Dasatinib versus Imatinib in Newly Diagnosed Chronic-Phase Chronic Myeloid Leukemia

Volume 362:2260-2270 June 17, 2010 Number 24

Dasatinib versus Imatinib in Newly Diagnosed Chronic-Phase Chronic Myeloid Leukemia

Hagop Kantarjian, M.D., Neil P. Shah, M.D., Ph.D., Andreas Hochhaus, M.D., Jorge Cortes, M.D., Sandip Shah, M.D., Manuel Ayala, M.D., Beatriz Moiraghi, M.D., Zhixiang Shen, M.D., Jiri Mayer, M.D., Ricardo Pasquini, M.D., Hirohisa Nakamae, M.D., Ph.D., Françoise Huguet, M.D., Concepción Boqué, M.D., Charles Chuah, M.R.C.P., M.D., Eric Bleickardt, M.D., M. Brigid Bradley-Garelik, M.D., Chao Zhu, Ph.D., Ted Szatrowski, M.D., David Shapiro, M.D., and Michele Baccarani, M.D.


ABSTRACT

Background Treatment with dasatinib, a highly potent BCR-ABL kinase inhibitor, has resulted in high rates of complete cytogenetic response and progression-free survival among patients with chronic myeloid leukemia (CML) in the chronic phase, after failure of imatinib treatment. We assessed the efficacy and safety of dasatinib, as compared with imatinib, for the first-line treatment of chronic-phase CML.

Methods In a multinational study, 519 patients with newly diagnosed chronic-phase CML were randomly assigned to receive dasatinib at a dose of 100 mg once daily (259 patients) or imatinib at a dose of 400 mg once daily (260 patients). The primary end point was complete cytogenetic response by 12 months, confirmed on two consecutive assessments at least 28 days apart. Secondary end points, including major molecular response, were tested at a significance level of 0.0001 to adjust for multiple comparisons.

Results After a minimum follow-up of 12 months, the rate of confirmed complete cytogenetic response was higher with dasatinib than with imatinib (77% vs. 66%, P=0.007), as was the rate of complete cytogenetic response observed on at least one assessment (83% vs. 72%, P=0.001). The rate of major molecular response was higher with dasatinib than with imatinib (46% vs. 28%, P<0.0001), and responses were achieved in a shorter time with dasatinib (P<0.0001). Progression to the accelerated or blastic phase of CML occurred in 5 patients who were receiving dasatinib (1.9%) and in 9 patients who were receiving imatinib (3.5%). The safety profiles of the two treatments were similar.

Conclusions Dasatinib, administered once daily, as compared with imatinib, administered once daily, induced significantly higher and faster rates of complete cytogenetic response and major molecular response. Since achieving complete cytogenetic response within 12 months has been associated with better long-term, progression-free survival, dasatinib may improve the long-term outcomes among patients with newly diagnosed chronic-phase CML. (ClinicalTrials.gov number, NCT00481247 [ClinicalTrials.gov] .)



Source Information

From the University of Texas M.D. Anderson Cancer Center, Houston (H.K., J.C.); University of California San Francisco School of Medicine, San Francisco (N.P.S.); the Department of Hematology and Oncology, Universitätsklinikum Jena, Jena, Germany (A.H.); Hemato-Oncology Clinic, Vedanta, Ahmedabad, India (S.S.); Hospital de Especialidades CMN "La Raza," Instituto Mexicano del Seguro Social, Mexico City (M.A.); Hospital General de Agudos J.M. Ramos Mejia, Buenos Aires (B.M.); Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai (Z.S.); Interni Hematoonkologicka Klinika, University Hospital Brno, Brno, Czech Republic (J.M.); Hospital de Clínicas de Curitiba, Parana, Brazil (R.P.); Graduate School of Medicine, Osaka City University, Osaka, Japan (H.N.); the Department of Hematology, Hôpital Purpan, Toulouse, France (F.H.); the Department of Clinical Hematology, Institut Català d'Oncologia, Hospitalet de Llobregat, Barcelona (C.B.); Singapore General Hospital, Duke-NUS Graduate Medical School, Singapore (C.C.); Bristol-Myers Squibb, Wallingford, CT (E.B., M.B.B.-G., C.Z., D.S.); Bristol-Myers Squibb, Princeton, NJ (T.S.); and the Department of Hematology–Oncology "L. and A. Seràgnoli," University of Bologna, Bologna, Italy (M.B.).

Drs. Kantarjian and Shah contributed equally to this article.

Investigators who participated in the Dasatinib versus Imatinib Study in Treatment-Naive CML Patients (DASISION) are listed in the Appendix.

This article (10.1056/NEJMoa1002315) was published on June 5, 2010, at NEJM.org.

Address reprint requests to Dr. Kantarjian at the Department of Leukemia, University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030, or at hkantarj@mdanderson.org.

open here to see the full-text:
http://content.nejm.org/cgi/content/short/362/24/2260