Relative survival in patients with chronic-phase chronic myeloid leukaemia in the tyrosine-kinase inhibitor era: analysis of patient data from six prospective clinical trials

Sasaki, Koji; Strom, Sara S.; O’Brien, Susan; Jabbour, Elias; Ravandi, Farhad; Konopleva, Marina; Borthakur, Gautam; Pemmaraju, Naveen; Jain, Preetesh; Pierce, Sherry; Kantarjian, Hagop M.; Cortes, Jorge

doi:10.1016/s2352-3026(15)00048-4

Cited by 231 publications

(157 citation statements)

References 29 publications

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“…Patients with CML are now living almost as long as the general population. 29 Therefore, given high OS rates (approximately 90% at 5 years) and a majority of patients achieving CCyR, a larger population over a longer period of time may demonstrate a statistically significant survival difference. Another possible explanation for indistinguishable survival benefit is that 26% of patients were treated with the second-generation TKIs dasatinib (16%) or nilotinib (9%) after discontinuation of imatinib, which can rescue patients with imatinib failure.…”

Section: Discussionmentioning

confidence: 99%

Final 5-Year Study Results of DASISION: The Dasatinib Versus Imatinib Study in Treatment-Naïve Chronic Myeloid Leukemia Patients Trial

Cortes

Saglio

Kantarjian

et al. 2016

JCO

723

771

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Purpose We report the 5-year analysis from the phase III Dasatinib Versus Imatinib Study in Treatment-Naïve Chronic Myeloid Leukemia Patients (DASISION) trial, evaluating long-term efficacy and safety outcomes of patients with chronic myeloid leukemia (CML) in chronic phase (CP) treated with dasatinib or imatinib. Patients and Methods Patients with newly diagnosed CML-CP were randomly assigned to receive dasatinib 100 mg once daily (n = 259) or imatinib 400 mg once daily (n = 260). Results At the time of study closure, 61% and 63% of dasatinib- and imatinib-treated patients remained on initial therapy, respectively. Cumulative rates of major molecular response and molecular responses with a 4.0- or 4.5-log reduction in BCR-ABL1 transcripts from baseline by 5 years remained statistically significantly higher for dasatinib compared with imatinib. Rates for progression-free and overall survival at 5 years remained high and similar across treatment arms. In patients who achieved BCR-ABL1 ≤ 10% at 3 months (dasatinib, 84%; imatinib, 64%), improvements in progression-free and overall survival and lower rates of transformation to accelerated/blast phase were reported compared with patients with BCR-ABL1 greater than 10% at 3 months. Transformation to accelerated/blast phase occurred in 5%and 7%of patients in the dasatinib and imatinib arms, respectively. Fifteen dasatinib-treated and 19 imatinib-treated patients had BCR-ABL1 mutations identified at discontinuation. There were no new or unexpected adverse events identified in either treatment arm, and pleural effusion was the only drug-related, nonhematologic adverse event reported more frequently with dasatinib (28% v 0.8% with imatinib). First occurrences of pleural effusion were reported with dasatinib, with the highest incidence in year 1. Arterial ischemic events were uncommon in both treatment arms. Conclusion These final results from the DASISION trial continue to support dasatinib 100 mg once daily as a safe and effective first-line therapy for the long-term treatment of CML-CP.

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Section: Discussionmentioning

confidence: 99%

Final 5-Year Study Results of DASISION: The Dasatinib Versus Imatinib Study in Treatment-Naïve Chronic Myeloid Leukemia Patients Trial

Cortes

Saglio

Kantarjian

et al. 2016

JCO

723

771

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“…9 Most patients with chronic myeloid leukemia who are treated with tyrosine kinase inhibitors experience near normal life expectancy, particularly those diagnosed before age 65 years, based on a recent review of clinical trial data. 36 Although historical groupings of lymphoid malignancies are still used to track progress, they do not reflect the substantial biologic variation by subtype that is captured by the more contemporary World Health Organization classification system. 37 In contrast to the steady increase in survival for most cancers, advances have been slow for lung and pancreatic cancers, for which the 5-year relative survival is currently 18% and 8%, respectively (Fig.…”

Section: Trends In Cancer Survivalmentioning

confidence: 99%

Cancer statistics, 2017

Siegel

Miller

Jemal

2017

CA A Cancer J Clinicians

13,975

10,267

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, 1,688,780 new cancer cases and 600,920 cancer deaths are projected to occur in the United States. For all sites combined, the cancer incidence rate is 20% higher in men than in women, while the cancer death rate is 40% higher. However, sex disparities vary by cancer type. For example, thyroid cancer incidence rates are 3-fold higher in women than in men (21 vs 7 per 100,000 population), despite equivalent death rates (0.5 per 100,000 population), largely reflecting sex differences in the "epidemic of diagnosis." Over the past decade of available data, the overall cancer incidence rate (2004)(2005)(2006)(2007)(2008)(2009)(2010)(2011)(2012)(2013) was stable in women and declined by approximately 2% annually in men, while the cancer death rate (2005)(2006)(2007)(2008)(2009)(2010)(2011)(2012)(2013)(2014) declined by about 1.5% annually in both men and women. From 1991 to 2014, the overall cancer death rate dropped 25%, translating to approximately 2,143,200 fewer cancer deaths than would have been expected if death rates had remained at their peak. Although the cancer death rate was 15% higher in blacks than in whites in 2014, increasing access to care as a result of the Patient Protection and Affordable Care Act may expedite the narrowing racial gap; from 2010 to 2015, the proportion of blacks who were uninsured halved, from 21% to 11%, as it did for Hispanics (31% to 16%). Gains in coverage for traditionally underserved Americans will facilitate the broader application of existing cancer control knowledge across every segment of the population. CA Cancer J Clin 2017;67:7-30.

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“…Chronic phase CML patients treated with TKIs in clinical trials in the MD Anderson Cancer Center since 2000 had a 5-year overall survival estimated at 94.7% relative to the general population of the United States. 2 Results from clinical trials in centers of excellence are frequently better than "real world" results, but population-based registries also confirm the improvement in survival since the introduction of TKIs. Based on data primarily from the first half of the decade in which TKIs were introduced, the 5-year relative survival was ;70%, in comparison with relative survival as low as 10% to 20% a decade earlier when interferon (IFN)-a or allogeneic stem cell transplantation was the standard of care.…”

Section: Success Of Tki Therapymentioning

confidence: 99%

Moving treatment-free remission into mainstream clinical practice in CML

Hughes

Ross

2016

Blood

277

246

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The dramatic success of tyrosine kinase inhibitors (TKIs) has led to the widespread perception that chronic myeloid leukemia (CML) has become another chronic disease, where lifelong commitment to pharmacologic control is the paradigm. Recent trials demonstrate that some CML patients who have achieved stable deep molecular response can safely cease their therapy without relapsing (treatment free remission [TFR]). Furthermore, those who are unsuccessful in their cessation attempt can safely re-establish remission after restarting their TKI therapy. Based on the accumulated data on TFR, we propose that it is now time to change our approach for the many CML patients who have achieved a stable deep molecular response on long-term TKI therapy. Perhaps half of these patients could successfully achieve TFR if offered the opportunity. For many of these patients ongoing therapy is impairing quality of life and imposing a heavy financial burden while arguably achieving nothing. This recommendation is based on the evident safety of cessation attempts and TFR in the clinical trial setting. We acknowledge that there are potential risks associated with cessation attempts in wider clinical practice, but this should not deter us. Instead we need to establish criteria for safe and appropriate TKI cessation. Clinical trials will enable us to define the best strategies to achieve TFR, but clinicians need guidance today about how to approach this issue with their patients. We outline circumstances in which it would be in the patient's best interest to continue TKI, as well as criteria for a safe TFR attempt.

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Relative survival in patients with chronic-phase chronic myeloid leukaemia in the tyrosine-kinase inhibitor era: analysis of patient data from six prospective clinical trials

Cited by 231 publications

References 29 publications

Final 5-Year Study Results of DASISION: The Dasatinib Versus Imatinib Study in Treatment-Naïve Chronic Myeloid Leukemia Patients Trial

Final 5-Year Study Results of DASISION: The Dasatinib Versus Imatinib Study in Treatment-Naïve Chronic Myeloid Leukemia Patients Trial

Cancer statistics, 2017

Moving treatment-free remission into mainstream clinical practice in CML

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