OGIVRI: Package Insert and Label Information (Page 4 of 10)
Metastatic Gastric Cancer
The data below are based on the exposure of 294 patients to trastuzumab in combination with a fluoropyrimidine (capecitabine or 5-FU) and cisplatin (Study 7). In the trastuzumab plus chemotherapy arm, the initial dose of trastuzumab 8 mg/kg was administered on Day 1 (prior to chemotherapy) followed by 6 mg/kg every 21 days until disease progression. Cisplatin was administered at 80 mg/m2 on Day 1 and the fluoropyrimidine was administered as either capecitabine 1000 mg/m2 orally twice a day on Days 1 to14 or 5-fluorouracil 800 mg/m2 /day as a continuous intravenous infusion Days 1 through 5. Chemotherapy was administered for six 21 day cycles. Median duration of trastuzumab treatment was 21 weeks; median number of trastuzumab infusions administered was eight.
| Body System/Adverse Event | Trastuzumab + FC (N = 294) N (%) | FC (N = 290) N (%) | ||
| All Grades | Grades 3/4 | All Grades | Grades 3/4 | |
| Investigations | ||||
| Neutropenia | 230 (78) | 101 (34) | 212 (73) | 83 (29) |
| Hypokalemia | 83 (28) | 28 (10) | 69 (24) | 16 (6) |
| Anemia | 81 (28) | 36 (12) | 61 (21) | 30 (10) |
| Thrombocytopenia | 47 (16) | 14 (5) | 33 (11) | 8 (3) |
| Blood and Lymphatic System Disorders | ||||
| Febrile Neutropenia | — | 15 (5) | — | 8 (3) |
| Gastrointestinal Disorders | ||||
| Diarrhea | 109 (37) | 27 (9) | 80 (28) | 11 (4) |
| Stomatitis | 72 (24) | 2 (1) | 43 (15) | 6 (2) |
| Dysphagia | 19 (6) | 7 (2) | 10 (3) | 1 (≤ 1) |
| Body as a Whole | ||||
| Fatigue | 102 (35) | 12 (4) | 82 (28) | 7 (2) |
| Fever | 54 (18) | 3 (1) | 36 (12) | 0 (0) |
| Mucosal Inflammation | 37 (13) | 6 (2) | 18 (6) | 2 (1) |
| Chills | 23 (8) | 1 (≤ 1) | 0 (0) | 0 (0) |
| Metabolism and Nutrition Disorders | ||||
| Weight Decrease | 69 (23) | 6 (2) | 40 (14) | 7 (2) |
| Infections and Infestations | ||||
| Upper Respiratory Tract Infections | 56 (19) | 0 (0) | 29 (10) | 0 (0) |
| Nasopharyngitis | 37 (13) | 0 (0) | 17 (6) | 0 (0) |
| Renal and Urinary Disorders | ||||
| Renal Failure and Impairment | 53 (18) | 8 (3) | 42 (15) | 5 (2) |
| Nervous System Disorders | ||||
| Dysgeusia | 28 (10) | 0 (0) | 14 (5) | 0 (0) |
The following subsections provide additional detail regarding adverse reactions observed in clinical trials of adjuvant breast cancer, metastatic breast cancer, metastatic gastric cancer, or post-marketing experience.
Cardiomyopathy
Serial measurement of cardiac function (LVEF) was obtained in clinical trials in the adjuvant treatment of breast cancer. In Study 3, the median duration of follow-up was 12.6 months (12.4 months in the observation arm; 12.6 months in the 1-year trastuzumab arm); and in Studies 1 and 2, 7.9 years in the AC-T arm, 8.3 years in the AC-TH arm. In Studies 1 and 2, 6% of all randomized patients with post-AC LVEF evaluation were not permitted to initiate trastuzumab following completion of AC chemotherapy due to cardiac dysfunction (LVEF < LLN or ≥ 16 point decline in LVEF from baseline to end of AC). Following initiation of trastuzumab therapy, the incidence of new-onset dose-limiting myocardial dysfunction was higher among patients receiving trastuzumab and paclitaxel as compared to those receiving paclitaxel alone in Studies 1 and 2, and in patients receiving one-year trastuzumab monotherapy compared to observation in Study 3 (see Table 6, Figures 1 and 2). The per-patient incidence of new-onset cardiac dysfunction, as measured by LVEF, remained similar when compared to the analysis performed at a median follow-up of 2.0 years in the AC-TH arm. This analysis also showed evidence of reversibility of left ventricular dysfunction, with 64.5% of patients who experienced symptomatic CHF in the AC-TH group being asymptomatic at latest follow-up, and 90.3% having full or partial LVEF recovery.
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LVEF <50% and Absolute Decrease from Baseline | Absolute LVEF Decrease | ||||
LVEF < 50% | ≥ 10% decrease | ≥ 16% decrease | < 20% and ≥ 10% | ≥ 20% | |
AC → TH (n = 1856) | 23.1% (428) | 18.5% (344) | 11.2% (208) | 37.9% (703) | 8.9% (166) |
AC → T (n = 1170) | 11.7% (137) | 7.0% (82) | 3.0% (35) | 22.1% (259) | 3.4% (40) |
Study 3§ | |||||
Trastuzumab (n = 1678) | 8.6% (144) | 7.0% (118) | 3.8% (64) | 22.4% (376) | 3.5% (59) |
Observation (n = 1708) | 2.7% (46) | 2.0% (35) | 1.2% (20) | 11.9% (204) | 1.2% (21) |
Study 4¶ | |||||
TCH (n = 1056) | 8.5% (90) | 5.9% (62) | 3.3% (35) | 34.5% (364) | 6.3% (67) |
AC → TH (n = 1068) | 17% (182) | 13.3% (142) | 9.8% (105) | 44.3% (473) | 13.2% (141) |
AC → T (n = 1050) | 9.5% (100) | 6.6% (69) | 3.3% (35) | 34% (357) | 5.5% (58) |
Time 0 is initiation of paclitaxel or trastuzumab + paclitaxel therapy.
Time 0 is the date of randomization.
Time 0 is the date of randomization.
The incidence of treatment emergent congestive heart failure among patients in the metastatic breast cancer trials was classified for severity using the New York Heart Association classification system (I−IV, where IV is the most severe level of cardiac failure) (see Table 2). In the metastatic breast cancer trials, the probability of cardiac dysfunction was highest in patients who received trastuzumab concurrently with anthracyclines.
In Study 7, 5.0% of patients in the trastuzumab plus chemotherapy arm compared to 1.1% of patients in the chemotherapy alone arm had LVEF value below 50% with a ≥ 10% absolute decrease in LVEF from pretreatment values.
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