title: Long-term outcome with dasatinib after imatinib failure in chronic-phase chronic myeloid leukemia: follow-up of a phase 3 study.
abstract: We present long-term follow-up of a dasatinib phase 3 study of patients with imatinib-resistant/-intolerant chronic myeloid leukemia (CML). In the CA180-034 study, 670 patients with imatinib-resistant/-intolerant CML in chronic phase (CML-CP) received dasatinib 100 mg once daily, 50 mg twice daily, 140 mg once daily, or 70 mg twice daily. At 6 years, 188 (28%) of 670 patients remained on study treatment. Estimated 6-year protocol-defined progression-free survival (PFS) rates were 49%, 51%, 40%, and 47%, respectively, and estimated 6-year overall survival (OS) rates were 71%, 74%, 77%, and 70%, respectively (intent-to-treat population, including protocol-defined progression or death after discontinuation). Estimated 6-year rates of survival without transformation on study treatment were 76%, 80%, 83%, and 74%, respectively. Major molecular response was achieved in 43% (100 mg once daily) and 40% (all other arms) of patients by 6 years. Molecular and cytogenetic responses at 3 and 6 months were highly predictive of PFS and OS. Notably, estimated 6-year PFS rates based on ≤1%, >1% to 10%, and >10% BCR-ABL transcripts at 3 months were 68%, 58%, and 26%, respectively. Most adverse events occurred by 2 years. Imatinib-resistant/-intolerant patients with CML-CP can experience long-term benefit with dasatinib therapy, particularly if achieving BCR-ABL ≤10% at 3 months. This study was registered at ClinicalTrials.gov: NCT00123474.
authors.affiliation: University of California at San Francisco School of Medicine, San Francisco, CA;
authors.forename: Neil P
authors.initials: NP
authors.lastname: Shah
authors.forename: François
authors.initials: F
authors.lastname: Guilhot
authors.forename: Jorge E
authors.initials: JE
authors.lastname: Cortes
authors.forename: Charles A
authors.initials: CA
authors.lastname: Schiffer
authors.forename: Philipp
authors.initials: P
authors.lastname: le Coutre
authors.forename: Tim H
authors.initials: TH
authors.lastname: Brümmendorf
authors.forename: Hagop M
authors.initials: HM
authors.lastname: Kantarjian
authors.forename: Andreas
authors.initials: A
authors.lastname: Hochhaus
authors.forename: Philippe
authors.initials: P
authors.lastname: Rousselot
authors.forename: Hesham
authors.initials: H
authors.lastname: Mohamed
authors.forename: Diane
authors.initials: D
authors.lastname: Healey
authors.forename: Michael
authors.initials: M
authors.lastname: Cunningham
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Saglio
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001549:Benzamides / Q000627:therapeutic use; D000069439:Dasatinib; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm; D005500:Follow-Up Studies; D016044:Fusion Proteins, bcr-abl / Q000097:blood; D006801:Humans; D000068877:Imatinib Mesylate; D053208:Kaplan-Meier Estimate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D010879:Piperazines / Q000627:therapeutic use; D011743:Pyrimidines / Q000627:therapeutic use*; D013844:Thiazoles / Q000627:therapeutic use*; D013995:Time; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D013844:Thiazoles; D000068877:Imatinib Mesylate; D016044:Fusion Proteins, bcr-abl; D000069439:Dasatinib