Table 2.
Overview of adverse effects (AEs).
| Reference | Drug + Starting Dose | Prevalence of AEs | AEs in ≥50% of Patients |
|---|---|---|---|
| Balmelli et al., 2018 [35] | Lenvatinib, 24 mg | 92% | Fatigue (50%) |
| Gianoukakis et al., 2018 [36] | Lenvatinib, 24 mg | 80.8%a | N/A |
| Hu et al., 2019 [37] | Vandetanib, 150 mg, 300 mg | 150 mg: 97.5% 300 mg: 97.6% |
None ≥50% |
| Iwasaki et al., 2018 [33] | Lenvatinib, 24 mg, 20 mg | 100% | Hypertension (91%) Fatigue and anorexia (65%) Proteinuria (61%) |
| Iwasaki et al., 2019 [38] | Sorafenib, lenvatinib | N/A | N/A |
| Jerkovich et al., 2019 [39] | Sorafenib | 90% | Palmar-plantar erythrodysesthesia syndrome (67%) Diarrhea (52%) Hypertension (52%) |
| Kim et al., 2018 [40] | Sorafenib Mean daily dose 666 ± 114 mg |
95% | Palmar-plantar erythrodysesthesia syndrome (76%) |
| Kim et al., 2019 [41] | Sorafenib Mean daily dose: 602 mg |
64%b | N/A |
| Kim et al., 2019 [42] | Sorafenib: ≤400 mg–800 mg Lenvatinib: 20 mg |
N/A | Lenvatinib: Palmar-plantar erythrodysesthesia syndrome (56.5%) Diarrhea (82.6%) Hypertension (78.3%) Decreased weight (52.2%) Sorafenib: Palmar-plantar erythrodysesthesia syndrome (87.5%) Diarrhea (62.5%) Anorexia (60.4%) Alopecia (56.3%) Mucositis (52.1%) Generalized weakness (50%) |
| Kocsis et al., 2018 [43] | Sorafenib 400 mg × 2 |
100% | Fatigue (60%) Palmar-plantar erythrodysesthesia syndrome (50%) Rash/dermatitis (50%) |
| Koyama et al., 2018 [44] | Lenvatinib 24 mg | 100% | Proteinuria (100%) Hypothyroidism (80%) Hypertension (80%) Fatigue (80%) Anorexia (80%) Decreased weight (80%) |
| Locati et al., 2019 [32] | Lenvatinib 24 mg for 71% of patients | 87.2% | N/A |
| Molina-Vega et al., 2018 [34] | Sorafenib: 800 mg or 400 mg Lenvatinib: mean dose 21.6 mg |
100% | Sorafenib: Fatigue (68.7%) Palmar-plantar erythrodysesthesia syndrome (68.7%) Diarrhea (62.5%) Lenvatinib: Fatigue (100%) Hypertension (80%) Palmar-plantar erythrodysesthesia syndrome (60%) Diarrhea (60%) |
| Nervo et al., 2018 [45] | Lenvatinib 24 mg | 100% | Decreased weight (91.7%) Palmar-plantar erythrodysesthesia syndrome (91.7%) Hypertension (75%) Nausea (75%) Diarrhea (66.7%) Fatigue (58.3%) Oral mucositis (58.3%) Decreased appetite (58.3%) Myalgia (58.3%) Arthralgia (50%) |
| Sugino et al., 2018 [46] | Lenvatinib 24 mg | 100% | Hypertension (75.9%) Palmar-plantar erythrodysesthesia syndrome (58.6%) |
| Suzuki et al., 2019 [47] | Lenvatinib 24 mg | 96.2%d | Proteinuria (61.5%)d Malaise (57.7%)d |
| Tahara et al., 2019 [48] | Lenvatinib 24 mg | Group 1e: 100% Group 2f: 99.2% |
Group 1: Diarrhea (73.9%) Hypertension (69.4%) Decreased weight (56.7%) Group 2: Hypertension (69.3%) Decreased appetite (62.2%) Diarrhea (58.3%) |
| Takahashi et al., 2019 [49] | Lenvatinib 24 mg | 100% | RAI-refractory DTC: Hypertension (96%) Palmar-plantar erythrodysesthesia syndrome (92%) Fatigue (80%) Decreased appetite (68%) Stomatitis (68%) Proteinuria (60%) Diarrhea (60%) Arthralgia (56%) MTC: Decreased appetite (100%) Hypertension (89%) Palmar-plantar erythrodysesthesia syndrome (89%) Diarrhea (89%) Fatigue (78%) Proteinuria (67%) Insomnia (56%) ATC: Hypertension (82%) Decreased appetite (82%) Fatigue (59%) Proteinuria (59%) Nausea (59%) Insomnia (56%) |
| Wirth et al., 2018 [50] | Lenvatinib 24 mg | 100%g | Hypertension (100%)g |
| Yamazaki et al., 2019 [51] | Lenvatinib 24, 20, 14, 10 mg | Full dose: Unknown Low dose: 100% |
Full dose: Hypertension (93%) Proteinuria (77%) Palmar-plantar erythrodysesthesia syndrome (77%) Low dose: Hypertension (100%) Proteinuria (83%) Palmar-plantar erythrodysesthesia syndrome (67%) |
a ≥Grade 3 AE; b marked as severe; c also includes lenvatinib as second-line treatment; d dose reduction because of AEs; e Group 1: duration of dose interruption <10%; f Group 2: duration of dose interruption ≥10%; g treatment-emergent hypertension was an inclusion criterium. N/A: not available