Table 5.
TEAE (any grade) resulting in dose delay or dose reduction (in ≥5% of patients in any arm), and treatment discontinuation (in ≥2% of patients in any arm)a
| Asia region safety population | Overall safety population | |||||||
|---|---|---|---|---|---|---|---|---|
| Combination therapy | Monotherapy | Combination therapy | Monotherapy | |||||
|
nal‐IRI+ 5‐FU/LV n = 33 |
5‐FU/LV n = 29 |
nal‐IRI n = 50 |
5‐FU/LV n = 42 |
nal‐IRI+ 5‐FU/LV n = 117 |
5‐FU/LV n = 105 |
nal‐IRI n = 147 |
5‐FU/LV n = 134 |
|
| Patients with TEAE leading to any dose modification, n (%) | 28 (84.8) | 8 (27.6) | 30 (60.0) | 12 (28.6) | 83 (70.9) | 37 (35.2) | 81 (55.1) | 48 (35.8) |
| Dose delayb | 28 (84.8) | 8 (27.6) | 21 (42.0) | 12 (28.6) | 72 (61.5) | 33 (31.4) | 49 (33.3) | 43 (32.1) |
| Dose reductionc | 16 (48.5) | 1 (3.4) | 21 (42.0) | 2 (4.8) | 39 (33.3) | 4 (3.8) | 46 (31.3) | 5 (3.7) |
| Treatment discontinuation | 4 (12.1) | 0 | 5 (10.0) | 0 | 13 (11.1) | 7 (6.7) | 17 (11.6) | 10 (7.5) |
| Dose delay, n (%) | ||||||||
| Neutropenia | 16 (48.5)d | 1 (3.4) | 9 (18.0)d | 1 (2.4)d | 30 (25.6)e | 5 (4.8) | 13 (8.8)e | 5 (3.7)e |
| WBC count decreased | 11 (33.3) | 0 | 1 (2.0) | 0 | 14 (12.0) | 1 (1.0) | 1 (0.7) | 1 (0.7) |
| Asthenia | 3 (9.1) | 2 (6.9) | 2 (4.0) | 3 (7.1) | 5 (4.3) | 2 (1.9) | 4 (2.7) | 3 (2.2) |
| Leukopenia | 3 (9.1) | 0 | 1 (2.0) | 0 | 7 (6.0) | 1 (1.0) | 1 (0.7) | 1 (0.7) |
| Febrile neutropenia | 2 (6.1) | 0 | 1 (2.0) | 0 | 3 (2.6) | 0 | 2 (1.4) | 0 |
| Platelet count decreased | 2 (6.1) | 0 | 0 | 0 | 6 (5.1) | 0 | 1 (0.7) | 1 (0.7) |
| Vomiting | 2 (6.1) | 0 | 0 | 1 (2.4) | 7 (6.0) | 2 (1.9) | 4 (2.7) | 3 (2.2) |
| Diarrhea | 1 (3.0) | 1 (3.4) | 1 (2.0) | 1 (2.4) | 9 (7.7) | 4 (3.8) | 8 (5.4) | 4 (3.0) |
| Fatigue | 0 | 0 | 1 (2.0) | 1 (2.4) | 8 (6.8) | 0 | 3 (2.0) | 1 (0.7) |
| Tumor‐associated fever | 0 | 2 (6.9) | 0 | 2 (4.8) | 0 | 2 (1.9) | 0 | 2 (1.5) |
| Dose reduction, n (%) | ||||||||
| Neutropenia | 12 (36.4)d | 0 | 12 (24.0)d | 0d | 21 (17.9)e | 0 | 14 (9.5)e | 0e |
| WBC count decreased | 5 (15.2) | 0 | 3 (6.0) | 0 | 6 (5.1) | 0 | 3 (2.0) | 0 |
| Anemia | 4 (12.1) | 0 | 4 (8.0) | 0 | 4 (3.4) | 0 | 6 (4.1) | 0 |
| Vomiting | 1 (3.0) | 0 | 4 (8.0) | 0 | 2 (1.7) | 0 | 9 (6.1) | 0 |
| Diarrhea | 0 | 0 | 3 (6.0) | 0 | 7 (6.0) | 0 | 17 (11.6) | 0 |
| Febrile neutropenia | 0 | 0 | 4 (8.0) | 0 | 1 (0.9) | 0 | 5 (3.4) | 0 |
| Treatment discontinuation, n (%) | ||||||||
| Ascites | 1 (3.0) | 0 | 0 | 0 | 2 (1.7) | 0 | 0 | 0 |
| Biliary tract infection | 1 (3.0) | 0 | 0 | 0 | 1 (0.9) | 0 | 0 | 0 |
| Neutropenia | 1 (3.0)f | 0 | 1 (2.0)f | 0f | 2 (1.7)e | 1 (1.0)e | 2 (1.4)e | 1 (0.7)e |
| Pneumonia | 1 (3.0) | 0 | 0 | 0 | 1 (0.9) | 0 | 0 | 0 |
| Sepsis | 1 (3.0) | 0 | 0 | 0 | 2 (1.7) | 1 (1.0) | 1 (0.7) | 1 (0.7) |
| Septic shock | 1 (3.0) | 0 | 0 | 0 | 1 (0.9) | 0 | 0 | 0 |
| Cholangitis suppurative | 0 | 0 | 1 (2.0) | 0 | 0 | 0 | 1 (0.7) | 0 |
| Diarrhea | 0 | 0 | 0 | 0 | 2 (1.7) | 0 | 3 (2.0) | 0 |
| Enterocolitis infectious | 0 | 0 | 1 (2.0) | 0 | 0 | 0 | 1 (0.7) | 0 |
| Jaundice cholestatic | 0 | 0 | 1 (2.0) | 0 | 0 | 0 | 1 (0.7) | 0 |
| Leukopenia | 0 | 0 | 1 (2.0) | 0 | 1 (0.9) | 0 | 1 (0.7) | 0 |
| Respiratory failure | 0 | 0 | 1 (2.0) | 0 | 0 | 0 | 1 (0.7) | 0 |
| Vomiting | 0 | 0 | 0 | 0 | 2 (1.7) | 0 | 3 (2.0) | 1 (0.7) |
| Patients with any TEAE related to study drug leading to death (all causes), n (%) | 1 (3.0)g | 0 | 2 (4.0)h | 0 | 1 (0.9)g | 0 | 4 (2.7)h | 0 |
Abbreviations: 5‐FU, 5‐fluorouracil; LV, leucovorin (folinic acid); nal‐IRI, liposomal irinotecan; WBC, white blood cell.
Patients with multiple occurrences are counted only once in any category. Safety population included patients who received at least one dose of study drug. Adverse events coded using MedDRA version 14.1. Treatment emergent adverse events (TEAE) are events that occurred or worsened on or after the day of first dose of the study drug and within 30 d after last administration of study drug.
TEAE with action taken as: dose not given or infusion interrupted.
TEAE with action taken as: dose decreased or slowing infusion rate.
Summary term comprising neutropenia, neutrophil count decreased, and febrile neutropenia.
Summary term comprising agranulocytosis, decreased neutrophil count, febrile neutropenia, granulocytopenia, neutropenia, neutropenic sepsis, and pancytopenia.
Summary term comprising neutrophil count decreased and neutropenia.
Causes of death: Septic shock on study day 11, n = 1.
Causes of death: Disseminated intravascular coagulation and pulmonary embolism on study day 12 (n = 1), gastrointestinal syndrome on study day 30 (n = 1), septic shock on study day 101 (n = 1), and infectious colitis on study day 206 (n = 1).