SUMMARY: This multicenter international phase III study evaluated the efficacy of Dasatinib (SPRYCEL®) versus Imatinib (GLEEVEC®) in newly diagnosed chronic phase Chronic Myeloid Leukemia patients. Of the 519 patients enrolled, 259 patients received SPRYCEL® at 100 mg daily whereas 260 patients received GLEEVEC® 400 mg daily. The complete cytogenetic response rate after one year for SPRYCEL® and GLEEVEC® was 77% versus 66% respectively and the major molecular response rate at 12 months was 46% vs 28% for the SPRYCEL® group and GLEEVEC® group respectively. Thrombocytopenia and pleural effusions were more often seen in the SPRYCEL® group. It was concluded that SPRYCEL® resulted in a significantly shorter time to achieve complete cytogenetic and major molecular responses. N Engl J Med 2010; 362:2260-2270.
Tag: Chronic Myeloid Leukemia
Nilotinib versus Imatinib for Newly Diagnosed Chronic Myeloid Leukemia
SUMMARY: ENESTnd (Evaluating Nilotinib Efficacy and Safety in Clinical Trials-Newly Diagnosed Patients) is a phase III, randomized, open-label, multicenter study comparing the efficacy and safety of Nilotinib (TASIGNA®), either 300 mg or 400 mg bid with GLEEVEC® (Imatinib) 400mg qd, in patients with newly diagnosed Ph+ CML in chronic phase. Of the 846 patients enrolled, 282 patients received TASIGNA® 300 mg bid, 281 patients received TASIGNA® 400 mg bid and 283 patients received GLEEVEC® 400 mg qd. With a median follow up of 18 months, the MMR (Major Molecular Response) was 66% for the TASIGNA® 300 mg bid group and 62% for the TASIGNA® 400 mg bid group compared with 40% for the GLEEVEC® 400 mg qd group. The median time to MMR amongst the patients who achieved MMR was faster for TASIGNA® 300 mg bid (5.7 months) and TASIGNA® 400 mg bid (5.8 months) groups of patients compared with GLEEVEC® 400 mg qd (8.3 months). The rates of complete cytogenetic response at 18 months were also significantly higher for both TASIGNA® groups – 85% in the TASIGNA® 300 mg bid group, 82% in the TASIGNA® 400 mg bid group and 74% in the GLEEVEC® 400 mg qd group. Fewer patients in the TASIGNA® groups progressed to accelerated phase or blast crises compared with GLEEVEC® group. Adverse effects more often seen with TASIGNA® included skin rash, headache, liver function abnormalities, high cholesterol, hyperglycemia, increased serum lipase, abnormal electrolyte levels and prolongation of the QT interval. The authors concluded that TASIGNA® at both 300 mg bid and 400 mg bid induced significantly higher and faster rates of MMR and complete cytogenetic remission compared with GLEEVEC® 400 mg qd. J Clin Oncol 28:15s, 2010 (suppl; abstr 6501)
Oncoprescribe Blog Remember Homoharringtonine? It may soon be in the limelight
This plant alkaloid originally isolated from the evergreen tree Cephalotaxus and in use for acute and chronic leukemias for over 25 years in China, will soon become available in a semisynthetic formulation (omacetaxine). This agent has now been proven to be safe and effective in patients with Chronic Myeloid Leukemia (CML) with T315I mutation. It should be noted that approximately 15% of the patients resistant to imatinib and 30% resistant to dasatinib and nilotinib harbor T315I mutation. The mechanism of action of this compound is independent of tyrosine kinase inhibiton. This drug is administered as a subcutaneous injection and is a giant leap in overcoming resistance to Tyrosine Kinase Inhibitors (TKI) in CML patients.
Oncoprescribe Blog More progress in Chronic Myeloid Leukemia
Imatinib, a breakthru development in the treatment of CML has been the standard first line treatment for the past several years. This is about to change following presentations at the ASH 2009 and ASCO 2010 meetings.
In the first study Dasatinib was compared head to head with Imatinib in newly diagnosed patients with CML. The complete cytogenetic responses and major molecular responses were higher in the Dasatinib group and these responses were acheived sooner than in the Imatinib group.
In the second study Nilotinib compared to Imatinib in newly diagnosed CML patients resulted in superior complete cytogenetic and major molecular responses.
These second generation BCR-ABL tyrosine kinase inhibitors may take over as first line treatment of CML although economics could play a major role.