Table 1.
Phase II and phase III trials of lenvatinib and sorafenib for RAI-refractory DTC.
| Drug | Phase | Study population | N | Main outcomes | Reference |
|---|---|---|---|---|---|
| Lenvatinib | III | Patients with RAI-refractory DTC with radiographic evidence of disease progression within the prior 12 months | 392 | Estimated completion date February 2015 | [ClinicalTrials.gov identifier: NCT01761266] |
| II | Patients with advanced, RAI-refractory DTC and disease progression during the prior 12 months | 58 | PR: 50% (n = 29) | [Sherman et al. 2011] | |
| SD: NR | |||||
| mPFS: 12.6 months | |||||
| Sorafenib | III | Patients with locally advanced/metastatic RAI-refractory DTC with evidence of disease progression within prior 14 months (RECIST) | 417 | mPFS: | [Brose et al. 2013b; Bayer Healthcare Pharmaceuticals] |
| Sorafenib, 10.8 months (95% CI 9.1–12.9) | |||||
| Placebo, 5.8 months (95% CI 5.3–7.8) p < 0.001 | |||||
| DCR (CR + PR + SD ≥6 months): | |||||
| Sorafenib, 54% (n = 106) | |||||
| Placebo, 34% (n = 68) p < 0.0001 | |||||
| II | Patients with metastatic or unresectable thyroid cancer for which curative measures were no longer effective. Evidence of disease progression in the prior 12 months | 30 | PR: 23% (n = 7) | [Gupta-Abramson et al. 2008] | |
| SD: 53% (n = 16)* | |||||
| mPFS: 84 weeks$ | |||||
| II | Metastatic thyroid cancer patients who had experienced I-131 therapy failure or were not candidates to receive I-131 | 52‡ | PR: 12% (n = 6) | [Kloos et al. 2009] | |
| SD: 65% (n = 34) | |||||
| mPFS: PTC (no prior chemo): 16 months | |||||
| PTC (prior chemo): 10 months | |||||
| FTC/HTC: 4.5 months | |||||
| II | Patients with progressive metastases or unresectable local recurrence of DTC for which RAI therapy was no longer effective | 31 | PR: 31% (n = 8) | [Schneider et al. 2012] | |
| SD: 12% (n = 3) | |||||
| mPFS: 18 months | |||||
| II | Patients with progressive locally advanced/metastatic MTC, or DTC with nonradioiodine-avid disease | 19§ | PR: 18% at 1 year | [Ahmed et al. 2011] | |
| 1-year PFS: 68% | |||||
| II | Patients with progressing advanced, iodine-refractory differentiated TC or PDTC, and MTC and ATC | 55 | PR: 38% (n = 18) | [Keefe et al. 2011] | |
| (47 DTC/PDTC, 5 ATC, 3 MTC) | SD: 47% (n = 22) | ||||
| PFS in DTC/PDTC patients: 96 weeks (95% CI 75.1–135.4) | |||||
| OS in DTC/PDTC patients: 140.9 weeks (95% CI 93.9-) | |||||
| II | Patients with progressive metastatic or locally advanced RAI refractory DTC | 31 | PR: 25% (n = 8)SD: 34% (n = 11)PFS: 58 weeks (95% CI 47–68) | [Hoftijzer et al. 2009] |
Includes one patient with MTC who had SD.
Median PFS for patients with DTC.
Excludes four patients with ATC.
Data reported for 19 patients with DTC.
ATC, anaplastic thyroid cancer; CI, confidence interval; CR, complete response; DCR, disease control rate; DTC, differentiated thyroid cancer; FTC, follicular thyroid cancer; HTC, Hürthle cell thyroid cancer; mPFS, median progression-free survival; MTC, medullary thyroid cancer; NR, not reported; OS, overall survival; PDTC, poorly differentiated thyroid cancer; PFS, progression-free survival; PR, partial response; PTC, papillary thyroid cancer; RAI, radioactive iodine; RECIST, Response Evaluation Criteria In Solid Tumors; SD, stable disease; TC, thyroid cancer.