Table 3.
Overview of AEs (safety analysis set).
| All Grades | All patients (N = 3246) | CNS metastasis (n = 51) | Prior chemotherapy (n = 194) | ECOG PS 2 (n = 112) | VM + prior chemotherapy (n = 146) | VM + ECOG PS 2 (n = 77) |
|---|---|---|---|---|---|---|
| AEs, n (%) | 3203 (98.7) | 49 (96.1) | 186 (95.9) | 111 (99.1) | 138 (94.5) | 77 (100) |
| Treatment-related | 3091 (95.2) | 48 (94.1) | 179 (92.3) | 102 (91.1) | 132 (90.4) | 69 (89.6) |
| SAEs, n (%) | 702 (21.6) | 8 (15.7) | 36 (18.6) | 51 (45.5) | 30 (20.5) | 34 (44.2) |
| Treatment-related | 203 (6.3) | 2 (3.9) | 11 (5.7) | 15 (13.4) | 10 (6.8) | 10 (13.0) |
| Fatal SAEs | 62 (1.9) | 2 (3.9) | 4 (2.1) | 7 (6.3) | 4 (2.7) | 6 (7.8) |
| Treatment-related | 14 (0.4) | 1 (2.0) | 0 | 1 (0.9) | 0 | 1 (1.3) |
| AEs leading to discontinuation, n (%) | 528 (16.3) | 7 (13.7) | 25 (12.9) | 15 (13.4) | 18 (12.3) | 10 (13.0) |
| Treatment-related | 418 (12.9) | 4 (7.8) | 19 (9.8) | 10 (8.9) | 13 (8.9) | 7 (9.1) |
| AEs leading to dose adjustment or interruption, n (%) | 2434 (75.0) | 37 (72.5) | 141 (72.7) | 87 (77.7) | 107 (73.3) | 57 (74.0) |
| Treatment-related | 2235 (68.9) | 33 (64.7) | 131 (67.5) | 76 (67.9) | 98 (67.1) | 50 (64.9) |
| AEs requiring additional therapy, n (%) | 2624 (80.8) | 41 (80.4) | 146 (75.3) | 102 (91.1) | 106 (72.6) | 72 (93.5) |
| Treatment-related | 1613 (49.7) | 21 (41.2) | 88 (45.4) | 67 (59.8) | 68 (46.6) | 46 (59.7) |
| Most common TRAEs (≥20% in any subgroup), n (%) | ||||||
| Neutropenia | 2417 (74.5) | 34 (66.7) | 145 (74.7) | 71 (63.4) | 106 (72.6) | 48 (62.3) |
| Nausea | 1166 (35.9) | 14 (27.5) | 51 (26.3) | 41 (36.6) | 38 (26.0) | 32 (41.6) |
| Leukopenia | 887 (27.3) | 12 (23.5) | 59 (30.4) | 30 (26.8) | 43 (29.5) | 20 (26.0) |
| Anemia | 605 (18.6) | 8 (15.7) | 32 (16.5) | 32 (28.6) | 21 (14.4) | 21 (27.3) |
| Vomiting | 649 (20.0) | 8 (15.7) | 26 (13.4) | 28 (25.0) | 21 (14.4) | 19 (24.7) |
| Alopecia |
638 (19.7) |
7 (13.7) |
10 (5.2) |
21 (18.8) |
8 (5.5) |
17 (22.1) |
| Grade ≥3 |
All patients (N = 3246) |
CNS metastasis (n = 51) |
Prior chemotherapy (n = 194) |
ECOG PS 2 (n = 112) |
VM + prior chemotherapy (n = 146) |
VM + ECOG PS 2 (n = 77) |
| AEs, n (%) | 2461 (75.8) | 38 (74.5) | 138 (71.1) | 96 (85.7) | 102 (69.9) | 65 (84.4) |
| Treatment-related | 2192 (67.5) | 33 (64.7) | 126 (64.9) | 71 (63.4) | 92 (63.0) | 45 (58.4) |
| SAEs, n (%) | 590 (18.2) | 6 (11.8) | 30 (15.5) | 45 (40.2) | 26 (17.8) | 30 (39.0) |
| Treatment-related | 178 (5.5) | 2 (3.9) | 11 (5.7) | 13 (11.6) | 10 (6.8) | 8 (10.4) |
| Fatal SAEs | 61 (1.9) | 2 (3.9) | 4 (2.1) | 7 (6.3) | 4 (2.7) | 6 (7.8) |
| Treatment-related | 14 (0.4) | 1 (2.0) | 0 | 1 (0.9) | 0 | 1 (1.3) |
| AEs leading to discontinuation, n (%) | 310 (9.6) | 5 (9.8) | 16 (8.2) | 11 (9.8) | 11 (7.5) | 6 (7.8) |
| Treatment-related | 237 (7.3) | 4 (7.8) | 14 (7.2) | 8 (7.1) | 9 (6.2) | 5 (6.5) |
| AEs leading to dose adjustment or interruption, n (%) | 2095 (64.5) | 31 (60.8) | 119 (61.3) | 77 (68.8) | 89 (61.0) | 49 (63.6) |
| Treatment-related | 1964 (60.5) | 29 (56.9) | 114 (58.8) | 66 (58.9) | 84 (57.5) | 42 (54.5) |
| AEs requiring additional therapy, n (%) | 844 (26.0) | 7 (13.7) | 44 (22.7) | 51 (45.5) | 34 (23.3) | 32 (41.6) |
| Treatment-related | 392 (12.1) | 3 (5.9) | 27 (13.9) | 21 (18.8) | 22 (15.1) | 11 (14.3) |
| Most common TRAEs (≥3% in any subgroup), n (%) | ||||||
| Neutropeniaa | 1856 (57.2) | 26 (51.0) | 104 (53.6) | 57 (50.9) | 77 (52.7) | 35 (45.5) |
| Leukopeniab | 345 (10.6) | 5 (9.8) | 25 (12.9) | 12 (10.7) | 17 (11.6) | 8 (10.4) |
| ALT increased | 249 (7.7) | 3 (5.9) | 12 (6.2) | 4 (3.6) | 8 (5.5) | 3 (3.9) |
| AST increased | 184 (5.7) | 2 (3.9) | 7 (3.6) | 0 | 5 (3.4) | 2 (2.6) |
| GGT increased | 0 | 2 (3.9) | 0 | 0 | 0 | 0 |
| Fatigue | 49 (1.5) | 0 | 2 (1.0) | 4 (3.6) | 1 (0.7) | 2 (2.6) |
AE, adverse event; ALT, alanine aminotransferase; AST, aspartate aminotransferase; CNS, central nervous system; ECOG PS, Eastern Cooperative Oncology Group performance status; GGT, gamma-glutamyl transferase; SAE, serious adverse event; TRAE, treatment-related adverse event; VM, visceral metastases.
Numbers (n) represent counts of patients. A patient with multiple severity grades for an AE was only counted under the maximum grade.
a
Includes “neutropenia” and “neutrophil count decreased.”
b
Includes “leukopenia” and “white blood cell count decreased.