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

Research output: Contribution to journalArticle

165 Scopus citations

Abstract

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 (US)
Pages (from-to)4136-4147
Number of pages12
JournalCancer
Volume115
Issue number18
DOIs
StatePublished - Sep 15 2009

Keywords

  • Chronic myeloid leukemia
  • Dasatinib
  • Drug resistance
  • Imatinib

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of '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)'. Together they form a unique fingerprint.

  • Cite this

    Kantarjian, H., Pasquini, R., Lévy, V., Jootar, S., Holowiecki, J., Hamerschlak, N., Hughes, T., Bleickardt, E., Dejardin, D., Cortes, J., & Shah, N. P. (2009). 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). Cancer, 115(18), 4136-4147. https://doi.org/10.1002/cncr.24504