Dasatinib or high-dose imatinib for chronic-phase chronic myeloid leukemia resistant to imatinib at a dose of 400 to 600 milligrams daily: two-year follow-up of a randomized phase 2 study (START-R).
BACKGROUND
In patients with chronic-phase chronic myeloid leukemia (CP-CML), imatinib resistance is of increasing importance. Imatinib dose escalation was the main treatment option before dasatinib, which has 325-fold more potent inhibition than imatinib against unmutated Bcr-Abl in vitro. Data with a minimum of 2 years of follow-up were available for the current study of dasatinib and high-dose imatinib in CP-CML resistant to imatinib at daily doses from 400 mg to 600 mg.


METHODS
A phase 2, open-label study was initiated of 150 patients with imatinib-resistant CP-CML who were randomized (2:1) to receive either dasatinib 70 mg twice daily (n=101) or high-dose imatinib 800 mg (400 mg twice daily; n=49).


RESULTS
At a minimum follow-up of 2 years, dasatinib demonstrated higher rates of complete hematologic response (93% vs 82%; P=.034), major cytogenetic response (MCyR) (53% vs 33%; P=.017), and complete cytogenetic response (44% vs 18%; P=.0025). At 18 months, the MCyR was maintained in 90% of patients on the dasatinib arm and in 74% of patients on the high-dose imatinib arm. Major molecular response rates also were more frequent with dasatinib than with high-dose imatinib (29% vs 12%; P=.028). The estimated progression-free survival also favored dasatinib (unstratified log-rank test; P=.0012).


CONCLUSIONS
After 2 years of follow-up, dasatinib demonstrated durable responses and improved response and progression-free survival rates relative to high-dose imatinib.
Kantarjian
Hagop
H
Department of Leukemia, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77230-1402, USA. hkantarj@mdanderson.org
Pasquini
Ricardo
R
Lévy
Vincent
V
Jootar
Saengsuree
S
Holowiecki
Jerzy
J
Hamerschlak
Nelson
N
Hughes
Timothy
T
Bleickardt
Eric
E
Dejardin
David
D
Cortes
Jorge
J
Shah
Neil P
NP
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001549:Benzamides; D018592:Cross-Over Studies; D000069439:Dasatinib; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D019008:Drug Resistance, Neoplasm; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D000068877:Imatinib Mesylate; D015466:Leukemia, Myeloid, Chronic-Phase / Q000188:drug therapy*; D008875:Middle Aged; D010879:Piperazines / Q000008:administration & dosage* / Q000009:adverse effects; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011743:Pyrimidines / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use*; D013844:Thiazoles / Q000009:adverse effects / Q000627:therapeutic use*; D028761:Withholding Treatment
D001549:Benzamides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D013844:Thiazoles; D000068877:Imatinib Mesylate; D000069439:Dasatinib