Table 4.
Overview of top 5 adverse effects found in clinical trials of lenvatinib, cabozantinib, and sorafenib in RR-DTC.
| Title | Daily Dose | Most Frequent AEs (Not Including Serious) | Most Frequent Serious AEs |
|---|---|---|---|
| Evaluating the Safety and Efficacy of Oral Lenvatinib in Medullary and Iodine-131 Refractory, Unresectable Differentiated Thyroid Cancers, Stratified by Histology NCT00784303 [83] |
24 mg lenvatinib | Hypertension 77.59% Diarrhea 68.97% Fatigue 60.34% Decreased appetite 55.17% Nausea 51.72% |
Hypotension 6.9% Dehydration 6.9% Hypertension 3.45% Renal failure 3.45 Pneumonia 3.45% |
| A Trial of Lenvatinib (E7080) in Subjects with Iodine-131 Refractory Differentiated Thyroid Cancer to Evaluate Whether an Oral Starting Dose of 18 Milligram (mg) Daily Will Provide Comparable Efficacy to a 24 mg Starting Dose, But Have a Better Safety Profile NCT02702388 |
24 mg or 18 mg lenvatinib (starting dose) | 24 mg: Hypertension 57.33% Diarrhea 56% Proteinuria 42.67% Nausea 40.00% Weight loss 36.00% 18 mg: Hypertension 51.95% Diarrhea 51.95% Weight loss 42.86% Stomatitis 38.57% Nausea 35.06% |
24 mg: Total 33.33% Malignant neoplasm progression 4% Pneumothorax 2.67% Hypertension 1.33% 18 mg: Total 40.26% Osteoarthritis 2.60% Pathological fracture 2.60% Malignant neoplasm progression 2.60% Malignant pleural effusion 2.60% |
| A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Trial of Lenvatinib (E7080) in 131I-Refractory Differentiated Thyroid Cancer (DTC) (SELECT) NCT01321554 [58] |
24 mg lenvatinib Placebo matching the lenvatinib treatment. |
Hypertension 69.35% Diarrhea 69.73% Loss of appetite 56.70% Weight loss 54.41% Nausea 48.66% |
Pneumonia 4.6% Hypertension 3.83 Dehydration 3.45% General physical health deterioration 2.68% Pulmonary embolism 2.3% |
| A Study of E7080 in Subjects with Advanced Thyroid Cancer NCT01728623 |
24 mg lenvatinib | Hypertension 90.20% Palmar-plantar erythrodysaesthesia syndrome 76.47% Loss of appetite 76.47% Fatigue 72.55% Proteinuria 60.78% |
Decreased appetite 13.73% Malignant neoplasm progression 7.84% Pneumonia 5.88% Nausea 3.92% Laryngeal stenosis 3.92% |
| Cabozantinib-S-Malate in Treating Patients with Refractory Thyroid Cancer NCT01811212 [31] |
60 mg cabozantinib S-malate | Liver transaminase elevation 80% Palmar-plantar erythrodysesthesia 76% Fatigue 76% Diarrhea 72% Nausea 64% … Hypertension 48% |
Left ventricular systolic dysfunction 4% Osteonecrosis of the jaw 4% Asymptomatic increased lipase 4% Meningitis 4% Pneumonia 4% |
| A Study of Cabozantinib Compared with Placebo in Subjects with Radioiodine-refractory Differentiated Thyroid Cancer Who Have Progressed After Prior VEGFR-targeted Therapy (COSMIC-311 Trial) NCT03690388 [54] |
60 mg or 20 mg cabozantinib or placebo equivalent once daily | Diarrhea 44% Palmar-plantar erythrodysesthesia 35% Alanine aminotransferase increased 23% Aspartate aminotransferase increased 23% Nausea 21% … Hypertension 19% |
Palmar-plantar erythrodysesthesia 10% Hypertension 9% Fatigue 8% Diarrhoea 7% Hypocalcaemia 7% |
| Safety and Efficacy of Sorafenib in Patients with Advanced Thyroid Cancer: a Phase II Clinical Study NCT02084732 [84] |
800 mg/day sorafenib | Hypertension 42.1% Hand/food Erythema 36.8% Diarrhea 31.5% Muscle pain 21% Rash 21% |
Hypertension 56,8% Hand/food Erythema 31.5% Diarrhea 26.2% Rash 15.7% Acute myocardial infarction 5.2% |
| Sorafenib as Adjuvant to Radioiodine Therapy in Non-Medullary Thyroid Carcinoma NCT00887107 [85] |
800 mg/day sorafenib | Weight loss 47.6% Diarrhea 50% Alopecia 47% Rash 47% Hand foot syndrome 43.6% … Hypertension 25.4% |
Hand foot syndrome 21.8% Hypertension 15% Weight loss 8.4% Myocardial infarction 3% Congestive heart disease 3% |
| A Double-Blind Randomized Phase III Study Evaluating the Efficacy and Safety of Sorafenib Compared to Placebo in Locally Advanced/Metastatic RAI-Refractory Differentiated Thyroid Cancer (DECISISON) NCT00984282 [56] |
800 mg/day sorafenib | Alopecia 67.1% Diarrhea 62.8% Hand–foot skin reaction 56% Rash 45.4% Fatigue 44% Hypertension 30.9% |
Hand–foot skin reaction 20.3% Hypertension 9.7% Hypocalcemia 9.2 Diarrhea 5.8% Fatigue 5.8% |
If hypertension was not among the top 5 AEs, it is still listed, separated by “…” from the rest.