Table 2.
Worst Grade of Adverse Events
| Event | Treatment |
||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Letrozole (n = 2,448) |
Tamoxifen (n = 2,447)* |
P | |||||||||||||
| Grade |
Grade |
||||||||||||||
| 1 No. | 2 No. | 3 No. | 4 No. | 5 No. | Overall |
1 No. | 2 No. | 3 No. | 4 No. | 5 No. | Overall |
||||
| No. | % | No. | % | ||||||||||||
| CVA/TIA | 0 | 0 | 13 | 25 | 7 | 45 | 1.8 | 0 | 0 | 7 | 28 | 3 | 38 | 1.6 | .51 |
| Thromboembolic event | 5 | 27 | 16 | 10 | 5 | 63 | 2.6 | 3 | 48 | 31 | 18 | 4 | 104 | 4.3 | .001 |
| Cardiac event† | 52 | 24 | 60 | 23 | 10 | 169 | 6.9 | 73 | 28 | 34 | 10 | 7 | 152 | 6.2 | .36 |
| Ischemic heart disease | 12 | 9 | 25 | 18 | 5 | 69 | 2.8 | 13 | 11 | 15 | 8 | 2 | 49 | 2.0 | .08 |
| Cardiac failure‡ | 6 | 3 | 14 | 2 | 5 | 30 | 1.2 | 10 | 3 | 6 | 2 | 4 | 25 | 1.0 | .59 |
| Other cardiovascular event‡ | 6 | 15 | 3 | 0 | 0 | 24 | 1.0 | 10 | 2 | 1 | 0 | 0 | 13 | 0.5 | .10 |
| Hypertension‡ | 53 | 36 | 41 | 2 | 0 | 132 | 5.4 | 62 | 27 | 39 | 2 | 0 | 130 | 5.3 | .95 |
| Hypotension‡ | 11 | 2 | 1 | 0 | 0 | 14 | 0.6 | 3 | 4 | 2 | 0 | 0 | 9 | 0.4 | .40 |
| Hypercholesterolemia | 1021 | 259 | 11 | 0 | 0 | 1291 | 52.7 | 564 | 63 | 4 | 2 | 0 | 633 | 25.9 | < .001 |
| Vaginal bleeding | 89 | 14 | 1 | 0 | 0 | 104 | 4.2 | 167 | 49 | 6 | 0 | 0 | 222 | 9.1 | < .001 |
| Vaginal dryness‡ | 44 | 42 | 2 | 0 | 0 | 88 | 3.6 | 27 | 10 | 0 | 0 | 0 | 37 | 1.5 | < .001 |
| Nausea | 183 | 69 | 6 | 0 | 0 | 258 | 10.5 | 195 | 39 | 8 | 0 | 0 | 242 | 9.9 | .48 |
| Vomiting | 50 | 29 | 3 | 0 | 0 | 82 | 3.3 | 62 | 11 | 5 | 0 | 0 | 78 | 3.2 | .81 |
| Hot flushes | 408 | 412 | 0 | 0 | 0 | 820 | 33.5 | 426 | 499 | 0 | 0 | 0 | 925 | 37.8 | .002 |
| Night sweating | 186 | 168 | 0 | 0 | 0 | 354 | 14.5 | 195 | 223 | 0 | 0 | 0 | 418 | 17.1 | .01 |
| Bone fractures | 0 | 160 | 84 | 0 | 0 | 244 | 10.0 | 0 | 122 | 43 | 0 | 0 | 165 | 6.7 | < .001 |
| Osteoporosis‡ | 35 | 79 | 10 | 0 | 0 | 124 | 5.1 | 20 | 29 | 5 | 0 | 0 | 54 | 2.2 | < .001 |
| Arthralgia‡ | 304 | 197 | 48 | 2 | 0 | 551 | 22.5 | 244 | 131 | 31 | 0 | 0 | 406 | 16.6 | < .001 |
| Myalgia‡ | 136 | 53 | 16 | 1 | 0 | 206 | 8.4 | 120 | 39 | 13 | 0 | 0 | 172 | 7.0 | .08 |
| Carpal tunnel‡ | 7 | 7 | 6 | 0 | 0 | 20 | 0.8 | 3 | 1 | 1 | 0 | 0 | 5 | 0.2 | .004 |
| Nausea and vomiting | 196 | 78 | 6 | 0 | 0 | 280 | 11.4 | 210 | 45 | 8 | 0 | 0 | 263 | 10.7 | .47 |
| Hot flushes and night sweating | 455 | 447 | 0 | 0 | 0 | 902 | 36.8 | 450 | 547 | 0 | 0 | 0 | 997 | 40.7 | .005 |
| Arthralgia and myalgia‡ | 379 | 230 | 58 | 2 | 0 | 669 | 27.3 | 309 | 159 | 40 | 0 | 0 | 508 | 20.8 | < .001 |
| Osteoporosis (grade 3) or bone fracture‡ | 0 | 157 | 93 | 0 | 0 | 250 | 10.2 | 0 | 121 | 46 | 0 | 0 | 167 | 6.8 | < .001 |
| Subjective nervous system/psychiatricठ| 234 | 144 | 33 | 2 | 0 | 413 | 16.9 | 200 | 132 | 34 | 0 | 0 | 366 | 15.0 | .07 |
NOTE. P values were derived by using Fisher's exact test and compared the incidence of grades 1 through 5 events between letrozole and tamoxifen.
Abbreviations: CVA, cerebrovascular accident; TIA, transient ischemic attack.
Prespecified adverse events were collected on case-report forms every 6 months while on trial treatment until 30 days after treatment completion and were graded according to the National Cancer Institute Common Toxicity Criteria, version 2.0, if available, and otherwise according to protocol-defined criteria. Nonspecified adverse events that were recorded as other were coded by an independent agency according to Medical Dictionary for Regulatory Activities without knowledge of treatment assignment. All cardiovascular adverse events were medically reviewed by the International Breast Cancer Study Group. Adverse events that occurred more than 30 days after selective crossover were collected but were excluded from this summary.
Cardiac events included ischemic cardiovascular disease, arrhythmia, heart failure, cardiopathy, valvular disease, ECG changes, sudden cardiac death, and cardiac not otherwise specified. It did not include hypertension or hypotension.
Not a prespecified adverse event; obtained from Medical Dictionary for Regulatory Activities coding of reported other adverse events.
Subjective nervous system/psychiatric adverse events were cognition disorders (eg, blackout, memory loss, impatience), perception disorders (eg, burning sensation, dysphasia, migraine), or other related disorders (eg, anxiety, melancholia, irritability, nightmares). Adverse events that were not included were nervous system disorders, such as CVA, TIA, Alzheimer's disease, Parkinson's disease, Bell's palsy, stenosis, diabetic coma, epilepsy/seizure, tremors, aneurism, cranial bleeding, sciatica, neuropathy; and psychiatric disorders, such as delirium and loss of libido.