Table 1.
Incidence of common renal adverse effects of ALK inhibitors based on Kassem et al. and Costa et al. [28, 29]
| Author/study | Study type | Patients, n | Edema, grade 1–2/≥3, n (%) | Electrolyte abnormalities and/or HT, grade 1–2/≥3, n (%) | Increased SCr, grade 1–2/≥3, n (%) |
|---|---|---|---|---|---|
| ALK inhibitor, first generation | |||||
| Crizotinib | |||||
| PROFILE 1001 | IB | 149 | 44 (39)/0 | Hypophosphatemia 2 (4)/5 (10) | |
| PROFILE 1007 | III | 343 | 54 (31)/0 | ||
| PROFILE 1014 | III | 172 | 83 (49)/1(1) | ||
| J-Alec 2017 | III | 104 | NR | 9 (9)/0 | |
| Alex trial | III | 151 | 42 (28)/1 (1) | ||
| Camidge 2018 | III | 138 (Crizo arm) | 6 (4)/1 (1) | HT 31 (23)/13 (10) | 3 (2)/0 |
| Shaw 2020 | III | 142 (Crizo arm) | 54 (38)/18 (12) | HT 3 (2)/0 | |
| ALK inhibitor, second generation | |||||
| Alectinib | |||||
| AF-001JP | I/II | 46 | NR | 12 (26)/0 | |
| AF-001JP, third year | I/II | 58 | NR | 19 (32.8)/0 | |
| NP28673, Global | II | 138 | 34 (25)/0 | ||
| NP28761, North America | II | 87 | 20 (23)/0 | Hypophosphatemia 2 (2.3)/2 (2.3) Hypocalcemia 2 (2.3)/1 (1.1) Hyponatremia 2 (2.3)/1 (1.1) Hypokalemia 6 (6.9)/2 (2.3) |
|
| J-Alec 2017 | I/II | 103 | NR | 11 (11)/0 | |
| J-Alec 2017 | III | 103 | 9 (9)/0 | ||
| Alex trial | III | 152 | 26 (17)/0 | ||
| Ceritinib | |||||
| ASCEND-1 2627 | IB | 246 | NR | Hypophosphatemia 8 (3.3)/8 (3.3) Hyponatremia 8 (3.3)/11 (4.5) Hypokalemia 17 (6.9)/11 (4.5) |
42 (17.1)/0 |
| ASCEND-2 | II | 140 | NR | Hypophosphatemia 7 (5.0)/3 (2.1) Hypokalemia 8 (5.7)/4 (4.9) |
|
| ASCEND-4 | III | 189 | NR | 44 (22)/4 (2) | |
| ASCEND-5 | III | 115 | NR | 22 (19)/0 | |
| ASCEND-6 | I/II | 103 | NR | Hypokalemia 11 (10.7)/8 (7.8) | 34 (33)/0 |
| Real life | 208 | NR | 14 (6.7)/8 (3.8) | ||
| Brigatinib | |||||
| Camidge 2018 | III | 137 (Briga arm) | 53 (39)/1(1) | HT 10 (7)/4 (3) | 19 (14)/1 (1) |
| Gettinger 2016 | I/II | 137 | Dose independent (33%) | HT dose dependent: 6–27% and 0–7% | |
| Kim 2017 | II | 222 | NR | HT dose dependent: 11–21% and 6% | |
| ALK inhibitor, third generation | |||||
| Lorlatinib | |||||
| Bauer | I | 295 | 151 (51.2)/7(2.4) | ||
| Shaw 2017 | I | 54 | 21 (39)/0 | ||
| Solomon 2018 | II | 276 | 113 (41)/6 (2) | Hypophosphatemia 2 (1)/2 (1) Hyponatremia 1 (<1)/1 (<1) HT 4(1)/4(1) |
|
| Shaw 2019 | I/II | 346 | 27 (39)/1(1) | Hypophosphatemia 2 (3)/4 (6) Hyponatremia 0/1 (1) |
|
| Shaw 2020 | I | 149 (Lorla arm) | 76 (51)/6 (4) | HT 12 (8)/15 (10) | |
| Ensartinib | |||||
| Horn 2018 | I/II | 97 | 15 (15)/1 (1) | ||
| Yang 2019 | II | 156 | 14 (9)/2 (1) | 30 (19)/0 | |
| Entrectinib | |||||
| Drillon 2019 | I/II | 53 | 22 (16)/0 | Hypophosphatemia 2 (1)/1 (<1) Hyperuricemia 11 (8)/1 (<1) HT 0/1 (<1) |
17 (13)/1(<1) |
| Doebele 2019 | I/II | 355 | 49 (14)/1 (<1) | Hypophosphatemia 6 (2)/4 (1) Hyperuricemia 13 (4)/5 (1) Hyponatremia 3 (1)/2 (1) HT 0/1 (<1) |
52 (15)/2 (1) |
NR, not reported; HT, hypertension; SCr, serum creatinine.