Lancet Oncol 2013; 14: 749–59 R2 김민제 / Prof. 백선경. Journal conference

 Panitumumab, Irinotcan and Ciclosporin in COLOrectal cancer (PICCOLO) trial : Irinotecan alone, irinotecan plus ciclosporin or irinotecan plus panitumumab[IrPan]  Therapeutic antibodies targeting EGFR  Randomised trial in Fluorouracil-resistant adanc ed colorectal cancer  In April 2008, KRAS mutation reported to be : Negative biomarker for EGFR targeted therapy

 Aim of trial was amended!! : Evaluation of panitumumab woud focus on patients with KRAS wild-type tumors  patients with KRAS mutations were allocated to irinotecan or irinotecan plus ciclosporin  In this journal…. : Final results of Irinotecan vs IrPan  for patients with KRAS wild type tumors  who had not received previous anti EGFR therapy

 Study design and Patients : Multicenter (60) in UK, randomised controlled “Aged 18yrs or older” “Histologcally confirmed Colorectal Ca.” “Inoperable advanced disease” “Progress after fluoropyrimidine containing chemotherapy” “RECIST mesurable disease” “WHO performance 0~2” “e.GFR >50 ml/min” “Hb > 10g/dL” “WBC > 3 × 10 ⁹ /L” “platelet >100 × 10 ⁹ /L” “Bilirubin < 25 μ mol/L”

 Randomisation and masking : Dec 4, 2006 ~ June 9, 2008  Equally allocated to ‘Irinotecan alone’ Irinotecan plus ciclosporin’ or ‘IrPan’ : June 10, 2008  Patients with unknown or mutated KRAS status were allocated to irinotecan or plus ciclosporin only : Sep 1, 2008 (New protocol)  Randomisation by KRAS status

 Procedures : IV infusion of Irinotecan 350mg/m2 every 3wk : Patients in IrPan also received IV infusion of panitumumab 9mg/kg every 3wk : Treatment continued until disease progression or unaccepable toxicity  after 12wks stable or responding could be offered planned break from irinotecan (RECIST response assessed every 12weeks)

 1. Adding panitumumab to irinotecan did not improve overall survival of patints with wild type KRAS tumors  2. Further refinement of molecular selection is needed for benefits derived form EGFR agents