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Final results of CONFIRM 2: A multinational, randomized, double-blind, phase III study in 2nd line patients (pts) with metastatic colorectal cancer (mCRC) receiving FOLFOX4 and PTK787/ZK 222584 (PTK/ZK) or placebo
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2007
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PathologyPharmacotherapyPre-clinical PharmacologyAngiogenesisOncologyGastrointestinal OncologyMetronomic TherapyVegf ReceptorsClinical TrialsDiagnostic SciencesRadiation OncologyConfirm 2Cancer ResearchCancer GrowthHealth SciencesColorectal CancerMetastatic Colorectal CancerVascular BiologyCancer TreatmentPharmacologyPtk/zk ArmPoor PrognosisMedicinePhase Iii Study
4033 Background: PTK/ZK, a novel, oral, anti-angiogenic compound that inhibits all VEGF receptors has been investigated in two multinational randomized phase 3 studies in 1st (CONFIRM 1) and 2nd line (CONFIRM 2) mCRC. Interim analyses (IA) have been presented at ASCO 2005 and 2006, respectively. Methods: In CONFIRM 2, 855 pts were randomized to FOLFOX4 plus PTK/ZK (1250 mg, qd), or placebo. Eligibility included histologically documented mCRC, pre-treatment for metastatic disease with irinotecan-/fluoropyrimidine- based therapy, measurable disease by RECIST, PS of 0–2 and adequate organ function. Pts were stratified based on PS (0 vs. 1–2) and baseline serum Lactate Dehydrogenase (LDH = vs. >1.5 × ULN). The primary endpoint is overall survival (OS). Secondary endpoints included OS and PFS in high LDH pts (LDH > 1.5 × ULN). Results: At the time of IA in July 2005, OS was 12.1 mo in the PTK/ZK and 11.8 mo in the placebo arm (HR: 0.94; p=0.511). PFS was significantly longer in the PTK/ZK arm (5.5 mo vs. 4.1 mo; HR: 0.83; p=0.026). LDH, a marker for poor prognosis in mCRC, is predictive of the outcome in the PTK/ZK arm. When treated with PTK/ZK, high LDH pts showed a strong improvement in PFS (5.6 mo vs. 3.8 mo; HR: 0.63; p<0.001) and in OS (9.6 mo vs. 7.5 mo; HR: 0.78; p=0.10). Adverse events (AE) were similar to that of the CONFIRM 1 trial. Final analysis for OS, PFS and safety is planned for Feb. 2007 after 732 events (compared to 413 in the IA) and will be presented at the meeting. Conclusions: While the primary endpoint for OS was not met in the IA, PTK/ZK improves PFS significantly in the overall population, and shows strong activity (improved PFS and OS) in patients with high baseline serum LDH. Final results of the study will be presented at the meeting. No significant financial relationships to disclose.