petersburg, Russian Federation; Yaroslav Shparyk, Lviv State Oncologic Regional Treatment and Diagnostic Center, Lviv; Igor Bondarenko, City Multiple-Discipline Clinical Hospital #4, Dnipropetrovsk, Ukraine; Derek J. Jonker, The Ottawa Hospital Cancer Center, Ottawa, Ontario, Canada; Yan Sun, Cancer Institute and Hospital, Chinese Academy of Medical Sciences, Panjia Yuan, Bejing, China; Jhony A. De la Cruz, Grupo Oncológico Acapulco, Facultad de Medicina, Universidad Autónoma de Guerrero y Secretaría de Salud, Guerrero, Mexico; J. Andrew Williams, James G. Christensen, and Xun Lin, Pfizer Oncology, La Jolla, CA; Beata Korytowsky, Pfizer Oncology, New York, NY; Jennifer M. Tursi and Maria J. Lechuga, Pfizer Italia, Milan, Italy; and Eric Van Cutsem, University Hospital Gasthuisberg, Leuven, Belgium.

Abstract

PURPOSEThis double-blind, phase III study aimed to demonstrate that sunitinib plus FOLFIRI (fluorouracil, leucovorin, and irinotecan) was superior to placebo plus FOLFIRI in previously untreated metastatic colorectal cancer (mCRC). PATIENTS AND METHODSPatients were randomly assigned to receive FOLFIRI and either sunitinib (37.5 mg per day) or placebo (4 weeks on treatment, followed by 2 weeks off [schedule 4/2]) until disease progression. The primary end point was progression-free survival (PFS). Secondary end points included overall survival, safety, and patient-reported outcomes. The correlation between genotype and clinical outcomes was also analyzed.ResultsIn all, 768 patients were randomly assigned to sunitinib plus FOLFIRI (n = 386) or placebo plus FOLFIRI (n = 382). Following a second prespecified interim analysis, the study was stopped because of potential futility of sunitinib plus FOLFIRI. Final results are reported. The PFS hazard ratio was 1.095 (95% CI, 0.892 to 1.344; one-sided stratified log-rank P = .807), indicating a lack of superiority for sunitinib plus FOLFIRI. Median PFS for the sunitinib arm was 7.8 months (95% CI, 7.1 to 8.4 months) versus 8.4 months (95% CI, 7.6 to 9.2 months) for the placebo arm. Sunitinib plus FOLFIRI was associated with more grade ≥ 3 adverse events and laboratory abnormalities than placebo (especially diarrhea, stomatitis/oral syndromes, fatigue, hand-foot syndrome, neutropenia, thrombocytopenia, anemia, and febrile neutropenia). More deaths as a result of toxicity (12 v four) and significantly more dose delays, dose reductions, and treatment discontinuations occurred in the sunitinib arm. CONCLUSIONSunitinib 37.5 mg per day (schedule 4/2) plus FOLFIRI is not superior to FOLFIRI alone and has a poorer safety profile. This combination regimen is not recommended for previously untreated mCRC.