rom clinical trials are available on re-treatment of patients with previous exposure to trastuzumab in the adjuvant setting.
Cardiac dysfunction
General considerations
Patients treated with KANJINTI are at increased risk for developing CHF (New York Heart Association [NYHA] class II-IV) or asymptomatic cardiac dysfunction. These events have been observed in patients receiving trastuzumab therapy alone or in combination with paclitaxel or docetaxel, particularly following anthracycline (doxorubicin or epirubicin) containing chemotherapy. These may be moderate to severe and have been associated with death (see section 4.8). In addition, caution should be exercised in treating patients with increased cardiac risk, e.g. hypertension, documented coronary artery disease, CHF, LVEF of < 55%, older age.
All candidates for treatment with KANJINTI, but especially those with prior anthracycline and cyclophosphamide (AC) exposure, should undergo baseline cardiac assessment including history and physical examination, electrocardiogram (ECG), echocardiogram, and/or multigated acquisition (MUGA) scan or magnetic resonance imaging. Monitoring may help to identify patients who develop cardiac dysfunction. Cardiac assessments, 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 of KANJINTI. A careful risk-benefit assessment should be made before deciding to treat with KANJINTI.
Trastuzumab may persist in the circulation for up to 7 months after stopping KANJINTI treatment based on population pharmacokinetic analysis of all available data (see section 5.2). Patients who receive anthracyclines after stopping KANJINTI may possibly be at increased risk of cardiac dysfunction. If possible, physicians should avoid anthracycline-based therapy for up to 7 months after stopping KANJINTI. If anthracyclines are used, the patient's cardiac function should be monitored carefully.
Formal cardiological assessment should be considered in patients in whom there are cardiovascular concerns following baseline screening. In all patients cardiac function should be monitored during treatment (e.g. every 12 weeks). Monitoring may help to identify patients who develop cardiac dysfunction. Patients who develop asymptomatic cardiac dysfunction may benefit from more frequent monitoring (e.g. every 6 - 8 weeks). If patients have a continued decrease in left ventricular function, but remain asymptomatic, the physician should consider discontinuing therapy if no clinical benefit of KANJINTI therapy has been seen.
The safety of continuation or resumption of trastuzumab in patients who experience cardiac dysfunction has not been prospectively studied. If LVEF percentage drops ≥ 10 points from baseline AND to below 50%, treatment should be suspended and a repeat LVEF assessment performed within approximately 3 weeks. If LVEF has not improved, or declined further, or symptomatic CHF has developed, discontinuation of KANJINTI should be strongly considered, unless the benefits for the individual patient are deemed to outweigh the risks. All such patients should be referred for assessment by a cardiologist and followed up.
If symptomatic cardiac failure develops during KANJINTI therapy, it should be treated with standard medicinal products for CHF. Most patients who developed CHF or asymptomatic cardiac dysfunction in piv |
