Table 3.
Commercially Available Drugs Studied in Treatment of Thyroid Cancer
| Drug | Mechanism of Action: Target(s) | FDA-Approved Indication | Number of Patients With Thyroid Cancer Enrolleda | Results in Patients With Thyroid Cancer | Common Adverse Events | References |
|---|---|---|---|---|---|---|
| Axitinib | TKI: VEGFR1–3 | RCC | DTC: 45 | 30% PR (responses not broken down by histology) | HTN, HFSR, diarrhea, fatigue | Cohen et al. (53) |
| MTC: 11 | ||||||
| ATC: 2 | ||||||
| DTC: 34 | DTC: 2/34 CR, 8/34 PR | Capdevila et al. (54) | ||||
| MTC: 13 | MTC: 3/13 PR | |||||
| Cabozantinib | TKI: VEGFR2, MET, FLT3, RET, c-kit | MTC, RCC, HCC | MTC: 219 | MTC: 28% PR | HTN, HFSR, diarrhea, fatigue | Elisei et al. (55) |
| DTC (second or third line): 25 | DTC: 40% PR | Cabanillas et al. (56) | ||||
| Dabrafenib (single agent) | STKI: BRAF V600E | BRAF-mutated melanoma | DTC: 13 | DTC: 4/13 PR | Fever, diarrhea, skin rash and skin growths (including SCC), HFSR, fatigue | Falchook et al. (57) |
| Dabrafenib in combination with trametinib | STKI: dabrafenib, BRAF V600E | BRAF-mutated ATC, melanoma, non–small cell lung cancer | ATC: 16 | ATC: 63% PR (by central review) | Acneiform rash (trametinib); see “dabrafenib” for other AEs, but some AEs decreased with addition of trametinib | Subbiah et al. (58) |
| STKI: trametinib, MEK1/2 | ||||||
| Everolimus | STKI: mTOR | RCC, SEGA, TS | DTC: 85 | DTC: 2/85 PRb | Mucositis, myelosuppression, infection | Lim et al. (59) |
| MTC: 19 | MTC: 2/19 PR | Schneider et al. (60, 61) | ||||
| ATC: 13 | ATC: 1/13 PR | Hanna et al. (62) | ||||
| Lenvatinib | TKI: VEGFR1–3, FGFR1–4, PDGFR, RET, c-kit | DTC; approved for RCC in combination with everolimus | DTC: 261 | DTC: 65% CR + PR | HTN, HFSR, diarrhea, fatigue | Schlumberger et al. (63, 64) |
| MTC: 59 | MTC: 36% PR | Tahara et al. (65) | ||||
| ATC: 17 | ATC: 24% PR | |||||
| Larotrectinib | TrkI: NTRK fusions | Adult and pediatric patients with solid tumors and NTRK fusions (tumor agnostic) | NTRK-fusion thyroid carcinoma (histologies not reported): 5 | 5/5 PR | Fatigue, dizziness, nausea, LFT elevation | Drilon et al. (66) |
| Pazopanib | TKI: VEGFR1–3 PDGFR, FGFR1/2, c-kit | RCC | DTC: 37 | DTC: 49% PR | HTN, HFSR, diarrhea, fatigue, hypopigmentation | Bible et al. (67–69) |
| MTC: 35 | MTC: 14% PR | |||||
| ATC: 15 | ATC: 0% responses | |||||
| Sorafenib | TKI: VEGFR1–3, PDGFR, RET, c-kit, BRAF | DTC, HCC, RCC | DTC: 209 | DTC: 12% PR | HTN, HFSR, diarrhea, fatigue | Brose et al. (70) |
| MTC: 31b | MTC: 8/31 (25%) PR | Lam et al. (71) Capdevila et al. (72) | ||||
| ATC: 3 | ATC: 1/3 PR | |||||
| Sunitinib | TKI: VEGFR1–3, PDGFR, RET, c-kit, CSF-1R, Flt-3 | GIST, RCC, pNET | DTC: 23 | DTC: 26% PR | HTN, HFSR, diarrhea, fatigue, hypopigmentation | Bikas et al. (73) |
| MTC: 58 | MTC: 24% PR | Carr et al. (74) | ||||
| Ravaud et al. (75) | ||||||
| Vandetanib | TKI: VEGFR2/3, EGFR, RET | MTC | MTC: 231 | MTC: 45% PR | HTN, HFSR, diarrhea, photosensitivity, fatigue | Wells et al. (76) |
| DTC: 72 | DTC: 6/72 PR | Leboulleux et al. (77) | ||||
| Vemurafenib | STKI: BRAF V600E | BRAF-mutated melanoma | PTC: 51 | Treatment naive: 39% PR | Skin rash and skin growths (including SCC), photosensitivity, alopecia, fatigue | Brose et al. (78) |
| Previous VEGFR: 27% PR |
Note that only peer-reviewed published trials are included.
Abbreviations: AE, adverse event; CSF-1R, colony-stimulating factor 1 receptor; FGFR1–4, FGF receptors 1–4; GIST, gastrointestinal stromal tumor; HCC, hepatocellular carcinoma; HFSR, hand-foot skin reaction; HTN, hypertension; pNET, pancreatic neuroendocrine tumor; RCC, renal cell carcinoma; SCC, squamous cell carcinoma; SEGA, subependymal giant cell astrocytoma; STKI, serine-threonine kinase inhibitor; TrkI, tropomyosin receptor kinase inhibitor; TS, tuberous sclerosis.
a
Data from the highest-phase trials were used. When more than one trial of the same phase was available, their data were pooled.
b
Pooled data.