2010-06-18
In
collaboration with the Food and Drug Administration (FDA), and as a service to
our members, ASH provides information about newly approved therapies for patients.
This allows the agency to inform hematologists and professionals in
hematology-related fields of recent approvals in a timely manner. Included in
the message below is a link to the product label, which provides the relevant
clinical information on the indication, contraindications, dosing, and safety.
In providing this information, ASH does not endorse any product or therapy and
does not take any position on the safety or efficacy of the product or therapy
described. The following is a message from the FDA’s Office of Oncology Drug
Products.
On June 17, 2010, the U. S. Food and Drug Administration granted accelerated
approval to nilotinib (Tasigna® Capsules, Novartis Pharmaceuticals
Corporation), an orally administered kinase inhibitor, for the treatment of
adult patients with newly diagnosed Philadelphia chromosome positive chronic
myeloid leukemia (Ph+ CML) in chronic phase (CP-CML). The recommended nilotinib
dose for this indication is 300 mg orally twice daily. Tasigna® was
originally approved in October 2007 for the treatment of adult patients with
CP-CML and accelerated phase (AP-CML) resistant or intolerant to prior therapy
that included imatinib.
The efficacy and safety
of nilotinib in adults with newly diagnosed CP-CML was demonstrated in a single
randomized, active-control, open-label multinational clinical trial. Eight
hundred and forty-six patients were randomized to imatinib 400 mg QD (n = 283),
nilotinib 300 mg BID (n = 282), or nilotinib 400 mg BID (n = 281). The primary
objective was to compare the rate of major molecular response (MMR) at 12
months of nilotinib 300 mg BID and nilotinib 400 mg BID with that of imatinib
400 mg QD. MMR was defined as greater than or equal to 0.1%
BCR-ABL/ABL % by international scale measured by RQ-PCR, which corresponds to
a less than or equal to 3 log reduction of BCR-ABL transcript
from standardized baseline. The rate of complete cytogenetic response (CCyR) by
month 12 was the key secondary endpoint.
The primary efficacy
endpoint, MMR at 12 months, was achieved in 63 patients [22% (95% CI: 18, 28)]
in the imatinib arm, 125 patients [44% (95% CI: 38, 50)] in the nilotinib 300
mg BID arm, and 120 patients [43% (95% CI: 37, 49)] in the nilotinib 400 mg BID
arm. The differences were statistically significant (p is less
than 0.0001) for each nilotinib arm compared to the imatinib arm. CCyR
rates by 12 months were 65% (95% CI: 59, 71) for the imatinib arm, 80% (95% CI:
75, 85) for the nilotinib 300 mg BID arm, and 78% (95% CI: 73, 83) for the nilotinib
400 mg BID arm.
More than 98% of
patients in all three treatment arms experienced at least one adverse drug
reaction (ADR). Overall incidences of Grade 3-4 toxicity were 46% with
nilotinib 300 mg BID arm compared to 52% among patients treated with nilotinib
400 mg BID. Common ADRs reported more frequently on nilotinib treatment
compared to the imatinib treatment included rash, abnormalities of liver
function (AST, ALT, and bilirubin), hyperglycemia, hypercholesterolemia,
elevated serum lipase, and headache. The incidence and severity of
myelosuppression (e.g. neutropenia, anemia, and/or thrombocytopenia) appeared
similar in both imatinib and nilotinib. The most common electrolyte imbalances
in patients receiving nilotinib were hypophosphatemia, hypokalemia, and
hypocalcemia.
The safety profile of
the 300 mg BID dosing regimen appeared more favorable than 400 mg BID, while
the efficacy of the 300 mg BID dosing regimen appeared comparable to that of
400 mg BID. The recommended dose of nilotinib for patients with newly diagnosed
CP-CML is 300 mg BID.
Full prescribing
information is available at: http://www.accessdata.fda.gov/drugsatfda_docs/label/2010/022068s004s005lbl.pdf
Healthcare professionals should report all serious adverse events
suspected to be associated with the use of any medicine and device to FDA’s
MedWatch Reporting System by completing a form online at http://www.fda.gov/medwatch/report.htm,
by faxing (1-800-FDA-0178) or mailing the postage-paid address form provided
online, or by telephone (1-800-FDA-1088).
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