LITTLE FALLS, N.J., May 27 — Dasatinib (Sprycel) has received full FDA approval as second-line treatment for chronic myeloid leukemia (CML), Bristol-Myers Squibb, the drug’s maker, announced.

The oral tyrosine kinase inhibitor was approved for use in adults in all phases of the disease — chronic, accelerated, or myeloid or lymphoid blast phases — who had resistance or tolerance to previous treatments, including imatinib mesylate (Gleevec).

The drug originally received accelerated approval under subpart H of the Food, Drug, and Cosmetic Act in June 2006 on the basis of phase I and II trial data after the FDA’s Oncologic Drugs Advisory Committee unanimously recommended approval. (See FDA Okays Sprycel for CML Resistant or Intolerant to Gleevec)

At that time, it was also approved for Philadelphia chromosome-positive acute lymphoblastic leukemia.

The full approval was made, in part, on the basis of results from a phase 3 randomized, dose-optimization trial that included 670 patients with chronic-phase CML. The study is scheduled for presentation at the annual meeting of the American Society of Clinical Oncology in Orlando.

Of the 167 patients who received the recommended starting dose of 100 mg daily, 63% met the primary endpoint — a major cytogenic response.

Of those who had a response, 93% sustained it through 18 months.

In addition, overall survival and progression-free survival were 91% and 80%, respectively, at the two-year follow-up.

In seven clinical trials, the most common serious adverse events were pleural effusion (11%), gastrointestinal bleeding (4%), febrile neutropenia (4%), dyspnea (3%), pneumonia (3%), pyrexia (3%), diarrhea (3%), infection (2%), congestive heart failure/cardiac dysfunction (2%), pericardial effusion (1%), and central nervous system hemorrhage (1%).

The most frequently reported adverse reactions of any severity were myelosuppression, fluid retention events, diarrhea, headache, dyspnea, skin rash, fatigue, nausea, and hemorrhage.

Grade 3/4 laboratory abnormalities in patients who received 100 mg of dasatinib daily included neutropenia (36%), thrombocytopenia (23%), anemia (13%), hypophosphatemia (10%) and hypokalemia (2%).

Discontinuation related to adverse events occurred in 15% of patients in chronic phase, 16% in accelerated phase, 15% in myeloid blast phase, and 8% in lymphoid blast phase CML, as well as in 8% of patients with Philadelphia chromosome-positive acute lymphoblastic leukemia.

The recommended daily doses of dasatinib are 100 mg for patients in chronic-phase CML and 140 mg for those in all other phases.

Related Article(s):

• ASCO: Dasatinib (Sprycel) Works as First-Line Therapy for Chronic Myelogenous Leukemia
• AACR: Agent Shows Value in Gleevec-Resistant CML
  
• FDA Okays Sprycel for CML Resistant or Intolerant to Gleevec

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