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

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
Externally publishedYes

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Leukemia, Myeloid, Chronic Phase
Cytogenetics
Imatinib Mesylate
Dasatinib
Disease-Free Survival
Survival Rate

Keywords

  • Chronic myeloid leukemia
  • Dasatinib
  • Drug resistance
  • Imatinib

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

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

In: Cancer, Vol. 115, No. 18, 15.09.2009, p. 4136-4147.

Research output: Contribution to journalArticle

Kantarjian, H, Pasquini, R, Lévy, V, Jootar, S, Holowiecki, J, Hamerschlak, N, Hughes, T, Bleickardt, E, Dejardin, D, Cortes, J & Shah, NP 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, vol. 115, no. 18, pp. 4136-4147. https://doi.org/10.1002/cncr.24504
Kantarjian, Hagop ; Pasquini, Ricardo ; Lévy, Vincent ; Jootar, Saengsuree ; Holowiecki, Jerzy ; Hamerschlak, Nelson ; Hughes, Timothy ; Bleickardt, Eric ; Dejardin, David ; Cortes, Jorge ; Shah, Neil P. / 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). In: Cancer. 2009 ; Vol. 115, No. 18. pp. 4136-4147.
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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.",
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T1 - Dasatinib or high-dose imatinib for chronic-phase chronic myeloid leukemia resistant to imatinib at a dose of 400 to 600 milligrams daily

T2 - Two-year follow-up of a randomized phase 2 study (START-R)

AU - Kantarjian, Hagop

AU - Pasquini, Ricardo

AU - Lévy, Vincent

AU - Jootar, Saengsuree

AU - Holowiecki, Jerzy

AU - Hamerschlak, Nelson

AU - Hughes, Timothy

AU - Bleickardt, Eric

AU - Dejardin, David

AU - Cortes, Jorge

AU - Shah, Neil P.

PY - 2009/9/15

Y1 - 2009/9/15

N2 - 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.

AB - 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.

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KW - Drug resistance

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