t especially those with prior anthracycline and cyclophosphamide (AC) exposure, should undergo baseline cardiac assessment including history and physical examination, ECG, echocardiogram, or MUGA scan or magnetic resonance imaging. A careful risk-benefit assessment should be made before deciding to treat with Herceptin.
Herceptin and anthracyclines should not be used currently in combination except in a well-controlled clinical trial setting with cardiac monitoring. Patients who have previously received anthracyclines are also at risk of cardiotoxicity with Herceptin treatment, although the risk is lower than with concurrent use of Herceptin and anthracyclines. Because the half-life of Herceptin is approximately 4-5 weeks Herceptin may persist in the circulation for up to 20-25 weeks after stopping Herceptin treatment. Patients who receive anthracyclines after stopping Herceptin may possibly be at increased risk of cardiotoxicity. If possible, physicians should avoid anthracycline-based therapy for up to 25 weeks after stopping Herceptin. If anthracyclines are used, the patient's cardiac function should be monitored carefully.
In patients with EBC an increase in the incidence of symptomatic and asymptomatic cardiac events was observed when Herceptin was administered after anthracycline-containing chemotherapy compared to administration with a non-anthracycline regimen of docetaxel and carboplatin and was more marked when Herceptin was administered concurrently with taxanes than when administered sequentially to taxanes. Regardless of the regimen used, most symptomatic cardiac events occurred within the first 18 months. In one of the 3 pivotal studies conducted in which a median follow-up of 5.5 years was available (BCIRG006) a continuous increase in the cumulative rate of symptomatic cardiac or LVEF events was observed in patients who were administered Herceptin concurrently with a taxane following anthracycline therapy up to 2.37% compared to approximately 1% in the two comparator arms (anthracycline plus cyclophosphamide followed by taxane and taxane, carboplatin and Herceptin).
In EBC, the following patients were excluded from the HERA trial, there are no data about the benefit-risk balance, and therefore treatment can not be recommended in such patients:
• History of documented congestive heart failure
• High-risk uncontrolled arrhythmias
• Angina pectoris requiring a medicinal product
• Clinically significant valvular disease
• Evidence of transmural infarction on ECG
• Poorly controlled hypertension
Formal cardiological assessment should be considered in patients in whom there are cardiovascular concerns following baseline screening. Cardiac function should be further monitored during treatment (e.g. every 12 weeks). Monitoring may help to identify patients who develop cardiac dysfunction. For early breast cancer patients, cardiac assessment, as performed at baseline, should be repeated every 3 months during treatment and every 6 months following discontinuation of treatment until 24 months from the last administration. In patients who receive anthracycline containing chemotherapy further monitoring is recommended, and should occur yearly up to 5 years from the last administration, or longer if a continuous decrease of LVEF is observed. Patients who develop asymptomatic cardiac dysfunction may benefit from more frequent monitoring (e.g. every 6 |
