Tasigna only treatment to surpass Gleevec in slowing disease progression for newly diagnosed CML patients data to be presented at 46th Annual ASCO meeting www.novartis.com www.asco.org
Longer-term, 18-month, data from a pivotal study being presented at the 46th Annual Meeting of the American Society for Clinical Oncology (ASCO), shows that Tasigna (nilotinib) 200 mg capsules continues to demonstrate superiority to the standard of care, Gleevec, as a first-line treatment in patients with Philadelphia chromosome-positive Chronic Myeloid Leukemia (Ph+ CML).
CML is a disease in which the body produces cancerous white blood cells and is responsible for 10 to 15 percent of all adult cases of leukemia. In 2009 alone, there were more than 5,000 newly diagnosed cases of CML in the United States.
In 2001, Gleevec (imatinib mesylate) tablets* revolutionized the treatment of Ph+ CML, becoming the gold standard of care by demonstrating the highest overall survival rate observed for people with this type of cancer.
The longest-term comparative study of a second-generation tyrosine kinase inhibitor to date Tasigna induced more than twice the major molecular response (MMR) rate compared with Gleevec and resulted in significantly lower rates of progression to advanced disease. Findings based on preliminary data, which will need to be confirmed by longer-term follow-up, also indicated that the drug positively impacted patient survival outcomes. Analysis of event-free survival, progression-free survival and overall survival showed significant differences between Tasigna and Gleevec, in favor of Tasigna.
Dr. Stuart L. Goldberg, Chief of the Division of Leukemia, John Theurer Cancer Center, Hackensack University Medical Center, Hackensack, NJ.
About Tasigna3
Tasigna (nilotinib) is indicated for the treatment of newly diagnosed adult patients with Philadelphia chromosomepositive chronic myelogenous leukemia (Ph+ CML) in chronic phase and the treatment of chronic phase (CP) and accelerated phase (AP) Ph+ CML in adult patients resistant or intolerant to prior therapy that included imatinib. The effectiveness of Tasigna is based on hematologic and cytogenetic response rates. There are no controlled trials demonstrating a clinical benefit, such as improvement in disease-related symptoms or increased survival.
Tasigna important safety information
WARNING: QT PROLONGATION and SUDDEN DEATHS
Tasigna prolongs the QT interval. Sudden deaths have been reported in patients receiving nilotinib. Tasigna should not be used in patients with hypokalemia, hypomagnesemia, or long QT syndrome. Hypokalemia or hypomagnesemia must be corrected prior to Tasigna administration and should be periodically monitored. Drugs known to prolong the QT interval and strong CYP3A4 inhibitors should be avoided. Patients should avoid food 2 hours before and 1 hour after taking dose. A dose reduction is recommended in patients with hepatic impairment. ECGs should be obtained to monitor the QTc at baseline, seven days after initiation, and periodically thereafter, as well as following any dose adjustments.
Contraindications
Do not use in patients with hypokalemia, hypomagnesemia, or long QT syndrome.
Warnings and precautions
Myelosuppression
Treatment with Tasigna can cause Grade 3/4 thrombocytopenia, neutropenia and anemia. Occurrence is more frequent in patients with imatinib-resistant or -intolerant CML, in particular in patients with CML-AP. Complete blood counts should be performed every two weeks for the first 2 months and then monthly thereafter, or as clinically indicated. Myelosuppression was generally reversible and usually managed by withholding Tasigna temporarily or dose reduction.
QT Prolongation
Tasigna prolongs the QT interval. ECGs should be performed at baseline, seven days after initiation, periodically as clinically indicated and following dose adjustments. Correct hypokalemia or hypomagnesemia prior to administration and monitor periodically.
Significant prolongation of the QT interval may occur when Tasigna is inappropriately taken with food, and/or strong CYP3A4 inhibitors and/or medicinal products with a known potential to prolong QT. Therefore, co-administration with food must be avoided and concomitant use with strong CYP3A4 inhibitors and/or medicinal products with a known potential to prolong QT should be avoided. The presence of hypokalemia and hypomagnesemia may further enhance this effect.
Sudden Deaths
There were sudden deaths reported in the safety population and in the expanded access program. Ventricular repolarization abnormalities may have contributed to their occurrence. No cases of sudden death have been reported in the newly diagnosed Ph+ CML-CP Phase III study.
Elevated Serum Lipase
Caution is recommended in patients with a history of pancreatitis. Check serum lipase levels monthly or as clinically indicated. In case lipase elevations are accompanied by abdominal symptoms, doses should be interrupted and appropriate diagnostics should be considered in order to exclude pancreatitis.
Hepatoxicity
Serum bilirubin and hepatic transaminases
The use of Tasigna may result in elevations in bilirubin, AST/ALT, and alkaline phosphatase. Hepatic function tests should be checked monthly or as clinically indicated.
Electrolyte Abnormalities
Tasigna can cause hypophosphatemia, hypokalemia, hyperkalemia, hypocalcemia, and hyponatremia. Correct electrolyte abnormalities prior to initiating Tasigna and monitor periodically during therapy.
Hepatic Impairment
Nilotinib exposure is increased in patients with impaired hepatic function. A lower starting dose is recommended for patients with mild to severe hepatic impairment and QT interval should be monitored closely.
Drug Interactions
The concomitant use of QT prolonging drugs and strong inhibitors or inducers of CYP3A4 should be avoided as they may affect serum concentration of Tasigna.
Concomitant strong CYP3A4 inhibitors
The concomitant use of strong CYP3A4 inhibitors or anti-arrhythmic drugs (including, but not limited to amiodarone, disopyramide, procainamide, quinidine and sotalol) and other drugs that may prolong QT interval (including, but not limited to chloroquine, clarithromycin, haloperidol, methadone, moxifloxacin, and pimozide) should be avoided. Should treatment with any of these agents be required, it is recommended that therapy with Tasigna be interrupted. If interruption of treatment with Tasigna is not possible, patients who require treatment with a drug that prolongs QT or strongly inhibits CYP3A4 should be closely monitored for prolongation of the QT interval, and a dose reduction to the daily dose is recommended (400 mg once daily). If the strong inhibitor is discontinued, a washout period should be allowed before Tasigna is adjusted upward to the indicated dose. Close monitoring for prolongation of the QT interval is indicated for patients who cannot avoid strong CYP3A4 inhibitors. Grapefruit products and other foods that are known to inhibit CYP3A4 should also be avoided.
Concomitant strong CYP3A4 inducers
The concomitant use of strong CYP3A4 inducers should be avoided (including, but not limited to, dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin, rifapentin, phenobarbital). Patients should also refrain from taking St Johns Wort. If patients must be co-administered a strong CYP3A4 inducer, the dose of Tasigna may need to be increased, depending on patient tolerability. If the strong inducer is discontinued, the Tasigna dose should be reduced to the indicated dose. Tasigna is a competitive inhibitor of CYP3A4, CYP2C8, CYP2C9, CYP2D6, and UGT1A1.
