Table 1.
Kinase inhibitors studied and not yet US FDA approved in radioactive iodine-refractory thyroid tumors of follicular origin
| Drug | Histology (descending order in frequency) | Study phase (n) | ORR (%) | PFS (months) | Toxicity common all-grade AEs (descending order in frequency) |
|---|---|---|---|---|---|
| Sunitinib92 | PTC, FTC, Hürthle cell carcinoma, and MTC | II (35) | 31 | 12.8 | Neutropenia, leukopenia, fatigue, diarrhea, HFS |
| Axitinib93 | PTC, FTC, medullary, anaplastic | II (60) | 30 | 18.1 | Fatigue, diarrhea, nausea, anorexia, hypertension, stomatitis, weight loss, and headache |
| Pazopanib94 | FTC, PTC, and Hürthle cell carcinoma | II (37) | 49 | 11.7 | Fatigue, hair and skin hypopigmentation, diarrhea, nausea, vomiting, anorexia, hypertension, and AST/ALT elevations |
| Motesanib95 | PTC, Hürthle cell carcinoma, and FTC | II (93) | 14 | 10 | Diarrhea, hypertension, fatigue, weight loss, abdominal pain, nausea, anorexia, headache, dry mouth, and hypothyroidism |
| Cabozantinib96 | FTC, PTC, and Hürthle cell carcinoma | I (15) | 53 | Not reached for median follow-up of 12.2 months | Diarrhea, hypertension, decreased appetite, and fatigue |
| Vandetanib97 | PTC, FTC, and poorly differentiated carcinoma | II (145) | 8 | 11.1 | Diarrhea, hypertension, acne, asthenia, decreased appetite, rash, QTc prolongation |
| Vemurafenib98 | PTC only# | II (51) | 35–26## | 15.6–6.8## | Rash, fatigue, weight loss, and increased bilirubin |
| Dabrafenib99 | Well differentiated (not specified), poorly differentiated carcinoma, FTC, oncocytic, and Hürthle cell features# | II (14) | 29 | 11.3 | Skin papillomas, hyperkeratosis, alopecia, arthralgia, hair texture abnormality, pyrexia, seborrheic keratosis, and skin hypertrophy |
| Selumetinib100 | PTC and poorly differentiated carcinoma | II (20) | 25* | 35% of patients had disease controlled for at least 6 months** | Fatigue, maculopapular rash, acneiform rash, AST and ALT elevations |
Notes:
In 60% of patients, iodine124 uptake increased after selumetinib therapy; partial responses were observed in 20% (5/20) of patients treated with both iodine124 and selumetinib;
35% (7/20) of the patients who received both therapeutic iodine and selumetinib had sustained partial and stable disease for at least 6 months;
all BRAF-mutated tumors;
best results were seen in the TKI-naïve patient group compared to the TKI-exposed group.
Abbreviations: FDA, Food and Drug Administration; ORR, overall response rate; PFS, progression-free survival; AEs, adverse events; PTC, papillary thyroid carcinoma; FTC, follicular thyroid carcinoma; MTC, medullary thyroid carcinoma; HFS, hand–foot syndrome; AST, aspartate aminotransferase; ALT, alanine aminotransferase; TKI, tyrosine kinase inhibitor; QTc,; PET-CT,.