Table 2.
Descriptions of main ADRs associated with TKIs for NSCLC treatment and reported into the RAM system.
| Adverse Drug Reaction, n (%) | EGFRi | ALKi | VEGFi | Total (n = 3,048) | |||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| AFT (n = 435) | ERL (n = 1,448) | GEF (n = 366) | OSI (n = 276) | ALEC (n = 140) | BRG (n = 10) | CER (n = 52) | CRIZ (n = 274) | LORL (n =10) | NTB (n = 37) | ||
| Skin and subcutaneous tissue disorders | 277 (63.7) | 1,120 (77.3) | 214 (58.5) | 99 (35.9) | 25 (17.9) | 5 (50.0) | 2 (3.0) | 20 (7.3) | 4 (10.8) | 1,766 | |
| Rash | 132 (30.3) | 605 (41.8) | 103 (28.1) | 35 (12.7) | 17 (12.1) | 2 (20.0) | 1 (1.9) | 6 (2.2) | 901 | ||
| Dermatitis | 22 (5.1) | 133 (9.2) | 20 (5.5) | 2 (0.7) | 1 (10.0) | 178 | |||||
| Pruritus | 19 (4.4) | 99 (6.8) | 24 (6.6) | 16 (5.8) | 2 (1.4) | 3 (1.1) | 163 | ||||
| Skin toxicity | 38 (8.7) | 73 (5.0) | 12 (3.3) | 9 (3.3) | 1 (10.0) | 2 (0.7) | 135 | ||||
| Nail and nail bed conditions | 50 (11.5) | 38 (2.6) | 17 (4.6) | 18 (6.5) | 1 (0.4) | 2 (5.4) | 126 | ||||
| Gastrointestinal disorders | 268 (61.6) | 378 (26.1) | 101 (27.6) | 77 (27.9) | 32 (22.9) | 2 (20.0) | 38 (73.1) | 97 (35.4) | 31 (83.8) | 1,024 | |
| Diarrhea | 175 (40.2) | 214 (14.8) | 46 (12.6) | 42 (15.2) | 3 (2.1) | 5 (9.6) | 12 (4.4) | 16 (43.2) | 513 | ||
| Nausea | 16 (3.7) | 36 (2.5) | 11 (3.0) | 7 (2.5) | 3 (2.1) | 2 (20.0) | 7 (13.5) | 24 (8.8) | 106 | ||
| Vomiting | 15 (3.4) | 25 (1.7) | 8 (2.2) | 3 (1.1) | 4 (2.9) | 11 (21.2) | 20 (7.3) | 1 (2.7) | 87 | ||
| Abdominal pain | 5 (1.1) | 20 (1.4) | 8 (2.2) | 4 (1.4) | 2 (1.4) | 7 (13.5) | 12 (4.4) | 1 (2.7) | 59 | ||
| Stomatitis | 22 (5.1) | 26 (1.8) | 4 (1.1) | 4 (1.4) | 1 (0.7) | 1 (0.4) | 58 | ||||
| General disorders and administration site conditions | 89 (20.5) | 202 (14.0) | 42 (11.5) | 47 (17.0) | 48 (34.3) | 3 (30.0) | 14 (26.9) | 67 (24.5) | 4 (40.0) | 20 (54.1) | 536 |
| Asthenia | 15 (3.4) | 85 (5.9) | 15 (4.1) | 14 (5.1) | 18 (12.9) | 6 (11.5) | 12 (4.4) | 5 (13.5) | 170 | ||
| Mucosal inflammation | 33 (7.6) | 30 (2.1) | 3 (0.8) | 4 (1.4) | 1 (0.4) | 71 | |||||
| Oedema peripheral | 2 (0.5) | 3 (0.2) | 1 (0.3) | 9 (6.4) | 2 (20.0) | 2 (3.8) | 28 (10.2) | 2 (20.0) | 49 | ||
| Pyrexia | 6 (1.4) | 13 (0.9) | 3 (0.8) | 3 (1.1) | 2 (1.4) | 3 (5.8) | 7 (2.6) | 37 | |||
| Xerosis | 3 (0.7) | 20 (1.4) | 1 (0.3) | 24 | |||||||
| Infections and infestations | 79 (18.2) | 296 (20.4) | 49 (13.4) | 34 (12.3) | 10 (7.1) | 1 (1.9) | 13 (4.7) | 1 (2.7) | 483 | ||
| Folliculitis | 23 (5.3) | 136 (9.4) | 16 (4.4) | 3 (1.1) | 178 | ||||||
| Conjunctivitis | 18 (4.1) | 72 (5.0) | 6 (1.6) | 6 (2.2) | 102 | ||||||
| Rash pustular | 5 (1.1) | 18 (1.2) | 3 (0.8) | 1 (0.4) | 27 | ||||||
| Hepatobiliary disorders | 15 (3.4) | 63 (4.4) | 111 (30.3) | 32 (11.6) | 57 (40.7) | 31 (59.6) | 98 (35.8) | 12 (32.4) | 419 | ||
| Hypertransaminasaemia | 5 (1.1) | 14 (1.0) | 78 (21.3) | 14 (5.1) | 20 (14.3) | 10 (19.2) | 58 (21.2) | 10 (27.0) | 209 | ||
| Liver injury | 3 (0.7) | 1 (0.1) | 15 (4.1) | 5 (1.8) | 6 (4.3) | 5 (9.6) | 15 (5.5) | 50 | |||
| Hyperbilirubinaemia | 18 (1.2) | 4 (1.1) | 1 (0.4) | 18 (12.9) | 2 (3.8) | 1 (0.4) | 44 | ||||
| Respiratory, thoracic and mediastinal disorders | 33 (7.6) | 92 (6.4) | 44 (12.0) | 53 (19.2) | 28 (20.0) | 1 (10.0) | 6 (11.5) | 40 (14.6) | 3 (30.0) | 9 (24.3) | 309 |
| Dyspnoea | 6 (1.4) | 35 (2.4) | 8 (2.2) | 10 (3.6) | 8 (5.7) | 1 (1.9) | 6 (2.2) | 74 | |||
| Interstitial lung disease | 7 (1.6) | 7 (0.5) | 8 (2.2) | 13 (4.7) | 3 (2.1) | 1 (10.0) | 14 (5.1) | 1 (10.0) | 54 | ||
| Respiratory failure | 4 (0.9) | 8 (0.6) | 7 (1.9) | 8 (2.9) | 3 (2.1) | 5 (1.8) | 2 (5.4) | 37 | |||
| Blood and lymphatic system disorders | 4 (0.9) | 32 (2.2) | 21 (5.7) | 46 (16.7) | 18 (12.9) | 20 (7.3) | 19 (51.4) | 160 | |||
| Neutropenia | 5 (0.3) | 5 (1.4) | 8 (2.9) | 5 (3.6) | 23 (8.4) | 7 (18.9) | 53 | ||||
| Thrombocytopenia | 3 (0.2) | 6 (1.6) | 28 (10.1) | 1 (0.7) | 1 (1.9) | 39 | |||||
| Anaemia | 1 (0.2) | 16 (1.1) | 6 (1.6) | 5 (1.8) | 6 (2.9) | 1 (0.4) | 1 (2.7) | 36 | |||
| Metabolism and nutrition disorders | 27 (6.2) | 65 (4.5) | 14 (3.8) | 10 (3.6) | 12 (8.6) | 11 (21.2) | 17 (6.2) | 2 (20.0) | 158 | ||
| Decreased appetite | 12 (2.8) | 46 (3.2) | 6 (1.6) | 7 (2.5) | 6 (11.5) | 6 (2.2) | 83 | ||||
| Abnormal loss of weight | 2 (0.5) | 16 (1.1) | 7 (1.9) | 4 (1.4) | 1 (0.7) | 2 (3.8) | 1 (2.7) | 33 | |||
| Hypercreatininaemia | 3 (0.7) | 8 (0.6) | 3 (0.8) | 2 (0.7) | 2 (1.4) | 5 (9.6) | 5 (1.8) | 28 | |||
| Nervous system disorders | 9 (2.1) | 41 (2.8) | 34 (9.3) | 15 (5.4) | 5 (3.6) | 3 (5.8) | 22 (8.0) | 5 (50.0) | 10 (27.0) | 144 | |
| Paresthesia | 1 (0.2) | 5 (0.3) | 2 (0.5) | 3 (1.1) | 2 (5.4) | 13 | |||||
| Dysgeusia | 1 (0.2) | 3 (0.2) | 1 (0.3) | 3 (1.1) | 8 | ||||||
| Neoplasm bening, malignant and unspecified | 17 (3.9) | 8 (0.6) | 20 (5.5) | 47 (17.0) | 1 (0.7) | 1 (10.0) | 1 (1.9) | 15 (5.5) | 13 (35.1) | 123 | |
| Neoplasm progression | 15 (3.4) | 2 (0.1) | 12 (3.3) | 37 (13.4) | 4 (2.9) | 1 (10.0) | 1 (1.9) | 14 (5.1) | 17 (45.9) | 103 | |
| Eye disorders | 19 (4.4) | 59 (4.1) | 7 (1.9) | 5 (1.8) | 1 (0.7) | 22(8.0) | 113 | ||||
| Visual impairment | 1 (0.2) | 4 (0.3) | 1 (03) | 7 (2.6) | 13 | ||||||
| Blepharitis | 3 (0.7) | 6 (0.4) | 1 (0.3) | 1 (0.4) | 11 | ||||||
| Ocular hyperaemia | 4 (0.9) | 3 (0.2) | 2 (0.5) | 1 (0.4) | 1 (0.4) | 11 | |||||
| Cardiac disorders | 1 (0.2) | 14 (1.0) | 4 (1.1) | 27 (9.8) | 7 (5.0) | 6 (11.5) | 27 (9.9) | 3 (8.1) | 89 | ||
| Bradycardia | 1 (0.7) | 4 (7.7) | 18 (6.6) | 23 | |||||||
| Cardiac failure | 9 (3.3) | 4 (1.5) | 2 (5.4) | 15 | |||||||
| Cardiac fibrillation | 1 (0.2) | 1 (0.1) | 5 (1.8) | 2 (1.4) | 9 | ||||||
| Investigations | 2 (0.5) | 9 (0.6) | 17 (4.6) | 17 (6.2) | 13 (9.3) | 1 (10.0) | 14 (26.9) | 10 (3.6) | 3 (30.0) | 86 | |
| Electrocardiogram QT prolonged | 7 (2.5) | 5 (9.6) | 2 (0.7) | 14 | |||||||
| Gamma-glutamyltransferase increased | 1 (0.1) | 3 (0.8) | 1 (0.4) | 1 (1.9) | 4 (1.5) | 10 | |||||
| Musculoskeletal and connective tissue disorders | 11 (2.5) | 16 (1.1) | 9 (2.5) | 7 (2.5) | 14 (10.0) | 2 (3.8) | 3 (1.1) | 1 (10.0) | 63 | ||
| Myalgia | 4 (0.9) | 1 (0.1) | 2 (0.7) | 7 (5.0) | 1 (10.0) | 15 | |||||
| Muscle spasms | 3 (0.7) | 2 (0.1) | 3 (0.8) | 3 (1.1) | 1 (0.7) | 12 | |||||
| Vascular disorders | 3 (0.7) | 19 (1.3) | 8 (2.2) | 16 (5.8) | 1 (0.7) | 1 (10.0) | 8 (2.9) | 2 (5.4) | 58 | ||
| Hypotension | 1 (0.2) | 5 (0.3) | 1 (0.3) | 1 (0.4) | 5 (1.8) | 13 | |||||
| Deep vein thrombosis | 2 (0.1) | 2 (0.7) | 1 (12.5) | 1 (0.4) | 2 (5.4) | 8 | |||||
| Flushing | 2 (0.5) | 4 (0.3) | 2 (0.7) | 8 | |||||||
| Renal and urinary disorders | 10 (2.3) | 10 (0.7) | 8 (2.2) | 4 (1.4) | 5 (3.6) | 10 (3.6) | 1 (10.0) | 1 (2.7) | 49 | ||
| Renal failure | 9 (2.1) | 4 (0.3) | 1 (0.3) | 3 (1.1) | 3 (2.1) | 2 (0.7) | 22 | ||||
| Renal cyst | 7 (2.6) | 7 | |||||||||
| Injury, poisoning and procedural complications | 13 (3.0) | 7 (0.5) | 11 (30.) | 4 (1.4) | 3 (2.1) | 1 (10.0) | 2 (0.7) | 41 | |||
| Off label use | 3 (0.7) | 4 (1.1) | 1 (0.4) | 1 (10.0) | 9 | ||||||
Bold type intended as System Organ Classes. ADR, adverse drug reaction; AFT, afatinib; ALEC, alectinib; ALKi, anaplastic lymphoma kinase inhibitors; BRG, brigatinib; CER, ceritinib; CRIZ, crizotinib; EGFRi, epidermal growth factor receptor inhibitors; ERL, erlotinib; GEF, gefitinib; LORL, lorlatinib; NSCLC, non-small cell lung cancer; NTB, nintedanib; OSI, osimertinib; TKIs, tyrosine kinase inhibitors; VEGFi, vascular endothelial growth factor inhibitor.