Long-term outcome with dasatinib after imatinib failure in chronic-phase chronic myeloid leukemia: follow-up of a phase 3 study

Blood. 2014 Apr 10;123(15):2317-24. doi: 10.1182/blood-2013-10-532341. Epub 2014 Feb 25.

Abstract

We present long-term follow-up of a dasatinib phase 3 study of patients with imatinib-resistant/-intolerant chronic myeloid leukemia (CML). In the CA180-034 study, 670 patients with imatinib-resistant/-intolerant CML in chronic phase (CML-CP) received dasatinib 100 mg once daily, 50 mg twice daily, 140 mg once daily, or 70 mg twice daily. At 6 years, 188 (28%) of 670 patients remained on study treatment. Estimated 6-year protocol-defined progression-free survival (PFS) rates were 49%, 51%, 40%, and 47%, respectively, and estimated 6-year overall survival (OS) rates were 71%, 74%, 77%, and 70%, respectively (intent-to-treat population, including protocol-defined progression or death after discontinuation). Estimated 6-year rates of survival without transformation on study treatment were 76%, 80%, 83%, and 74%, respectively. Major molecular response was achieved in 43% (100 mg once daily) and 40% (all other arms) of patients by 6 years. Molecular and cytogenetic responses at 3 and 6 months were highly predictive of PFS and OS. Notably, estimated 6-year PFS rates based on ≤1%, >1% to 10%, and >10% BCR-ABL transcripts at 3 months were 68%, 58%, and 26%, respectively. Most adverse events occurred by 2 years. Imatinib-resistant/-intolerant patients with CML-CP can experience long-term benefit with dasatinib therapy, particularly if achieving BCR-ABL ≤10% at 3 months. This study was registered at ClinicalTrials.gov: NCT00123474.

Publication types

  • Clinical Trial, Phase III
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / therapeutic use*
  • Benzamides / therapeutic use
  • Dasatinib
  • Disease-Free Survival
  • Drug Resistance, Neoplasm
  • Follow-Up Studies
  • Fusion Proteins, bcr-abl / blood
  • Humans
  • Imatinib Mesylate
  • Kaplan-Meier Estimate
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy*
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / genetics
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / mortality
  • Piperazines / therapeutic use
  • Pyrimidines / therapeutic use*
  • Thiazoles / therapeutic use*
  • Time
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • Benzamides
  • Piperazines
  • Pyrimidines
  • Thiazoles
  • Imatinib Mesylate
  • Fusion Proteins, bcr-abl
  • Dasatinib

Associated data

  • ClinicalTrials.gov/NCT00123474