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FDA Approves Label Update of Nilotinib, Enabling Certain Patients With CML to Stop Treatment After Sustained Response

Discontinuation in treatment marks a first in chronic myeloid leukemia

The FDA has updated the product label for the cancer drug nilotinib (Tasigna, Novartis) 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 early (chronic) phase CML who have been taking nilotinib for three 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 the drug.

CML is a cancer of the bone marrow and causes the body to make too many white blood cells. Almost all patients with CML have an abnormality known as the Philadelphia chromosome, which produces a protein called BCR-ABL. The National Cancer Institute estimates approximately 8,950 patients will be diagnosed with CML this year, and 1,080 will die of the disease.

Nilotinib is a kinase inhibitor that works in CML by blocking BCR-ABL, which promotes abnormal cell growth. This FDA update 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 three or more years and meeting other specified criteria, 51.6% were still in the TFR phase after approximately one year (48 weeks) and 48.9% were still in the TFR phase after approximately two years (96 weeks). In the second trial, among the 126 patients who had stopped nilotinib after taking it for three or more years after switching from the cancer drug imatinib, 57.9% were still in the TFR phase after approximately one year (48 weeks) and 53.2% were still in the TFR phase after approximately two 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 long-term outcomes of patients discontinuing versus continuing treatment are unknown at this time.

The update to the nilotinib labeling information was granted priority review, under which the FDA’s goal is to take action on an application within six months where the agency determines that the drug, if approved, would significantly improve the safety or effectiveness of treating, diagnosing or preventing a serious condition. Nilotinib also received orphan drug designation, which provides incentives to assist and encourage the development of drugs for rare diseases.

Source: FDA; December 22, 2017.



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