Long-term outcome with dasatinib after imatinib failure in chronic-phase chronic myeloid leukemia: follow-up of a phase 3 study

TY - JOUR

T1 - Long-term outcome with dasatinib after imatinib failure in chronic-phase chronic myeloid leukemia: follow-up of a phase 3 study

AU - Shah, Neil P

AU - Guilhot, François

AU - Cortes, Jorge E

AU - Schiffer, Charles A

AU - le Coutre, Philipp

AU - Brümmendorf, Tim H

AU - Kantarjian, Hagop M

AU - Hochhaus, Andreas

AU - Rousselot, Philippe

AU - Mohamed, Hesham

AU - Healey, Diane

AU - Cunningham, Michael

AU - Saglio, Giuseppe

PY - 2014

Y1 - 2014

N2 - 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.

AB - 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.

KW - Antineoplastic Agents

KW - Benzamides

KW - Disease-Free Survival

KW - Drug Resistance, Neoplasm

KW - Follow-Up Studies

KW - Fusion Proteins, bcr-abl

KW - Humans

KW - Kaplan-Meier Estimate

KW - Leukemia, Myelogenous, Chronic, BCR-ABL Positive

KW - Piperazines

KW - Pyrimidines

KW - Thiazoles

KW - Time

KW - Treatment Outcome

U2 - 10.1182/blood-2013-10-532341

DO - 10.1182/blood-2013-10-532341

M3 - SCORING: Journal article

C2 - 24569263

VL - 123

SP - 2317

EP - 2324

JO - BLOOD

JF - BLOOD

SN - 0006-4971

IS - 15

ER -