Resultsof a phase III, randomized, double-blind, placebocontrolledtrialofpegfilgrastim (PEG) inpatients (pts) receivingfirst-line FOLFOX or FOLFIRI andbevacizumab (B) forcolorectalcancer (CRC)

Abstract

Background: Theliteraturereportsthataddingbiologicstochemotherapy (ctx) mayincreasetheincidenceofclinicallysignificantneutropenia. histrialwasconductedtoevaluatetheefficacyof PEG inreducingtheincidenceoffebrileneutropenia (FN) inptswithlocally-advanced (LA) ormetastatic (m)CRC receivingfirst-linetreatmentwitheither FOLFOX/B or FOLFIRI/B. Methods: Keyeligibility: 18 yearsold; measurable, nonresectable CRC per RECIST 1.1. Ptswererandomlyassigned 1:1 toeitherplaceboor 6 mg PEG ~24 h afterctx/B. Thestudytreatmentperiodincludedfour Q2W cycles, butptscouldcontinuetheirassignedregimenuntilprogression. Ptswerestratifiedbyregion (NorthAmericavsrestofworld), stage (LA vsmCRC), andctx (FOLFOX vs FOLFIRI). Estimatedsamplesize (N = 800) wasbasedontheexpectedincidenceofgrade 3/4 FN (primaryendpoint) acrossthefirst 4 cyclesofctx/B, poweredfor PEG superiorityoverplacebo. Otherendpointsincludedoverallresponserate (ORR), progression-freesurvival (PFS), andoverallsurvival (OS). Results: 845 ptswererandomized (Nov 2009 toJan 2012) andreceivedstudytreatment; 783 ptscompleted 4 cyclesofctx/B. Medianagewas 61 years; 512 (61%) ptsweremale; 819 (97%) hadmCRC; 414 (49%) received FOLFOX, and 431 (51%) received FOLFIRI. Grade 3/4 FN (first 4 cycles) forplacebovs PEG was 5.7% vs 2.4%; OR 0.41; p = 0.014. A similarincidenceofother grade 3 adverseeventswasseeninbotharms (28% placebo; 27% PEG). Seetableforadditionalresults. Conclusions:PEGsignificantlyreducedtheincidenceofgrade 3/4 FN inthisptpopulationreceivingstandardctx/B for CRC. Follow-upisongoing.