FDA/CDC

FDA updates nilotinib product label outlining criteria for discontinuation


 

The Food and Drug Administration has updated the label of nilotinib (Tasigna) with information on how to discontinue use of the drug for patients who meet certain criteria. Nilotinib, a kinase inhibitor that blocks the BCR-ABL protein that promotes abnormal cell growth, was originally approved in 2007 and was indicated for use in patients with Philadelphia chromosome positive (Ph+) chronic myeloid leukemia (CML). In accordance with the new label update, patients who have early phase CML, have been using nilotinib for 3 years or more, and whose leukemia has responded to treatment according to a test that has received FDA marketing authorization, may be eligible to discontinue use of nilotinib.

The information that led to the FDA approved label update was based on two single-arm trials of patients with chronic phase Ph+ CML. The trial measured the length of time patients were able to discontinue use of nilotinib without leukemia returning, and who had entered treatment-free remission (TFR). In the first trial, among 190 newly diagnosed CML patients who discontinued taking nilotinib after using the drug for 3 or more years, 51.6% were still in TFR after about 1 year (48 weeks) and 48.9% were still in TFR after nearly 2 years (96 weeks). Similar results were seen in the second trial, among 126 patients, with 57.9% in TFR after about a year (48 weeks) and 53.2% in TFR after approximately 2 years (96 weeks).

An important element of these trials was regular monitoring of specific RNA information that specifies the level of BCR-ABL protein in the blood using a diagnostic test that has received FDA marketing authorization. Monitoring with a test that accurately detects the reductions of RNA information in the blood with accuracy and precision is critical in discontinuing the use of nilotinib. This monitoring will allow physicians to detect the first signs of relapse.

“Patients diagnosed with CML generally face a lifetime of treatment to keep their leukemia from growing or recurring,” said Richard Pazdur, MD, acting director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research. “Today’s approval shows that some patients may be able to stop treatment with Tasigna altogether if they are showing a strong response to therapy. While we welcome this progress in patient care, it’s important to note that any discontinuation of treatment still means patients must be regularly monitored for disease recurrence,” Dr. Pazdur said in the FDA statement.

Common side effects after discontinuing use of nilotinib include body aches and pain in the bones and extremities. Severe side effects of taking nilotinib can include myelosuppression, blockages in the heart and arteries, and inflammation of the pancreas. Severe liver damage can also occur.

Severe side effects typically associated with nilotinib administration occurred less frequently in patients who discontinued the drug. However, the long-term outcomes of patients discontinuing versus continuing treatment are unknown at this time, the FDA noted.

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