title: Dasatinib in imatinib-resistant or -intolerant chronic-phase, chronic myeloid leukemia patients: 7-year follow-up of study CA180-034.
abstract: Dasatinib was approved at 100 mg once daily for imatinib-resistant or -intolerant patients with chronic myeloid leukemia (CML) in chronic phase, based on results of the phase 3 CA180-034 (NCT00123474) study. Here we present the final 7-year analysis of this pivotal study, the longest follow-up to date of any second-generation BCR-ABL1 tyrosine kinase inhibitor (TKI). Patients (n = 670) with imatinib-resistant or -intolerant CML in chronic phase received dasatinib. Nineteen percent of patients continued on study treatment, with a greater proportion in the 100 mg once daily arm remaining on therapy. Seven-year rates for major molecular response (MMR), progression-free survival (PFS), and overall survival (OS) were similar across doses; MMR, PFS, and OS results were 46, 42, and 65% at 100 mg once daily, respectively. Improved PFS and OS rates were reported in patients who achieved BCR-ABL1 ≤10% at 3 and 6 months. No new safety signals were identified. The incidence of drug-related pleural effusion was 28% at 100 mg once daily and 35% at the other three dose groups. Incidence of drug-related pulmonary hypertension and pulmonary arterial hypertension remained low (≤3% across all doses). Arterial ischemic events occurred in ≤4% of patients across all doses. These data support the long-term efficacy and well-established safety profile of dasatinib for patients with imatinib-resistant or -intolerant CML in chronic phase. Am. J. Hematol. 91:869-874, 2016. © 2016 Wiley Periodicals, Inc.
authors.affiliation: UCSF School of Medicine, San Francisco, California.
authors.forename: Neil P
authors.initials: NP
authors.lastname: Shah
authors.affiliation: Hôpital André Mignot and Université Versailles Saint-Quentin-en-Yvelines, Versailles, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Rousselot
authors.affiliation: Wayne State University School of Medicine, Detroit, Michigan.
authors.forename: Charles
authors.initials: C
authors.lastname: Schiffer
authors.affiliation: Saint Louis Hospital, Paris, France.
authors.forename: Delphine
authors.initials: D
authors.lastname: Rea
authors.affiliation: University of Texas M.D. Anderson Cancer Center, Houston, Texas.
authors.forename: Jorge E
authors.initials: JE
authors.lastname: Cortes
authors.affiliation: Hospital Italiano De La Plata, La Plata, Argentina.
authors.forename: Jorge
authors.initials: J
authors.lastname: Milone
authors.affiliation: Bristol-Myers Squibb, Princeton, New Jersey.
authors.forename: Hesham
authors.initials: H
authors.lastname: Mohamed
authors.affiliation: Bristol-Myers Squibb, Princeton, New Jersey.
authors.forename: Diane
authors.initials: D
authors.lastname: Healey
authors.affiliation: University of Texas M.D. Anderson Cancer Center, Houston, Texas.
authors.forename: Hagop
authors.initials: H
authors.lastname: Kantarjian
authors.affiliation: Universitätsklinikum Jena, Jena, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Hochhaus
authors.affiliation: University of Turin, Turin, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Saglio
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use; D000069439:Dasatinib / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm; D005500:Follow-Up Studies; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000150:complications / Q000188:drug therapy*; D015466:Leukemia, Myeloid, Chronic-Phase / Q000150:complications / Q000188:drug therapy*; D010198:Pancytopenia / Q000139:chemically induced; D061214:Patient Safety; D010996:Pleural Effusion / Q000139:chemically induced; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D000068877:Imatinib Mesylate; D000069439:Dasatinib