SUMMARY: BOSULIF® (Bosutinib), an Abl and Src kinase inhibitor was approved by the FDA for the treatment of adult patients with chronic, accelerated, or blast phase Philadelphia chromosome-positive (Ph+) chronic myelogenous leukemia (CML) with resistance, or intolerance to prior therapy. This trial included CML patients treated with imatinib followed by a second generation TKI. Five hundred and forty six (546) patients were enrolled in a single-arm, open-label, multi-center trial and these patients had either chronic phase (CP), accelerated phase (AP) or blast phase (BP) CML and were previously treated with at least one prior tyrosine kinase inhibitor (TKI). The primary endpoints for patients with CP CML were the rate of major cytogenetic response (MCyR) at week 24 and the duration of MCyR. The primary endpoints for patients with AP or BP CML were the rate of confirmed complete hematologic response (CHR) and overall hematologic response (OHR) by week 48. The MCyR at week 24 was 34% for those CP CML patients who received prior therapy with one TKI and 27% for those who received prior therapy with more than one TKI. The duration of MCyR among 53% of the patients who achieved MCyR at any time during the trial was 18 months, for patients with CP CML who had been treated with one prior TKI. For those CP CML patients treated with more than one TKI, the duration of MCyR among 51% of the patients who achieved MCyR at any time during the trial was 9 months. The CHR and OHR for AP CML who received at least one prior TKI were 30% and 55% respectively at week 48 whereas the BP CML group had a CHR and OHR of 15% and 28% respectively at week 48. BOSULIF® will be a welcome addition for those CML patients who had progressed on one or more tyrosine kinase inhibitors. Brummendorf TH, Cortes JE, Kantarjian H, et al. J Clin Oncol 29: 2011 (suppl; abstr 6535)
Tag: Chronic Myeloid Leukemia
Dasatinib versus Imatinib in Newly Diagnosed Chronic-Phase Chronic Myeloid Leukemia
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.
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.