Impact of exclusion criteria for the DASISION and ENESTnd trials in the front‐line treatment of a ‘real‐life’ patient population with chronic myeloid leukaemia

Abstract

Both Dasision and ENESTnd trials had many exclusion criteria, with a possible selection bias compared with the real-life. To address the impact of this bias on the first-line treatment in the current clinical practice, we revised 207 unselected newly diagnosed chronic phase chronic myeloid leukaemia (CML) patients [M/F 108/99, median age 58.8 years, interquartile range 42.3-70.2] treated with front-line imatinib from June 2002 to June 2013 at our Institution, and evaluated how many of them would have been excluded from enrolment in the two trials. Twenty-eight patients (13.5%) should have been excluded by both trials because of polycomorbidities (12), severe cardiomyopathy (five), age > 80 with frailty (three), drug abuse (two) or other severe concomitant diseases (six). In addition, eight patients should have been excluded by Dasision due to isolated chronic obstructive broncopulmonar disease, and 19 patients should have been excluded by ENESTnd due to isolated diabetes (10), arrhythmia (four), acute myocardial infarction > 6 months before CML diagnosis (two), chronic pancreatic disease (two) and peripheral arterial obstructive disease (one). On the whole, 36 patients (17.4%) would have been excluded by Dasision trial and 47 (22.7%) by ENESTnd trial. The patients potentially not eligible for both trials were significantly older and with imatinib had a worse outcome compared with patients potentially eligible. Our data highlight that an automatic transposition of results available in clinical controlled trials into the frontline real-life management of CML patients should be regarded with caution. Copyright © 2015 John Wiley & Sons, Ltd.

Second‐ or third‐generation tyrosine kinase inhibitors in first‐line treatment of chronic myeloid leukemia in general population: Is there a real benefit?

“…As expected, divergences were found in the study population between the patients enrolled and not enrolled in clinical trials: enrolled patients represented 22% of the treated population, were younger, and had a better overall condition and less severe co‐morbidities than non‐enrolled patients. These differences were also found by Latagliata et al 24 among patients non eligible for both DASISION and ENESTnd clinical trials. This justifies the interest of exploring the difference in relative effect of the two generations of TKIs used in first‐line treatment in the general population.…”

ENESTnd Trial: A Phase III Study Comparing Nilotinib with Imatinib as Front-Line Therapy of Early Chronic-Phase Chronic Myeloid Leukemia

“…Economic issues have become more and more prominent with the next availability of IM in a generic form, and the cry of alarm of a group of experts on the price of innovative cancer drugs such as TKIs [28]. On a medical point of view, all recent international guidelines advocate the use of either IM, nilotinib or dasatinib as front-line therapy of CP-CML [29][30][31] than 20%, experiences a poorer outcome than the potentially eligible one [32]. Food restrictions and b.i.d.…”

Excellent outcomes of 2G-TKI therapy after imatinib failure in chronic phase CML patients

“…The most widely used tools are BCR-ABL1 mutational status and patient's comorbidities. At present, however, only a small and definitive number of mutations have been shown to confer insensitivity to DAS (V299L and F317L/V/I/C), NIL (Y253H, E255K/V, and F359I/V/C) or both (T351I)[ 23 ], while the percentage of patients for whom a specific concomitant disease may preclude the use of one of the two 2G-TKIs does not exceed 20% [ 24 ]. Our study indicates that, in a “real life” setting, both DAS and NIL are equally effective, with high rates of cytogenetic and molecular responses, good persistence on therapy with acceptable toxicity and a significant chance to achieve a stable DMR.…”