Table 1.
FDA-approved targeted therapy for thyroid cancer
| Agent | Target(s) | Thyroid indication(s) | Trial registration (reference) | Design | Histology (case no.) | ORR | Median PFS |
|---|---|---|---|---|---|---|---|
| Lenvatinib | VEGFR1/2/3, FGFR1/2/3/4, PDGFRα, RET, KIT | RAI-refractory thyroid cancer | SELECT (4) | Phase III | PTC (200), FTC (75), OTC (70), PDTC (47) | 64.8% | 18.3 months (lenvatinib) vs. 3.6 months (placebo) |
| Sorafenib | VEGFR1/2/3, RET, RAF, PDGFRβ, KIT | RAI-refractory thyroid cancer | DECISION (5) | Phase III | PTC (237), FTC (106), PDTC (40), WDC (3) | 12.2% | 10.8 months (sorafenib) vs. 5.8 months (placebo) |
| Cabozantinib | VEGFR1/2/3, RET, MET, FLT3, KIT | DTC failing prior anti-VEGF therapy | COSMIC-311 (6) | Phase III | PTC (102), FTC (90) | 15% | Not reached (cabozantinib) vs. 1.9 months (placebo) |
| MTC | EXAM (7) | Phase III | MTC (330) | 28% | 11.2 months (cabozantinib) vs. 4.0 months (placebo) | ||
| Vandetanib | VEGFR1/2/3, RET, EGFR | MTC | ZETA (8) | Phase III | MTC (331) | 45% | Not reached (vandetanib) vs. 19.3 months (placebo) |
| Dabrafenib, trametinib | BRAF (dabrafenib), MEK (trametinib) | BRAF V600E-mutant solid tumors** | ROAR/ BRF117019 (9) | Phase II | ATC (36) | 56% | 6.7 months |
| Selpercatinib | RET | RET fusion+ solid tumors** | LIBRETTO-001 (10) | Phase I/II | PTC (13), PDTC (3), ATC (2), OTC (1) | 79% | 20.1 months |
| RET-mutant MTC | LIBRETTO-001 (10) | Phase I/II | MTC (55 with and 88 without prior MKI treatment) | 69%, 73% | Not reached (previously treated with MKI); 23.6 months (MKI-naïve) | ||
| Pralsetinib | RET | RET fusion+ thyroid cancer | ARROW (11) | Phase I/II | RET fusion-positive thyroid cancer (11) | 89% | Not reached |
| RET-mutant MTC | ARROW (11) | Phase I/II | 55 with and 21 without prior MKI treatment | 60%, 71% | Not reached | ||
| Larotrectinib | NTRK1/2/3 | NTRK fusion+ solid tumors** | NAVIGATE, SCOUT, LOXO-TRK-14001 (12) | Phase I/II | PTC (20), ATC (7), FTC (2) | 71% | 2.2 months for ATC; not reached for other histologic types |
| Entrectinib | NTRK1/2/3, ROS1, ALK | NTRK fusion+ solid tumors** | ALKA-372–001, STARTRK-1, STARTRK-2 (13) | Phase I/II | NTRK fusion-positive thyroid cancer (5) | 20% | - |
ORR objective response rate, PFS progression-free survival, RAI radioactive iodine, DTC diferentiated thyroid carcinoma, PTC papillary thyroid carcinoma, FTC follicular thyroid carcinoma, PDTC poorly diferentiated thyroid carcinoma, WDC well-diferentiated carcinoma, OTC oncocytic thyroid carcinoma, ATC anaplastic thyroid carcinoma, MTC medullary thyroid carcinoma, MKI multi-kinase inhibitors vandetanib and cabozantinib
**
Histology-agnostic approval