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| |  Dasatinib Benefits Patients With Chronic-Phase CML Failing Imatinib: Presented at EHA By Emma Hitt, PhD COPENHAGEN, Denmark -- June 15, 2008 -- Dasatinib is superior to high-dose imatinib in patients with chronic-phase chronic myeloid leukaemia (CML) after failing standard-dose imatinib, according to data from the 24-month follow-up START-R study. Philippe Rousselot, MD, Service d'Hématologie et d'Oncologie, Hôpital Mignot, Versailles, France, and colleagues presented the findings here on June 13 at the 13th Congress of the European Hematology Association (EHA). According to the researchers, the second-generation tyrosine kinase inhibitor (TKI) dasatinib may override multiple mechanisms of imatinib resistance and, with the exception of T315I, is active against imatinib-resistant mutations. The phase 2 study included 150 patients with chronic-phase CML who failed standard-dose imatinib 400 to 600 mg QD and who had a minimum follow-up of 24 months. Patients received either dasatinib 70 mg BID (n = 101) or imatinib 800 mg QD (n = 49). The primary endpoint was major cytogenetic response (MCyR) rate at 12 weeks. Patients without MCyR at 12 weeks, those who experienced confirmed progression, or those with intolerance despite dose reduction were permitted to cross over to the other study therapy. In addition, patients in the dasatinib group with inadequate responses at 12 weeks or progression could be escalated to dasatinib 90 mg BID. The MCyR rate at 12 weeks was 36% for patients receiving dasatinib versus 29% receiving high-dose imatinib, which was not significantly different between arms. However, at last follow-up, 53% patients in the dasatinib arm and 33% in the high-dose imatinib arm had achieved MCyRs (P = .017), the difference thought to arise mainly from higher rates of complete cytogenetic response with dasatinib (44% vs 18%, P = .0025). MCyRs were also more durable in patients receiving dasatinib. After 18 months, 90% of dasatinib-treated patients maintained an MCyR, compared with 74% of imatinib-treated patients. At 24 months, dasatinib was associated with significantly higher major molecular response rates (29% vs 12%, P = .028). Of the patients receiving dasatinib, 59% were without failure at 24 months (P < .0001) versus 18% of those receiving imatinib. In addition, progression-free survival (PFS) rates at 24 months were higher with dasatinib: 86% versus 65% (P = .0012). The PFS for dasatinib was superior to that of high-dose imatinib regardless of whether patients had received imatinib 400 mg QD (P = .0562) or 600 mg QD (P = .0033) before entering the study. Approximately 20% of patients in both arms discontinued treatment due to treatment-related toxicities. Grade 3/4 cytopenias were more common in the dasatinib arm, while grade 3/4 nonhaematologic toxicities were comparable. "There seems to be an advantage for switching patients to dasatinib after they have failed imatinib standard dose," Dr. Rousselot said in an interview. "Not only are responses more common, but they are also more durable, so the sooner a patient failing imatinib is switched to dasatinib, the better," he said. [Presentation title: Dasatinib Compared With High-Dose Imatinib in Patients With Chronic Myelogenous Leukemia in Chronic Phase (CML-CP) After Failure of Standard-Dose Imatinib -- A Two-Year Update of the Start-R Study. Abstract 122.]
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