The US Food and Drug Administration (FDA) has updated labeling for nilotinib (Tasigna, Novartis) to include information concerning drug discontinuation.
Nilotinib received FDA approval in 2007 for the treatment of patients with Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML). Guidelines have recommended that most patients who achieve remission with tyrosine kinase inhibitor therapy continue taking the drugs indefinitely, yet it has been unclear whether continued therapy is necessary for all patients
The updated dosing recommendations now state that patients with chronic phase CML, who have been using nilotinib for 3 years or more and whose disease continues to respond according to specific criteria, may be eligible to stop their treatment.
“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, in an FDA news release.
“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,” Dr Pazdur explained. “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 an orally bioavailable aminopyrimidine-derivative Bcr-Abl tyrosine kinase inhibitor that was developed to overcome resistance to imatinib (Gleevec, Novartis). It binds to and stabilizes the inactive conformation of the kinase domain of the Abl protein of the Bcr-Abl fusion protein, thus inhibiting Bcr-Abl-mediated proliferation of Ph+ CML cells.
As reported previously by Medscape Medical News, a number of studies have looked at stopping or reducing the dose of tyrosine kinase inhibitors after long-term remission is achieved. The FDA’s decision to update labeling was based on the results of two single-group trials of patients with Ph+ chronic-phase CML who had stopped using nilotinib.
Both trials measured the length of time patients were able to maintain treatment-free remission without nilotinib. The first trial comprised a cohort of 190 newly diagnosed patients with CML who stopped therapy after 3 or more years of treatment. More than half (51.6%) remained in remission after 48 weeks, and 48.9% remained disease-free without treatment after almost 2 years (96 weeks).
The second trial, which included 126 patients who had stopped using nilotinib after taking it for 3 or more years and after they had switched from imatinib, 57.9% remained in remission at 48 weeks, and 53.2% also continued to be disease free after 96 weeks.
Common adverse effects observed in patients who discontinued nilotinib included musculoskeletal symptoms such as body aches, bone pain, and pain in extremities, with some reporting prolonged musculoskeletal symptoms. The FDA notes that the severe adverse effects typically associated with the agent occurred less frequently in patients who had discontinued it, but long-term outcomes of patients discontinuing vs continuing treatment are unknown at this time.
The update to the labeling information was granted priority review, and nilotinib also received orphan drug designation.
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