Table 3.
Adverse events and cardiac monitoring over the two 6-month periods
|
12-month group |
6-month group |
||||||
|---|---|---|---|---|---|---|---|
| Total | Months 1–6 | Months 7–12 | Total | Months 1–6 | Months 7–12 | ||
| Adverse event with severe* CTCAE grade | 459/1894 (24%) | 350/1894 (18%) | 259/1764 (15%) | 373/1939 (19%) | 370/1939 (19%) | 8/93 (9%) | |
| Serious adverse reaction to trastuzumab† | 64/2044 (3%) | 39/2044 (2%) | 25/2019‡ (1%) | 29/2041 (1%) | 28/2041 (1%) | 2/2015‡ (0·1%) | |
| Clinical cardiac dysfunction§ | 224/1968 (11%) | 164/1968 (8%) | 157/1936 (8%) | 155/1994 (8%) | 126/1994 (6%) | 96/1894 (5%) | |
| Stopped trastuzumab permanently due to cardiac toxicity | 146/1894 (8%) | 63/1894 (3%) | 83/1764 (5%) | 61/1939 (3%) | 60/1939 (3%) | 1/93 (1%) | |
| Cardiac death¶ | 7/2044 (<1%) | 0/2044 | 0/2019‡ | 4/2041 (<1%) | 0/2041 | 0/2015‡ | |
| Cardiac death related to trastuzumab¶ | 0/2044 | 0/2044 | 0/2019‡ | 0/2041 | 0/2041 | 0/2015‡ | |
| Low LVEF‖ | 228/2040 (11%) | 148/2040 (7%) | 151/1938 (8%) | 176/2038 (9%) | 146/2038 (7%) | 84/1749 (5%) | |
| Substantial falls in LVEF | |||||||
| Absolute decrease of ≥10% from baseline to <50% | 163/1959 (8%) | 98/1950 (5%) | 102/1873 (5%) | 132/1959 (7%) | 102/1954 (5%) | 60/1693 (4%) | |
| LVEF <50% after a baseline of ≥59% | 108/1959 (6%) | 63/1950 (3%) | 71/1873 (4%) | 86/1959 (4%) | 70/1954 (4%) | 32/1693 (2%) | |
Data are n/N (%). CTCAE=Common Terminology Criteria for Adverse Events. LVEF=left ventricular ejection fraction.
CTCAE grade of 3 or more, or grade of 2 for palpitations.
Denominators exclude the three patients known not to have received trastuzumab.
Denominators reduced because of either deaths or withdrawal of consent for follow-up within the first 6 months.
Clinical cardiac dysfunction is defined as symptoms of cardiac disease, signs of congestive heart failure, use of new medication for cardiac disease, or a combination of these factors.
11 deaths were reported to have a cardiac cause, either first cause or contributory; none occurred during the first 12 months after starting trastuzumab treatment; nine patients died without metastatic disease and two had metastatic disease; in all cases, trastuzumab was considered unrelated or unlikely to be related with the cardiac problems.
Low LVEF was defined as ejection fraction of less than 50% or unknown ejection fraction but classified on report as not normal.