Final 5-Year Study Results of DASISION: The Dasatinib Versus Imatinib Study in Treatment-Naïve Chronic Myeloid Leukemia Patients Trial

Abstract

Purpose: We report the 5-year analysis from the phase III Dasatinib Versus Imatinib Study in Treatment-Naïve Chronic Myeloid Leukemia Patients (DASISION) trial, evaluating long-term efficacy and safety outcomes of patients with chronic myeloid leukemia (CML) in chronic phase (CP) treated with dasatinib or imatinib.

Patients and methods: Patients with newly diagnosed CML-CP were randomly assigned to receive dasatinib 100 mg once daily (n = 259) or imatinib 400 mg once daily (n = 260).

Results: At the time of study closure, 61% and 63% of dasatinib- and imatinib-treated patients remained on initial therapy, respectively. Cumulative rates of major molecular response and molecular responses with a 4.0- or 4.5-log reduction in BCR-ABL1 transcripts from baseline by 5 years remained statistically significantly higher for dasatinib compared with imatinib. Rates for progression-free and overall survival at 5 years remained high and similar across treatment arms. In patients who achieved BCR-ABL1 ≤ 10% at 3 months (dasatinib, 84%; imatinib, 64%), improvements in progression-free and overall survival and lower rates of transformation to accelerated/blast phase were reported compared with patients with BCR-ABL1 greater than 10% at 3 months. Transformation to accelerated/blast phase occurred in 5% and 7% of patients in the dasatinib and imatinib arms, respectively. Fifteen dasatinib-treated and 19 imatinib-treated patients had BCR-ABL1 mutations identified at discontinuation. There were no new or unexpected adverse events identified in either treatment arm, and pleural effusion was the only drug-related, nonhematologic adverse event reported more frequently with dasatinib (28% v 0.8% with imatinib). First occurrences of pleural effusion were reported with dasatinib, with the highest incidence in year 1. Arterial ischemic events were uncommon in both treatment arms.

Conclusion: These final results from the DASISION trial continue to support dasatinib 100 mg once daily as a safe and effective first-line therapy for the long-term treatment of CML-CP.

Conflict of interest statement

AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST Disclosures provided by the authors are available with this article at www.jco.org. AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO’s conflict of interest policy, please refer to www.asco.org/rwc or jco.ascopubs.org/site/ifc. Jorge E. Cortes Consulting or Advisory Role: ARIAD, Bristol-Myers Squibb, Novartis, Pfizer Research Funding: ARIAD (Inst), Bristol-Myers Squibb (Inst), Novartis (Inst), Pfizer (Inst), Teva (Inst) Giuseppe Saglio Consulting or Advisory Role: Bristol-Myers Squibb, Novartis, ARIAD, Pfizer Hagop M. Kantarjian Research Funding: Pfizer (Inst), ARIAD, Amgen (Inst), Bristol-Myers Squibb (Inst), Novartis (Inst) Michele Baccarani Honoraria: Bristol-Myers Squibb Consulting or Advisory Role: Bristol-Myers Squibb Speakers’ Bureau: Bristol-Myers Squibb Jiří Mayer Consulting or Advisory Role: Novartis, Bristol-Myers Squibb Research Funding: Novartis, Bristol-Myers Squibb Concepción Boqué Honoraria: Novartis, Bristol-Myers Squibb Consulting or Advisory Role: Novartis Travel, Accommodations, Expenses: Novartis, Bristol-Myers Squibb, Celgene Neil P. Shah Research Funding: Bristol-Myers Squibb, ARIAD, Pfizer, Daiichi Sankyo, Plexxikon Charles Chuah Honoraria: Bristol-Myers Squibb, Novartis Luis Casanova No relationship to disclose Brigid Bradley-Garelik Employment: Bristol-Myers Squibb Stock or Other Ownership: Bristol-Myers Squibb George Manos Employment: Bristol-Myers Squibb Stock or Other Ownership: Bristol-Myers Squibb Andreas Hochhaus Honoraria: Bristol-Myers Squibb, Novartis, Pfizer, ARIAD, Omniamed Consulting or Advisory Role: Novartis, Bristol-Myers Squibb, Pfizer, ARIAD Research Funding: Novartis (Inst), Bristol-Myers Squibb (Inst), Pfizer (Inst), ARIAD (Inst), MSD Travel, Accommodations, Expenses: Novartis, Bristol-Myers Squibb, Pfizer, ARIAD

© 2016 by American Society of Clinical Oncology.

Figures

Fig 1.

CONSORT diagram for the DASISION trial after a minimum follow-up of 5 years. CML-CP, chronic myeloid leukemia in chronic phase; Ph+, Philadelphia chromosome positive. (*) Reasons for discontinuation are listed in Table 1.

Fig 2.

Cumulative response rates over time. The percentages of patients with (A) major molecular response (MMR) and (B) molecular response with a 4.5-log reduction in BCR-ABL1 transcripts from baseline (MR4.5; BCR-ABL1 transcript level ≤ 0.0032% [International Scale]) by 1, 2, 3, 4, and 5 years are shown.

Fig 3.

Estimated 5-year (A, B) overall survival (OS) and (C, D) progression-free survival (PFS) by molecular response at 3 months for both treatment arms. OS and PFS were calculated using patients on study treatment and in follow-up after discontinuation of randomly assigned treatment.

Fig 4.

Drug-related, nonhematologic adverse events (AEs) reported in ≥ 10% of patients. Odds ratios (dasatinib v imatinib) with 95% CIs are shown for AEs that occurred in ≥ 10% of patients. Blue favors dasatinib, and gold favors imatinib.

Fig A1.

(A) Major molecular response (MMR) and (B) molecular response with a 4.5-log reduction in BCR-ABL1 transcripts from baseline (MR4.5; BCR-ABL1 transcript level ≤ 0.0032% [International Scale]) at any time by Euro (Hasford) risk score.

Fig A2.

Kaplan-Meier curves for (A) overall survival and (B) progression-free survival in both treatment arms. A sensitivity analysis of progression-free survival was performed to include patients who discontinued treatment and experienced progression or died on treatment or during follow-up.

Fig A3.

Expected survival by age at diagnosis for both treatment arms and a general population of patients without chronic myeloid leukemia. (*) Expected life span estimates were adapted from Ludwig et al.