Table 2.
Treatment-emergent adverse events reported in at least 10% of the patients in the two treatment arms
| Gefitinib + anlotinib (N = 155) |
Gefitinib + placebo (N = 155) |
|||
|---|---|---|---|---|
| Any grade | Grade 3 or higher | Any grade | Grade 3 or higher | |
| Any TEAEs | 154 (99.4) | - | 151 (97.42) | - |
| Grade ≥ 3 TEAEs | - | 77 (50.0) | - | 48 (31.0) |
| Serious TEAEs | 17 (11.0) | - | 9 (5.8) | - |
| TEAEs leading to dose interruption, any drug | 50 (32.3) | - | 34(21.9) | - |
| TEAEs leading to dose reduction, any drug | 48 (31.0) | - | 21 (13.6) | - |
| Discontinued treatment due to TEAEs | 16 (10.3) | - | 7 (4.5) | - |
| $ TEAEs leading to death | 2 (1.3) | - | 1 (0.7) | - |
| TEAEs (≥ 10%) | ||||
| Diarrhea | 103 (66.5) | 0 (0.0) | 63 (40.7) | 2 (1.3) |
| Rash | 102 (65.8) | 5 (3.23) | 82 (52.90) | 0 (0.0) |
| Hypertension | 101 (65.2) | 46 (29.68) | 42 (27.10) | 8 (5.2) |
| ALT increased | 73 (47.1) | 10 (6.45) | 75 (48.39) | 19 (12.3) |
| AST increased | 70 (45.2) | 5 (3.23) | 75 (48.39) | 11 (7.1) |
| Proteinuria | 68 (43.9) | 3 (1.94) | 38 (24.52) | 0 (0.0) |
| Hypertriglyceridemia | 65 (41.9) | 4 (2.58) | 54 (34.84) | 2 (1.3) |
| Occult blood positive | 58 (37.4) | 0 (0.00) | 58 (37.42) | 0 (0.0) |
| Palmoplantar redness syndrome | 51 (32.9) | 3 (1.94) | 24 (15.48) | 0 (0.0) |
| Hypercholesterolemia | 43 (27.7) | 0 (0.00) | 28 (18.06) | 0 (0.0) |
| Dysphonia | 42 (27.1) | 0 (0.00) | 1 (0.65) | 0 (0.0) |
| Urine occult blood positive | 41 (26.5) | 0 (0.00) | 35 (22.58) | 2 (1.29) |
| Cough | 35 (22.6) | 0 (0.00) | 34 (21.94) | 0 (0.00) |
| Anorexia | 35 (22.6) | 0 (0.00) | 16 (10.32) | 1 (0.65) |
| Dizzy | 35 (22.6) | 0 (0.00) | 25 (16.13) | 1 (0.65) |
| Urine white blood cell positive | 31 (20.0) | 1 (0.65) | 23 (14.84) | 1 (0.65) |
| Mouth ulcer | 29 (18.7) | 0 (0.00) | 17 (10.97) | 0 (0.00) |
| Gingival bleeding | 29 (18.7) | 0 (0.00) | 14 (9.03) | 0 (0.00) |
| Weakness | 28 (18.1) | 0 (0.00) | 14 (9.03) | 0 (0.00) |
| Nosebleed | 26 (16.8) | 1 (0.65) | 17 (10.97) | 0 (0.00) |
| Headache | 26 (16.8) | 0 (0.00) | 14 (9.03) | 0 (0.00) |
| Hypokalemia | 25 (16.1) | 2 (1.29) | 12 (7.74) | 1 (0.65) |
| Oral mucositis | 25 (16.1) | 3 (1.94) | 8 (5.16) | 0 (0.00) |
| Hematuria | 25 (16.1) | 1 (0.65) | 15 (9.68) | 0 (0.00) |
| Vomiting | 24 (15.5) | 1 (0.65) | 15 (9.68) | 0 (0.00) |
| Hyperuricemia | 23 (14.8) | 0 (0.00) | 27 (17.42) | 0 (0.00) |
| Pruritus | 23 (14.8) | 0 (0.00) | 27 (17.42) | 0 (0.00) |
| Urine red blood cell positive | 22 (14.2) | 0 (0.00) | 15 (9.68) | 0 (0.00) |
| Back pain | 21 (13.6) | 0 (0.00) | 27 (17.42) | 0 (0.00) |
| Paronychia | 21 (13.6) | 1 (0.65) | 20 (12.90) | 0 (0.00) |
| Joint pain | 20 (12.9) | 0 (0.00) | 14 (9.03) | 0 (0.00) |
| Chest pain | 18 (11.6) | 0 (0.00) | 23 (14.84) | 0 (0.00) |
| Nasopharyngitis | 17 (11.0) | 0 (0.00) | 17 (10.97) | 0 (0.00) |
| Constipation | 17 (11.0) | 0 (0.00) | 15 (9.68) | 0 (0.00) |
| Hemoptysis | 17 (11.0) | 2 (1.29) | 14 (9.03) | 0 (0.00) |
| Fever | 16 (10.3) | 0 (0.00) | 6 (3.87) | 0 (0.00) |
| Abdominal pain | 16 (10.3) | 0 (0.00) | 8 (5.16) | 0 (0.00) |
| Blood bilirubin increased | 16 (10.3) | 0 (0.00) | 22 (14.19) | 1 (0.65) |
| Gingival pain | 16 (10.3) | 0 (0.00) | 5 (3.23) | 0 (0.00) |
| Limb pain | 16 (10.3) | 0 (0.00) | 13 (8.39) | 1 (0.65) |
ALT, alanine aminotransferase; AST, aspartate aminotransferase; TEAEs, treatment emergent adverse events
Treatment-emergent adverse events were evaluated throughout the treatment period and to 30 days post the final dose using NCI CTC AE version 4.0 and coded using MedDRA 24.0
Gefitinib + anlotinib: 1 patient reported multiple cerebral infarctions leading to death, and 1 patient reported dyspnea leading to death
Gefitinib + placebo: 1 patient reported Pulmonary hypertension leading to death