Phase III Clinical Trial (RERISE study) Results of Efficacy and Safety of Radotinib Compared with Imatinib in Newly Diagnosed Chronic Phase Chronic Myeloid Leukemia

Clin Cancer Res. 2017 Dec 1;23(23):7180-7188. doi: 10.1158/1078-0432.CCR-17-0957. Epub 2017 Sep 22.

Abstract

Purpose: Radotinib is a second-generation BCR-ABL1 tyrosine kinase inhibitor (TKI) approved in Korea for chronic phase chronic myeloid leukemia (CML-CP) in patients newly diagnosed or with insufficient response to other TKIs. This study was conducted to evaluate the efficacy and safety of radotinib as first-line therapy for CML-CP.Experimental Design: This multinational, open-label study assigned patients (1:1:1) to one of two twice-daily radotinib doses, or imatinib daily. The primary endpoint was major molecular response (MMR) by 12 months.Results: Two hundred forty-one patients were randomized to receive radotinib 300 mg (n = 79) or 400 mg twice-daily (n = 81), or imatinib 400 mg daily (n = 81). MMR rates by 12 months were higher in patients receiving radotinib 300 mg (52%) or radotinib 400 mg twice-daily (46%) versus imatinib (30%; P = 0.0044 and P = 0.0342, respectively). Complete cytogenetic response (CCyR) rates by 12 months were higher for radotinib 300 mg (91%) versus imatinib (77%; P = 0.0120). Early molecular response at 3 months occurred in 86% and 87% of patients receiving radotinib 300 mg and radotinib 400 mg, respectively, and 71% of those receiving imatinib. By 12 months, no patients had progression to accelerated phase or blast crisis. Most adverse events were manageable with dose reduction.Conclusions: Radotinib demonstrated superiority over imatinib in CCyR and MMR in patients newly diagnosed with Philadelphia chromosome-positive CML-CP. This trial was registered at www.clinicaltrials.gov as NCT01511289 Clin Cancer Res; 23(23); 7180-8. ©2017 AACR.

Publication types

  • Clinical Trial, Phase III
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Benzamides / administration & dosage
  • Benzamides / adverse effects
  • Benzamides / therapeutic use*
  • Drug Administration Schedule
  • Female
  • Fusion Proteins, bcr-abl / genetics
  • Humans
  • Imatinib Mesylate / administration & dosage
  • Imatinib Mesylate / adverse effects
  • Imatinib Mesylate / therapeutic use*
  • Leukemia, Myeloid, Chronic-Phase / drug therapy*
  • Leukemia, Myeloid, Chronic-Phase / genetics
  • Male
  • Middle Aged
  • Neutropenia / chemically induced
  • Protein Kinase Inhibitors / adverse effects
  • Protein Kinase Inhibitors / therapeutic use
  • Pyrazines / administration & dosage
  • Pyrazines / adverse effects
  • Pyrazines / therapeutic use*
  • Remission Induction
  • Thrombocytopenia / chemically induced
  • Treatment Outcome

Substances

  • 4-methyl-N-(3-(4-methylimidazol-1-yl)-5-trifluoromethylphenyl)-3-(4-pyrazin-2-ylpyrimidin-2-ylamino)benzamide
  • Benzamides
  • Protein Kinase Inhibitors
  • Pyrazines
  • Imatinib Mesylate
  • Fusion Proteins, bcr-abl

Associated data

  • ClinicalTrials.gov/NCT01511289