European Union Approves Nilotinib First-Line Therapy for Ph+ CML

Yael Waknine

January 03, 2011

January 3, 2011 — The European Commission has approved nilotinib (Tasigna; Novartis) for the first-line treatment of chronic-phase Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) in adults.

The European Commission's action was based on results from ENESTnd (Evaluating Nilotinib Efficacy and Safety in Clinical Trials of Newly Diagnosed Ph+ CML Patients), an ongoing phase 3 study comparing nilotinib and the current standard of care, imatinib (Gleevec; Novartis).

One-year data published in the New England Journal of Medicine (2010;362:2251-2259) revealed significantly greater major molecular response rates and complete cytogenetic response rates with nilotinib 600 mg/day than with imatinib 400 mg/day (44% vs 22% and 80% vs 65%, respectively; P < .001 for both comparisons).

Nilotinib also significantly delayed time to progression to accelerated phase or blast crisis relative to imatinib (= .01 and .004, respectively). These findings were supported by 18-month follow-up data presented at the 2010 American Society of Clinical Oncology annual meeting.

"We are pleased that [nilotinib] is now approved for newly diagnosed Ph+ CML patients in chronic phase in the member states of the European Union," said Hervé Hoppenot, president of Novartis Oncology, in a company news release. "With this expanded indication, newly diagnosed patients can benefit from a Bcr-Abl tyrosine kinase inhibitor that, according to pivotal data, surpassed the standard of care [imatinib] in key measures of efficacy, including delaying disease progression at 12 months."

The recommended dose of nilotinib for newly diagnosed chronic-phase Ph+ CML is 300 mg taken twice daily. A once-daily dose of 200 mg is recommended for patients requiring concomitant treatment with strong cytochrome P450 isoenzyme 3A4 (CYP 3A4) inhibitors; those with mild, moderate, or severe hepatic impairment should initially receive 200 mg of nilotinib twice daily.

Dose interruptions and adjustments are required for corrected QT (QTc) interval prolongation; neutropenia and thrombocytopenia; and severe elevations of serum lipase/amylase, bilirubin, or hepatic transaminase levels. The effects of nilotinib on QTc interval prolongation are increased by the coadministration of food, strong CYP 3A4 inhibitors, and other QTc-prolonging drugs.

As reported by Medscape Medical News, nilotinib previously was approved for this indication by the US Food and Drug Administration, Switzerland's Swissmedic, and Japan's Ministry of Health, Labor, and Welfare. Nilotinib also is licensed in more than 90 countries for the treatment of chronic- and accelerated-phase Ph+ CML in adult patients who are either resistant or intolerant to at least 1 previous therapy, including imatinib.

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