TY - JOUR
T1 - Long-term response to imatinib is not affected by the initial dose in patients with Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase
T2 - Final update from the Tyrosine Kinase Inhibitor Optimization and Selectivity (TOPS) study
AU - Baccarani, Michele
AU - Druker, Brian J.
AU - Branford, Susan
AU - Kim, Dong Wook
AU - Pane, Fabrizio
AU - Mongay, Lidia
AU - Mone, Manisha
AU - Ortmann, Christine Elke
AU - Kantarjian, Hagop M.
AU - Radich, Jerald P.
AU - Hughes, Timothy P.
AU - Cortes, Jorge E.
AU - Guilhot, François
N1 - Funding Information:
Acknowledgments This work was supported by research funding from Novartis Pharmaceuticals Corporation. We thank Erinn Goldman, Ph.D. (ArticulateScience, LLC), for medical editorial assistance with this manuscript. We would also like to thank all investigators and patients who participated in the TOPS trial.
PY - 2014/5
Y1 - 2014/5
N2 - The TOPS trial evaluated high- (800 mg/day; n = 319) versus standard-dose (400 mg/day; n = 157) imatinib in patients newly diagnosed with Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase. Patients had a minimum follow-up of 42 months or discontinued early. Major molecular response (MMR) rates were similar between arms at (51.6 vs 50.2 % for 400 and 800 mg/day, respectively; P = 0.77) and by (75.8 vs 79.0 %; P = 0.4807) 42 months. There were no differences in event-free survival (EFS), progression-free survival (PFS), or overall survival (OS) between arms. The estimated rates of PFS on treatment and OS at 42 months were significantly higher in patients with MMR at 6, 12, and 18 months compared with those without MMR. Adverse events were more frequent with high-dose imatinib. Patients with ≤1 treatment interruption (vs >1) and those able to maintain imatinib ≥600 mg/day (vs <600 mg/day) in the first year of treatment had faster and higher response rates, but no improvement in EFS or PFS. Adherence to prescribed dose without interruption may be more important than initiation of therapy with higher doses of imatinib. Achievement of MMR correlated with long-term clinical outcomes.
AB - The TOPS trial evaluated high- (800 mg/day; n = 319) versus standard-dose (400 mg/day; n = 157) imatinib in patients newly diagnosed with Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase. Patients had a minimum follow-up of 42 months or discontinued early. Major molecular response (MMR) rates were similar between arms at (51.6 vs 50.2 % for 400 and 800 mg/day, respectively; P = 0.77) and by (75.8 vs 79.0 %; P = 0.4807) 42 months. There were no differences in event-free survival (EFS), progression-free survival (PFS), or overall survival (OS) between arms. The estimated rates of PFS on treatment and OS at 42 months were significantly higher in patients with MMR at 6, 12, and 18 months compared with those without MMR. Adverse events were more frequent with high-dose imatinib. Patients with ≤1 treatment interruption (vs >1) and those able to maintain imatinib ≥600 mg/day (vs <600 mg/day) in the first year of treatment had faster and higher response rates, but no improvement in EFS or PFS. Adherence to prescribed dose without interruption may be more important than initiation of therapy with higher doses of imatinib. Achievement of MMR correlated with long-term clinical outcomes.
KW - BCR-ABL
KW - Chronic myeloid leukemia
KW - Imatinib
KW - Phase 3 clinical trial
KW - Tyrosine kinase inhibitor
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U2 - 10.1007/s12185-014-1566-2
DO - 10.1007/s12185-014-1566-2
M3 - Article
C2 - 24658916
AN - SCOPUS:84901601715
SN - 0925-5710
VL - 99
SP - 616
EP - 624
JO - International Journal of Hematology
JF - International Journal of Hematology
IS - 5
ER -