Dasatinib or high-dose imatinib for chronic-phase chronic myeloid leukemia resistant to imatinib at a dose of 400 to 600 milligrams daily: Two-year follow-up of a randomized phase 2 study (START-R)

Hagop Kantarjian, Ricardo Pasquini, Vincent Lévy, Saengsuree Jootar, Jerzy Holowiecki, Nelson Hamerschlak, Timothy Hughes, Eric Bleickardt, David Dejardin, Jorge Cortes, Neil P. Shah

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167 Citations (Scopus)


BACKGROUND: In patients with chronic-phase chronic myeloid leukemia (CP-CML), imatinib resistance is of increasing importance. Imatinib dose escalation was the main treatment option before dasatinib, which has 325-fold more potent inhibition than imatinib against unmutated Bcr-Abl in vitro. Data with a minimum of 2 years of follow-up were available for the current study of dasatinib and high-dose imatinib in CP-CML resistant to imatinib at daily doses from 400 mg to 600 mg. METHODS: A phase 2, open-label study was initiated of 150 patients with imatinib-resistant CP-CML who were randomized (2:1) to receive either dasatinib 70 mg twice daily (n = 101) or high-dose imatinib 800 mg (400 mg twice daily; n = 49). RESULTS: At a minimum follow-up of 2 years, dasatinib demonstrated higher rates of complete hematologic response (93% vs 82%; P = .034), major cytogenetic response (MCyR) (53% vs 33%; P = .017), and complete cytogenetic response (44% vs 18%; P = .0025). At 18 months, the MCyR was maintained in 90% of patients on the dasatinib arm and in 74% of patients on the high-dose imatinib arm. Major molecular response rates also were more frequent with dasatinib than with high-dose imatinib (29% vs 12%; P = .028). The estimated progression-free survival also favored dasatinib (unstratified log-rank test; P = .0012). CONCLUSIONS: After 2 years of follow-up, dasatinib demonstrated durable responses and improved response and progressionfree survival rates relative to high-dose imatinib.

Original languageEnglish
Pages (from-to)4136-4147
Number of pages12
Issue number18
Publication statusPublished - 15 Sep 2009


  • Chronic myeloid leukemia
  • Dasatinib
  • Drug resistance
  • Imatinib

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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