Table 2.
Additional phase II trials of targeted systemic agents in RAI-refractory DTC.
| Drug | Study population | N* | Main outcomes | Reference |
|---|---|---|---|---|
| Axitinib | Patients with advanced thyroid cancer of any histology for whom RAI was not effective or not appropriate | 45 | mPFS: 18.1 months | [Cohen et al. 2008b] |
| PR: 30% (n = 18) | ||||
| SD: 38% (n = 23) | ||||
| Gefitinib | Patients with locally advanced or metastatic RAI-refractory DTC or medullary or anaplastic TC | 25 | mPFS: 3.7 months | [Pennell et al. 2008] |
| mOS: 17.5 months | ||||
| PR: 0 | ||||
| SD$: 12% (n = 3) | ||||
| Motesanib | Patients with locally advanced or metastatic DTC with evidence of progression in prior 6 months that is not amenable to EBRT, resection or is RAI-refractory | 93 | mPFS: 40 weeks | [Sherman et al. 2008] |
| PR: 14% (n = 13) | ||||
| SD: 67% (n = 62) | ||||
| Pazopanib | Patients with RAI-refractory DTC with progression in prior 6 months | 37 | mPFS: 11.7 months | [Bible et al. 2010] |
| PR: 49% (n = 18) | ||||
| Selumetinib | Patients with RAI-refractory PDTC and documented progression within the prior 12 months | 32 | mPFS: 32 weeks‡ | [Hayes et al. 2012] |
| PR: 3% (n = 1) | ||||
| SD: 66% (n = 21) | ||||
| Sunitinib | Patients with DTC or MTC refractory to curative treatment with evidence of progression in prior 6 months | 31 | PR: 13% (n = 4) | [Cohen et al. 2008a] |
| SD: 68% (n = 21) | ||||
| Patients with metastatic RAI-refractory WDTC or MTC and evidence of FDG-PET uptake | 33 (26 DTC, 7 MTC) | CR: 3% (n = 1) | [Carr et al. 2010] | |
| PR: 28% (n = 10) | ||||
| SD: 46% (n = 16) | ||||
| Vandetanib | Patients with locally advanced or metastatic DTC or poorly differentiated DTC without an anaplastic component | VAN: 72PLC: 73 | mPFS VAN: 11.1 monthsmPFS PLC: 5.9 monthsPR VAN: 8% (n = 6)PR PLC: 5% (n = 4) | [Leboulleux et al. 2012] |
| Vemurafenib | Patients with metastatic or unresectable RAI-refractory papillary thyroid cancer positive for the BRAF V600 mutation | 51 | VEGFR inhibitor naïve patientsmPFS: 15.6 moPR: 35% (n=9)SD: 23 (n=6)VEGF inhibitor pretreated patientsmPFS: 6.3 moPR: 29% (n=6)SD: 10 (n=2) | [Brose et al. 2013a] |
*
Patients eligible for response assessment.
$
SD after 12 months of treatment.
‡
Includes all patients.
CR, complete response; DTC, differentiated thyroid cancer; EBRT, external beam radiation therapy; FDG-PET, fluorodeoxyglucose positron emission tomography; mOS, median overall survival; mPFS, median progression-free survival; MTC, medullary thyroid cancer; PLC, placebo; PDTC, poorly differentiated thyroid cancer; PR, partial response; RAI, radioactive iodine; SD, stable disease; TC, thyroid cancer; VAN, vandetanib; WDTC, well differentiated thyroid cancer.