Table 1.
Adverse events that arose in the two apatinib-related trials (NCT02711007 and NCT03359018).
| Apatinib for Advanced Osteosarcoma (NCT02711007) (N = 37) | Apatinib and Camrelizumab for Advanced Osteosarcoma (NCT03359018) (N = 43) | Apatinib for Stage IV Sarcomas(NCT03121846)(N=64) | Apatinib for Advanced Bone and Soft Tissue Sarcomas(NCT03163381)(N=45) | |||||
|---|---|---|---|---|---|---|---|---|
| All, n (%) | Grade 3/4, n (%) | All, n (%) | Grade 3/4, n (%) | All, n (%) | Grade 3/4, n (%) | All, n (%) | Grade 3/4, n (%) | |
| Cardiac disorders | ||||||||
| Palpitations | 3 (8.11) | 1 (2.70) | 5 (11.63) | 0 (0.00) | 2 (3.13) | 0 (0.00) | NRb | NR |
| Endocrine disorders | ||||||||
| Hypoparathyroidism | 8 (21.62) | 0 (0.00) | 9 (20.93) | 1 (2.33) | NR | NR | NR | NR |
| Gastrointestinal disorders | ||||||||
| Abdominal pain | 4 (10.81) | 2 (5.41) | 8 (18.60) | 2 (4.65) | NR | NR | NR | NR |
| Anal mucositis, ulcer and hemorrhage | 3 (8.10) | 1 (2.70) | 1 (2.33) | 1 (2.33) | NR | NR | NR | NR |
| Diarrhea | 7 (18.92) | 3 (8.10) | 21 (48.84) | 2 (4.65) | 7 (10.94) | 0 (0.00) | 16 (35.56) | 2 (12.50) |
| Oral mucositis | 4 (10.81) | 0 (0.00) | 11 (25.58) | 2 (4.65) | 5 (7.81) | 0 (0.00) | NR | NR |
| Nausea and vomiting | 0 (0.00) | 0 (0.00) | 10 (23.25) | 1 (2.33) | ||||
| Toothache | 0 (0.00) | 0 (0.00) | 6 (13.95) | 2 (4.65) | 3 (4.69) | 0 (0.00) | NR | NR |
| General disorders and administration site conditions | ||||||||
| Fatigue | 12 (32.43) | 1 (2.7) | 4 (9.30) | 1 (2.33) | 8 (12.50) | 1 (1.56) | 16 (35.56) | 1 (6.25) |
| Hepatobiliary disorders | ||||||||
| Cholecystitis | 1 (2.7) | 1 (2.7) | 1 (2.33) | 0 (0.00) | NR | NR | NR | NR |
| Injury, poisoning and procedural complications | ||||||||
| Wound complications | 4 (10.81) | 4 (10.81) | 11 (25.58) | 6 (13.95) | NR | NR | NR | NR |
| Investigations | ||||||||
| Alanine/aspartate aminotransferase increases | 1 (2.70) | 0 (0.00) | 18 (41.86) | 2 (4.65) | 4 (6.25) | 0 (0.00) | NR | NR |
| Blood bilirubin increases | 7 (18.92) | 0 (0.00) | 22 (51.16) | 4 (9.30) | 3 (4.69) | 0 (0.00) | NR | NR |
| Electrocardiogram Prolonged QTc interval | 0 (0.00) | 0 (0.00) | 3 (6.98) | 0 (0.00) | NR | NR | NR | NR |
| Platelet count decreases | 1 (2.70) | 0 (0.00) | 30 (69.77) | 2 (4.65) | NR | NR | NR | 1 (6.25) |
| Thyroid-stimulating hormone increases | 8 (21.62) | 3 (8.11) | 35 (81.4) | 1 (2.33) | NR | NR | NR | NR |
| Weight loss | 12 (32.43) | 1 (2.70) | 15 (34.88) | 3 (6.98) | NR | NR | NR | NR |
| White blood cell decreases | 0 (0.00) | 0 (0.00) | 16 (37.21) | 2 (4.65) | NR | NR | NR | NR |
| Metabolism and nutrition disorders | ||||||||
| Anorexia | 13 (35.14) | 2 (5.41) | 20 (46.51) | 3 (6.98) | 14 (21.88) | 0 (0.00) | NR | NR |
| Hyperlipidemia | 10 (27.03) | 1 (2.70) | 32 (74.42) | 3 (6.98) | NR | NR | NR | NR |
| Hypokalemia | 3 (8.11) | 1 (2.7) | 17 (39.53) | 0 (0.00) | NR | NR | NR | NR |
| Musculoskeletal and connective tissue disorders | ||||||||
| Pain in extremity | 5 (13.51) | 0 (0.00) | 20 (46.51) | 2 (4.65) | 7 (10.94) | 1 (1.56) | NR | NR |
| Psychiatric disorders | ||||||||
| Insomnia | 2 (5.41) | 0 (0.00) | 2 (4.65) | 0 (0.00) | NR | NR | NR | NR |
| Renal and urinary disorders | ||||||||
| Proteinuria | 4 (10.81) | 3 (8.11) | 11 (25.58) | 1 (2.33) | 19 (29.69) | 2 (3.13) | 14 (31.11) | 2 (14.29) |
| Respiratory, thoracic and mediastinal disorders | ||||||||
| Hoarseness and oropharyngeal pain | 0 (0.00) | 0 (0.00) | 3 (6.98) | 0 (0.00) | 4 (6.25) |
0 (0.00) | NR | NR |
| Pneumothorax | 12 (32.43) | 6 (16.22) | 9 (20.93) | 3 (6.98) | 2 (3.13) | 0 (0.00) | NR | NR |
| Skin and subcutaneous tissue disorders | ||||||||
| Hair color changes | 1 (2.70) | 0 (0.00) | 5 (11.63) | 0 (0.00) | 5 (7.81) | 0 (0.00) | NR | NR |
| Hand–foot skin reaction a | 14 (37.84) | 5 (13.51) | 21 (48.84) | 2 (4.65) | 22 (34.38) |
3 (4.69) | 15 (33.33) | 1 (6.67) |
| Vascular disorders | ||||||||
| Hypertension | 7 (18.92) | 0 (0.00) | 10 (23.26) | 2 (4.65) | 24 (37.50) | 5 (7.81) | 17 (37.8) | 2 (12.50) |
a
Hand–foot skin reactions including palmar-plantar erythrodysesthesia syndrome and rash maculo-papular.
b
NR, not reported.