Phase 3 study of dasatinib 140 mg once daily versus 70 mg twice daily in patients with chronic myeloid leukemia in accelerated phase resistant or intolerant to imatinib: 15-Month median follow-up

Hagop Kantarjian, Jorge Cortes, Dong Wook Kim, Pedro Dorlhiac-Llacer, Ricardo Pasquini, John DiPersio, Martin C. Müller, Jerald P. Radich, H. Jean Khoury, Nina Khoroshko, M. Brigid Bradley-Garelik, Chao Zhu, Martin S. Tallman

Research output: Contribution to journalArticle

Abstract

Dasatinib is the most potent BCR-ABL inhibitor, with 325-fold higher potency than imatinib against unmutated BCR-ABL in vitro. Studies have demonstrated the benefits of dasatinib 70 mg twice daily in patients with accelerated-phase chronic myeloid leukemia intolerant or resistant to imatinib. A phase 3 study compared the efficacy and safety of dasatinib 140 mg once daily with the current twice-daily regimen. Here, results from the subgroup with accelerated-phase chronic myeloid leukemia (n = 317) with a median follow-up of 15 months (treatment duration, 0.03-31.15 months) are reported. Among patients randomized to once-daily (n = 158) or twice-daily (n = 159) treatment, rates of major hematologic and cytogenetic responses were comparable (major hematologic response, 66% vs 68%; major cytogenetic response, 39% vs 43%, respectively). Estimated progression-free survival rates at 24 months were 51% and 55%, whereas overall survival rates were 63% versus 72%. Once-daily treatment was associated with an improved safety profile. In particular, significantly fewer patients in the once-daily group experienced a pleural effusion (all grades, 20% vs 39% P < .001). These results demonstrate that dasatinib 140 mg once daily has similar efficacy to dasatinib 70 mg twice daily but with an improved safety profile. This trial is registered at www.clinicaltrials.gov as #CA180-035.

Original languageEnglish (US)
Pages (from-to)6322-6329
Number of pages8
JournalBlood
Volume113
Issue number25
DOIs
StatePublished - Nov 19 2009
Externally publishedYes

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Leukemia, Myeloid, Accelerated Phase
Safety
Cytogenetics
Survival Rate
Pleural Effusion
Disease-Free Survival
Therapeutics
Imatinib Mesylate
Dasatinib

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Phase 3 study of dasatinib 140 mg once daily versus 70 mg twice daily in patients with chronic myeloid leukemia in accelerated phase resistant or intolerant to imatinib : 15-Month median follow-up. / Kantarjian, Hagop; Cortes, Jorge; Kim, Dong Wook; Dorlhiac-Llacer, Pedro; Pasquini, Ricardo; DiPersio, John; Müller, Martin C.; Radich, Jerald P.; Khoury, H. Jean; Khoroshko, Nina; Bradley-Garelik, M. Brigid; Zhu, Chao; Tallman, Martin S.

In: Blood, Vol. 113, No. 25, 19.11.2009, p. 6322-6329.

Research output: Contribution to journalArticle

Kantarjian, H, Cortes, J, Kim, DW, Dorlhiac-Llacer, P, Pasquini, R, DiPersio, J, Müller, MC, Radich, JP, Khoury, HJ, Khoroshko, N, Bradley-Garelik, MB, Zhu, C & Tallman, MS 2009, 'Phase 3 study of dasatinib 140 mg once daily versus 70 mg twice daily in patients with chronic myeloid leukemia in accelerated phase resistant or intolerant to imatinib: 15-Month median follow-up', Blood, vol. 113, no. 25, pp. 6322-6329. https://doi.org/10.1182/blood-2008-11-186817
Kantarjian, Hagop ; Cortes, Jorge ; Kim, Dong Wook ; Dorlhiac-Llacer, Pedro ; Pasquini, Ricardo ; DiPersio, John ; Müller, Martin C. ; Radich, Jerald P. ; Khoury, H. Jean ; Khoroshko, Nina ; Bradley-Garelik, M. Brigid ; Zhu, Chao ; Tallman, Martin S. / Phase 3 study of dasatinib 140 mg once daily versus 70 mg twice daily in patients with chronic myeloid leukemia in accelerated phase resistant or intolerant to imatinib : 15-Month median follow-up. In: Blood. 2009 ; Vol. 113, No. 25. pp. 6322-6329.
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abstract = "Dasatinib is the most potent BCR-ABL inhibitor, with 325-fold higher potency than imatinib against unmutated BCR-ABL in vitro. Studies have demonstrated the benefits of dasatinib 70 mg twice daily in patients with accelerated-phase chronic myeloid leukemia intolerant or resistant to imatinib. A phase 3 study compared the efficacy and safety of dasatinib 140 mg once daily with the current twice-daily regimen. Here, results from the subgroup with accelerated-phase chronic myeloid leukemia (n = 317) with a median follow-up of 15 months (treatment duration, 0.03-31.15 months) are reported. Among patients randomized to once-daily (n = 158) or twice-daily (n = 159) treatment, rates of major hematologic and cytogenetic responses were comparable (major hematologic response, 66{\%} vs 68{\%}; major cytogenetic response, 39{\%} vs 43{\%}, respectively). Estimated progression-free survival rates at 24 months were 51{\%} and 55{\%}, whereas overall survival rates were 63{\%} versus 72{\%}. Once-daily treatment was associated with an improved safety profile. In particular, significantly fewer patients in the once-daily group experienced a pleural effusion (all grades, 20{\%} vs 39{\%} P < .001). These results demonstrate that dasatinib 140 mg once daily has similar efficacy to dasatinib 70 mg twice daily but with an improved safety profile. This trial is registered at www.clinicaltrials.gov as #CA180-035.",
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AU - Cortes, Jorge

AU - Kim, Dong Wook

AU - Dorlhiac-Llacer, Pedro

AU - Pasquini, Ricardo

AU - DiPersio, John

AU - Müller, Martin C.

AU - Radich, Jerald P.

AU - Khoury, H. Jean

AU - Khoroshko, Nina

AU - Bradley-Garelik, M. Brigid

AU - Zhu, Chao

AU - Tallman, Martin S.

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