Table 2.
Novel Targeted Therapeutics in Iodine Resistant Thyroid Cancer.
| Therapeutic | Target | Indication | Best evidence |
|---|---|---|---|
| FDA Approved for Thyroid Cancer Treatment | |||
| sorafenib | VEGFR 1-3, PDGFR, RET, c-KIT, BRAF | Locally recurrent or metastatic, progressive, differentiated thyroid carcinoma refractory to RAI | Phase III (35) |
| lenvatinib | VEGFR 1-3, FGFR 1-4, PDGFR, RET, c-KIT | Locally recurrent or metastatic, progressive, differentiated thyroid carcinoma refractory to RAI | Phase III (36) |
| dabrafenib and trametinib | BRAF/MEK | BRAF V600E mutated anaplastic thyroid cancer with no satisfactory locoregional treatment options | Phase II (37) |
| selpercatinib | RET | RET-mutant medullary thyroid cancer, RET fusion-positive thyroid cancer refractory to RAI | Phase II (38) |
| pralsetinib | RET | RET-mutant medullary thyroid cancer, RET fusion-positive thyroid cancer refractory to RAI | Phase II NCT03037385 |
| larotrectinib | TRKs | Metastatic or unresectable solid tumors with NTRK gene fusions and no alternative treatments | Phase II (39, 40) |
| entrectinib | TRKs, ALK, ROS | Metastatic or unresectable solid tumors with NTRK gene fusions and no alternative treatments | Phase II (41) |
| cabozantinib | VEGFR, MET, RET, AXL | Medullary thyroid cancer | Phase II/III |
| vandetanib | VEGFR, EGFR, c-KIT, RET | Medullary thyroid cancer | Phase II/III |
| Other FDA Approved Therapeutics with Off-Label Evidence or Ongoing Trial in RAI-R TC | |||
| sunitinib | VEGFR 1-2, PDGFR, CKIT, RET, CSF1R | Advanced DTC resistant to RAI | Phase II (42) |
| pazopanib | VEGFR, FGFR, PDGFR, RET, c- KIT | Advanced DTC resistant to RAI, no effect on ATC | Phase II (43, 44) |
| axitinib | VEGFR, PDGFR, c-KIT | Advanced DTC resistant to RAI, limited ATC data | Phase II (45) |
| anlotinib | VEGFR, PDGFR, FGFR | Advanced DTC resistant to RAI, ATC | Preclinical Phase II pending (NCT02586337) |
| cabozantinib | VEGFR, MET, RET, AXL | Advanced DTC resistant to RAI who failed prior VEGF therapy | Phase II (46) Phase III pending (NCT03690388) |
| vandetanib | VEGFR, EGFR, c-KIT, RET | Advanced DTC resistant to RAI | Phase III (NCT01876784) |
| donafenib | VEGFR, PDGFR | Advanced DTC resistant to RAI | Phase II (47) Phase III pending (NCT03602495) |
| dabrafenib | BRAF | Advanced BRAF V600E mutated DTC resistant to RAI | Phase II (48) |
| vemurafenib | BRAF | Advanced BRAF V600E mutated DTC resistant to RAI, BRAF V600E mutated ATC | Phase II (49) |
| encorafenib | BRAF | Advanced BRAF V600E mutated DTC resistant to RAI | Preclinical Phase II pending (NCT04061980) |
| selumetinib | MEK | Increases iodine uptake in advanced mutated DTC resistant to RAI, no antitumor effects in clinical trial | Phase II/II (50–52), Phase II |
| everolimus | mTOR | Advanced DTC resistant to RAI, ATC | Phase II (53) |
| lapatinib | HER2 | Advanced BRAF V600E mutated IRTC in combination with dabrafenib | Preclinical Phase I pending (NCT01947023) |
| PRRT | Somatostatin analog | Advanced DTC resistant to RAI | Phase II (54) |
| pembrolizumab | PDL-1 | Advanced PDL-1 expressing DTC resistant to RAI, in ATC combined with chemotherapy with questionable results | Phase I (55, 56) Phase II |
| nivolumab | PD-1 | Advanced DTC resistant to RAI/ATC, combined with ipilimumab | Phase II pending (NCT 03246958) |
| ipilimumab | CTLA4 | Advanced DTC resistant to RAI/ATC, combined with nivolumab | Phase II pending (NCT 03246958) |