Table 2.
Adverse Events With Special Focus on the Most Frequent Ones (Safety Population)
| Event | L+T (n = 2,061) | T→L (n = 2,076) | L (n = 2,057) | T (n = 2,076) |
|---|---|---|---|---|
| Adverse event, No. (%) | ||||
| Patients with at least one grade 3-4 event | 944 (46) | 666 (32) | 840 (41) | 512 (25) |
| Patients with at least one serious adverse event | 430 (21) | 352 (17) | 431 (21) | 292 (14) |
| Fatal adverse events | 9 (< 1) | 14 (< 1) | 15 (< 1) | 9 (< 1) |
| Treatment withdrawals for toxicity | 482 (23) | 262 (13) | 314 (15) | 169 (8) |
| Cardiac events, No. (%) | ||||
| Symptomatic CHF, including severe CHF (NYHA class II, III, IV) | 68 (3) | 37 (2) | 37 (2) | 53 (3) |
| Severe CHF (NYHA class III, IV) | 22 (1) | 4 (< 1) | 6 (< 1) | 18 (1) |
| LVEF ≥ 10 decrease and ≥ LLN (based on worst case on therapy) | 456 (23) | 330 (17) | 366 (19) | 403 (20) |
| LVEF ≥ 10 decrease and < LLN (based on worst case on therapy) | 103 (5) | 57 (3) | 63 (3) | 97 (5) |
| Primary cardiac end point | 20 (< 1) | 5 (< 1) | 7 (< 1) | 18 (< 1) |
| Any cardiac end point | 77 (4) | 50 (2) | 39 (2) | 94 (5) |
| Adverse events of special interest | ||||
| Diarrhea grade 3-4 | 315 (15) | 100 (5) | 233 (11) | 27 (1) |
| Rash/skin toxicity grade 3-4 | 100 (5) | 80 (4) | 126 (6) | 12 (1) |
| Hepatobiliary grade 3-4 | 71 (3) | 54 (3) | 90 (4) | 16 (1) |
Abbreviations: L+T, lapatinib plus trastuzumab; T→L, trastuzumab followed by lapatinib; L, lapatinib; T, trastuzumab; CHF, congestive heart failure; NYHA, New York Heart Association; LVEF, left ventricular ejection fraction; LLN, lower limit of normal.