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3523 Background: Phase III trials show inconsistent effects when anti-EGFR drugs are added to cytotoxic therapy in aCRC. Benefits, when present, are confined to patients (pts) determined retrospectively to have KRAS wild-type (wt) tumours. PICCOLO is a multicentre randomized controlled trial, amended in June 2008 to include prospective KRAS testing, to evaluate the addition of panitumumab (Pan) to single-agent irinotecan (Ir) as second- or subsequent-line therapy for KRAS-wt aCRC. METHODS: Eligible pts had: measurable aCRC progressing during/after ≥1 prior regimen with fluoropyrimidines ± other drugs; no prior Ir; WHO PS 0-2. Until June '08, pts were allocated 1:1:1 to Ir, IrPan or Ir/ciclosporin, with retrospective KRAS analysis. Thereafter, KRAS was tested prospectively (by pyrosequencing of c.12-13 and 61) and pts with KRAS-wt were allocated 1:1 to Ir (Ir 350 mg/m(2) [300 mg/m(2) if ≥70 yrs or PS2], q3w) or IrPan (same Ir plus Pan 9 mg/kg, q3w). Primary analysis is ITT overall survival (OS) in KRAS-wt pts not pretreated with anti-EGFR therapy (80% power, HR 0.70, α=0.05, 2-sided). Secondary endpoints include % progression-free at 12 wks, PFS, RR, toxicity and QL. Planned molecular subgroups include BRAF, NRAS, KRAS c.146 and PIK3CA. RESULTS: 460 KRAS-wt pts were recruited to the primary analysis (324 after June '08, KRAS-tested prospectively); median age 63 yrs; 94% PS0-1; 95% had received prior oxaliplatin. With 312 events and median follow-up of survivors 10.2 mo, OS was not improved: median IrPan = 10.4 mo, Ir = 10.5 mo, HR 0.91 (95%CI [0.73, 1.14], p=0.44), but trended towards improved survival after 12 mo. Planned subgroup analysis shows worse survival, and disbenefit with Pan in BRAF-mut pts (n=63, HR=1.87, [95%CI 1.07, 3.27]); conversely, KRAS/BRAF-wt pts show a stronger but still non-significant trend towards benefit (n=348, HR=0.86 [0.66, 1.11]). CONCLUSIONS: PICCOLO did not meet its primary endpoint of improved OS with panitumumab in KRAS-wt aCRC, but a trend was seen towards survival benefit after 12 months, especially in KRAS/BRAF-wt pts. Conversely, pts with BRAF-mut tumours had significant disbenefit with Pan. Full results, including PFS and planned molecular subgroups, will be presented.


Journal article


J Clin Oncol

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