Table 7.
Phase II-III trials investigated target therapy in all type of TCs.
| Drug | Targets | Study design / ClinicalTrial.gov ID | Enrolled patients and timing | Treatment arm(s) | Results | Reference |
|---|---|---|---|---|---|---|
| Selumetinib | MEK | Pilot study, single arm [NCT00970359] |
Metastatic TC: 20 (enrolled from 08/2010 to 12/2011) | 75 mg selumetinib twice daily. Within 1 month, patients with adequate RAI uptake may receive 131I per standard of care and continue selumetinib until 2 days following 131I. | 12/20 increased the uptake of iodine-124 PR: 5/20 SD: 3/20 |
(87) |
| Phase II, single arm, open label [NCT00559949] | RAI-R PTC: 39 (enrolled from 12/2007 to 06/2009) | 100 mg selumetinib twice daily | PR: 3% SD: 54% PD: 28% mPFS: 32 weeks |
(88) | ||
| Phase III, randomized, double blind (ASTRA) [NCT01843062] |
DTC at high risk of primary treatment failure: 233 (enrolled from 08/2013 to 03/2016) | Selumetinib 75 mg BD + RAI | CR: 40% | (89) | ||
| Pazopanib | VEGFR, PDGF, c-KIT | Phase II [NCT00625846] |
RAI-R DTC: 39 (enrolled from 02/2008 to 01/2009) | 800 mg pazopanib once daily | PRs: 49% FTC PRs: 73% PTC PRs: 33% |
(90) |
| Phase II [NCT00625846] |
RAI-R DTC: 60 | 800 mg pazopanib once daily | PRs: 36.7% | (91) | ||
| Phase II PAZOTHYR [NCT01813136] |
RAI-R TC: 168 (enrolled from 06/2013 to 01/2018) | 800 mg pazopanib once daily (n=100 were randomized 1:1 to receive continuos [CP] vs intermittent [IP] pazopanib treatment) |
IP TTP: 14.7 CP TTP 11.9 (p=0.35) |
(92) | ||
| Phase II, multicenter (enrolled from 09/2008 to 12/2011) [NCT00625846] |
MTC: 35 (enrolled from 09/2008 to 12/2011) | 800 mg pazopanib once daily | PR: 14.3% PFS: 9.4 months OS: 19.9 months |
(93) | ||
| Phase II, multicenter, single arm [NCT01236549] |
ATC: 16 (enrolled from 02/2008 to 02/2011) | 800 mg pazopanib once daily | No confirmed RECIST responses | (71) | ||
| Sunitinib | VEGFR, PDGFR; RET, c-KIT, FLT | Phase II single center, nonrandomized, open-label [NCT00668811] | Advanced DTC: 23 (enrolled from 09/2008 to 02/2015) | 37.5 mg sunitinib once daily | ORR: 26% mPFS: 241 days |
(94) |
| Phase II, single arm, open label (THYSO) [NCT00510640] |
RAI-R DTC, MTC or ATC: 71 [DTC: 41, ATC: 4, MTC: 26] (enrolled from 08/2007 to 10/2009 |
50 mg sunitinib once daily | DTC ORR: 22% MTC ORR: 38.5% ATC ORR : not observed |
(72) | ||
| Phase II, single center |
RAI-R DTC or MTC: 35 [DTC: 28 MTC: 7] (enrolled from 08/2007 to 02/2009) |
37.5 mg sunitinib once daily | ORR: 31% | (95) | ||
| Motesanib | VEGFR 1-3, PDGFR, c-KIT, RET wild type | Phase II, open label [NCT00121628] |
RAI-R DTC: 93 MTC: 91 (enrolled from 07/2005 to 03/2006) |
125 mg motesanib once daily | DTC ORR: 14% DTC SD: 67% (maintained for 6 months in 35% of patients) MTC ORR: 2% MTC SD: 81% MTC durable SD (≥24 weeks): 48% |
(96) (97), |
| Apatinib | VEGFR-2 | Phase II [NCT02731352] | RAI-R DTC: 20 (enrolled from 03/2016 to 02/2021) | 500 or 750 mg apatinib once daily | ORR: 80% DCR: 95% |
(98) (99), |
| Phase III, exploratory, randomized, double arms [NCT03048877] | RAI-R DTC: 92 (enrolled from 09/2017 to 08/2020) | 500 mg apatinib once daily vs placebo | mPFS: 22.2 months | (100) | ||
| Axitinib | VEGFR | Phase II [NCT00389441] | RAI-R DTC or MTC : 52 (enrolled from 12/2006 to 09/2008) | 5 mg axitinib twice daily | ORR: 35% | (101) |
| Phase II, single arm [NCT00094055] |
RAI-R TC: 60 [DTC: 45 MTC: 11 ATC: 2 Other: 2] |
5 mg axitinib twice daily | ORR: 30% PFS: 18.1 months [MTC PRs: 18% MTC SD: 27%] |
(73) (74), | ||
| RAI-R DTC or MTC: 47 (enrolled from 10/2012 to 11/2014) | 5 mg axitinib twice daily | mORR: 27,7% (DTC ORR:29.4%; MTC ORR: 23.1%) | (102) | |||
| Donafenib | VEGFR, PDGFR, RAF | Phase II [NCT02870569] | RAI-R DTC: 35 | 300 mg donafenib twice daily (17) or 200 mg twice daily (18) | 200 mg group ORR: 12.5% 300 mg group ORR: 13.33% | (103) |
| Phase III, randomized [NCT03602495] | RAI-R DTC: 204 | Patients were randomized 2:1 to receive 300 mg donafenib twice daily vs placebo | N/A | |||
| Dovitinib | VEGFR, FGFR | Phase II | TC: 40 [DTC: 28; MTC: 12] (enrolled from 01/2013 to 10/2014) | Dovitinib 500 mg once daily for five consecutive days, followed by a 2-day rest every week | ORR: 20.5% PFS: 5.4 months OS not reached |
(104) |
ATC, anaplastic thyroid cancer; c-KIT, stem cell factor receptor; CR, complete response; DTC, differentiated thyroid cancer; FGFR, fibroblast growth factor receptor; MTC, medullary thyroid cancer; N/A, not reported; ORR, objective response rate; OS, overall survival; PDGFR, platelet-derived growth factor receptor; PFS, progression-free survival; PD, progressive disease; PRs, partial responses; RAF, rapidly accelerated fibrosarcoma; RAI-R, resistant to 131I treatment; RECIST, response evaluation criteria in solid tumors; RET, rearranged during transfection receptor; TTP, time to treatment failure; VEGFR, vascular endothelial growth factor.