The FDA recently updated the product label for nilotinib to include information for providers about how to discontinue the drug in certain patients. Nilotinib, first approved by the FDA in 2007, is indicated for the treatment of patients with Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML).
With these updated dosing recommendations, patients with chronic phase CML who have been taking nilotinib for 3 years or more, and whose leukemia has responded to treatment according to specific criteria as detected by a test that has received FDA marketing authorization, may be eligible to stop taking nilotinib.
"Patients diagnosed with CML generally face a lifetime of treatment to keep their leukemia from growing or recurring," said Richard Pazdur, MD, Director of the FDA's Oncology Center of Excellence and Acting Director of the Office of Hematology and Oncology Products in the FDA's Center for Drug Evaluation and Research. "[This] approval shows that some patients may be able to stop treatment with nilotinib 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."
Nilotinib is a kinase inhibitor that works in CML by blocking the protein BCR-ABL, which promotes abnormal cell growth. The FDA's action adds information to the product label for patients and health care providers regarding the conditions under which patients may be eligible to discontinue treatment and notes that if treatment is stopped patients must be regularly monitored for disease recurrence.
The information about discontinuing nilotinib was based on two single-arm trials of patients with Ph+ chronic phase CML. The trials measured how long patients were able to stop taking nilotinib without the leukemia returning (treatment-free remission, or TFR). In both trials, patients had to meet rigorous criteria showing how their cancer had responded to treatment before stopping nilotinib. In the first trial, among the 190 newly diagnosed patients with CML who stopped nilotinib after taking it for 3 or more years and meeting other specified criteria, 51.6 percent were still in the TFR phase after approximately 1 year (48 weeks) and 48.9 percent were still in the TFR phase after approximately 2 years (96 weeks). In the second trial, among the 126 patients who had stopped nilotinib after taking it for 3 or more years after switching from the cancer drug imatinib, 57.9 percent were still in the TFR phase after approximately 1 year (48 weeks) and 53.2 percent were still in the TFR phase after approximately 2 years (96 weeks).
An important part of both trials was regular and frequent monitoring of specific genetic (RNA) information that specifies the BCR-ABL protein level in the blood with a diagnostic test that has received FDA marketing authorization. Monitoring with a test able to detect reductions of specific RNA information with high accuracy and precision is critical to the safe discontinuation of nilotinib, as this monitoring provides the first signs of relapse.
Common side effects in patients who discontinued nilotinib include musculoskeletal symptoms such as body aches, bone pain, and pain in extremities. Some patients experienced prolonged musculoskeletal symptoms.
The update to the nilotinib labeling information was granted Priority Review. Nilotinib also received Orphan Drug designation, which provides incentives to assist and encourage the development of drugs for rare diseases.