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- Title
Design and rationale for the life after stopping tyrosine kinase inhibitors (LAST) study, a prospective, single-group longitudinal study in patients with chronic myeloid leukemia.
- Authors
Atallah, Ehab; Schiffer, Charles A.; Weinfurt, Kevin P.; Zhang, Mei-Jie; Radich, Jerald P.; Oehler, Vivian G.; Pinilla-Ibarz, Javier; Deininger, Michael W. N.; Li Lin; Larson, Richard A.; Mauro, Michael J.; Moore, Joseph O.; Ritchie, Ellen K.; Shah, Neil P.; Silver, Richard T.; Wadleigh, Martha; Cortes, Jorge; Thompson, James; Guhl, Jessica; Horowitz, Mary M.
- Abstract
<bold>Background: </bold>Treatment of chronic myeloid leukemia with a tyrosine kinase inhibitor (TKI) offers significant improvements over previous treatments in terms of survival and toxicity yet nevertheless is associated with reduced health-related quality of life and very high cost. Several small studies from Europe and Australia suggested that discontinuing TKIs with regular monitoring was safe.<bold>Methods: </bold>The Life After Stopping TKIs (LAST) study is a large, U.S.-based study that aims to improve the evidence for clinical decision making regarding TKI discontinuation with monitoring in patients with chronic myeloid leukemia who have a deep molecular response to TKI therapy. The LAST study is a non-randomized, prospective, single-group longitudinal study of 173 patients. The co-primary objectives are to determine the proportion of patients who develop molecular recurrence (> 0.1% BCR-ABLIS) after discontinuing one of four TKIs (imatinib, dasatinib, nilotinib, or bosutinib) and to compare the patient-reported health status of patients before and after stopping TKIs. Outcomes are assessed at baseline and throughout the 36-month study follow-up period with a central laboratory used for blood samples. All samples with undetectable BCR-ABL are also examined using digital polymerase chain reaction, which is a more sensitive nanofluidic polymerase chain reaction system.<bold>Discussion: </bold>Because of their high cost and side effects, discontinuation of TKIs for patients with chronic myeloid leukemia who have a deep molecular response to TKI therapy is a promising approach to treatment. The LAST study is the largest U.S.-based TKI discontinuation study. It is the first to allow participation from patients on any of 4 first- and second-generation TKIs, includes a robust approach to measurement of clinical and patient-reported outcomes, and is using digital polymerase chain reaction to explore better prediction of safe discontinuation.<bold>Trial Registration: </bold>This study was registered prospectively on October 21, 2014 and assigned trial number NCT02269267 .
- Subjects
ANTINEOPLASTIC agents; PROTEIN kinase inhibitors; DRUG therapy; EXPERIMENTAL design; LONGITUDINAL method; EVALUATION of medical care; MEDICAL protocols; PROTEINS; QUALITY of life; RESEARCH funding; DISEASE relapse; PSYCHOLOGY; CHRONIC myeloid leukemia; DIAGNOSIS; THERAPEUTICS
- Publication
BMC Cancer, 2018, Vol 18, Issue 1, p1
- ISSN
1471-2407
- Publication type
journal article
- DOI
10.1186/s12885-018-4273-1