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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)

  1. Hagop Kantarjian MD1,§,*,
  2. Ricardo Pasquini MD2,
  3. Vincent Lévy MD, PhD3,
  4. Saengsuree Jootar MD4,
  5. Jerzy Holowiecki MD, PhD5,
  6. Nelson Hamerschlak MD, PhD6,
  7. Timothy Hughes MD7,
  8. Eric Bleickardt MD8,
  9. David Dejardin MSc8,
  10. Jorge Cortes MD1,
  11. Neil P. Shah MD, PhD9

Article first published online: 17 JUN 2009

DOI: 10.1002/cncr.24504

Issue

Cancer

Cancer

Volume 115, Issue 18, pages 4136–4147, 15 September 2009

Additional Information

How to Cite

Kantarjian, H., Pasquini, R., Lévy, V., Jootar, S., Holowiecki, J., Hamerschlak, N., Hughes, T., Bleickardt, E., Dejardin, D., Cortes, J. and 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. Cancer, 115: 4136–4147. doi: 10.1002/cncr.24504

Author Information

  1. 1

    Department of Leukemia, The University of Texas M. D. Anderson Cancer Center, Houston, Texas

  2. 2

    Hospital De Clinicas De Curitiba, Parana, Brazil

  3. 3

    Clinical Investigation Center, AP-HP, INSERM U9504, Hôpital Saint-Louis, Paris, France

  4. 4

    Ramathibodi Hospital, Mahidol University, Bangkok, Thailand

  5. 5

    University Hospital-SPSKM, Katowice, Poland

  6. 6

    Hospital Israelita Albert Einstein, Sao Paulo, Brazil

  7. 7

    Division of Hematology, Institute of Medical and Veterinary Science, Adelaide, South Australia, Australia

  8. 8

    Bristol-Myers Squibb, Wallingford, Connecticut

  9. 9

    Division of Hematology and Oncology, University of California at San Francisco School of Medicine, San Francisco, California

  1. §

    Fax: (713) 794-4297

*Department of Leukemia, Unit 428, The University of Texas M. D. Anderson Cancer Center, PO Box 301402, Houston, TX 77230-1402

  1. †

    Presented previously in part as an oral presentation at the 49th Annual Meeting and Exposition of the American Society of Hematology, Atlanta, Georgia, December 8-11, 2007; and as a poster presentation at the 44th Annual Meeting of the American Society of Clinical Oncology, Chicago, Illinois, May 30 to June 3, 2008; and at the 13th Congress of the European Hematology Association, Copenhagen, Denmark, June 12-15, 2008.

  2. ‡

    The following principal investigators, in addition to the authors, also participated in the CA180-017 study: J. J. Garcia, I. Otero, and D. Riveros (Argentina); C. Arthur (Australia); A. Bosly and W. Schroyens (Belgium); P. E. Dorlhiac Llacer and A. Moellman Coelho (Brazil); S. Assouline, D. Forrest, C. Gambacorti-Passerini, P. Laneuville, and A. Turner (Canada); M. Varik (Estonia); K. Porkka (Finland); T. Facon, F. Guilhot, M. Michalet, J. Reiffers, and P. Rousselot (France); C. Bokemeyer, A. Hochhaus, and D. Niederwieser (Germany); T. Masszi (Hungary); A. Nagler (Israel); D. W. Kim (Korea); H. Hjorth-Hansen (Norway); L. Casanova and J. Navarro (Peru); P. Caguioa (Philippines); A. Dmoszynska, W. Jedrzejczak, A. Hellmann, T. Robak, and A. Skotnicki (Poland); F. Cabanillas (Puerto Rico); N. Khoroshko, A. Zaritsky, and A. Golenkov (Russia); J. Lombard, P. Ruff, and G. Cohen (South Africa); L. Stenke and H. Wadenvik (Sweden); L. Y. Shih (Taiwan); J. Apperley, T. Holyoake, and S. O'Brien (United Kingdom); and J. Dipersio, J. K. Giguere, R. Lloyd, J. McGuirk, M. S. Murali, R. M. Stone, and R. Paquette (United States). In addition, K. Gialelis served as protocol manager, and A. Zhao and E. Cormier served as protocol data managers.

Publication History

  1. Issue published online: 4 SEP 2009
  2. Article first published online: 17 JUN 2009
  3. Manuscript Accepted: 10 FEB 2009
  4. Manuscript Received: 17 DEC 2008

Funded by

  • Bristol-Myers Squibb
  • Novartis
  • Wyeth

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Keywords:

  • dasatinib;
  • drug resistance;
  • imatinib;
  • chronic myeloid leukemia

The current study was a follow-up of a phase 2, open-label study of 150 patients with chronic-phase chronic myeloid leukemia who were resistant to imatinib and were randomized (2:1) to receive either dasatinib at a dose of 70 mg twice daily (n = 101) or high-dose imatinib at a dose of 800 mg (400 mg twice daily; n = 49). After 2 years of follow-up, dasatinib demonstrated durable responses and improved response and progression-free survival rates relative to high-dose imatinib.

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 progression-free survival rates relative to high-dose imatinib. Cancer 2009. © 2009 American Cancer Society.

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