A systematic review of lenvatinib and sorafenib for treating progressive, locally advanced or metastatic, differentiated thyroid cancer after treatment with radioactive iodine

Abstract

BackgroundTreatment with radioactive iodine is effective for many patients with progressive, locally advanced or metastatic, differentiated thyroid cancer. However, some patients become refractory to treatment. These types of patients are considered to have radioactive iodine refractory differentiated thyroid cancer (RR-DTC).MethodsWe searched Embase, MEDLINE, PubMed and the Cochrane Library from January 1999 through January 2017. Reference lists of included studies and ongoing trial registries were also searched. Reports of randomized controlled trials (RCTs), prospective observational studies, and systematic reviews/indirect comparisons were eligible for inclusion. In the absence of direct clinical trial evidence comparing lenvatinib versus sorafenib, we assessed the feasibility of conducting an indirect comparison to obtain estimates of the relative efficacy and safety of these two treatments.ResultsOf 2364 citations, in total, 93 papers reporting on 2 RCTs (primary evidence), 9 observational studies and 13 evidence reviews (supporting evidence) were identified. Compared to placebo, RCT evidence demonstrated improvements with lenvatinib or sorafenib in median progression-free survival (PFS) and objective tumour response rate (ORR). Overall survival (OS) was confounded by high treatment crossover (≥75%) in both trials. Adverse events (AEs) were more common with lenvatinib or sorafenib than with placebo but the most common AEs associated with each drug differed. Primarily due to differences in the survival risk profiles of patients in the placebo arms of the RCTs, we considered it inappropriate to indirectly compare the effectiveness of lenvatinib versus sorafenib. ORR and AE findings for lenvatinib and sorafenib from the supporting evidence were broadly in line with RCT evidence. Health-related quality of life (HRQoL) data were limited.ConclusionsLenvatinib and sorafenib are more efficacious than placebo (a proxy for best supportive care) for treating RR-DTC. Uncertainty surrounds the extent of the impact on OS and HRQoL. Lenvatinib could not reliably be compared with sorafenib. Choice of treatment is therefore likely to depend on an individual patient’s circumstances.

Complete response to larotrectinib treatment in a patient with papillary thyroid cancer harboring an ETV6‐NTRK3 gene fusion

“…MKIs block kinase receptors involved in angiogenesis (vascular endothelial growth factor receptor and platelet-derived growth factor receptor) and downstream cell survival and proliferation (fibroblast growth factor receptor and proto-oncogene tyrosine-protein kinase receptor Ret [RET]) via the RTK/BRAF/MAPK/ERK and PI3K/AKT/ mTOR pathways. 18 MKIs, such as sorafenib and lenvatinib, are now used routinely in clinical practice for patients who are RAI-R. 8,11,[19][20][21][22][23][24][25] However, their toxicity and the small but significant subset of patients (including the patient described in this report) who do not benefit from MKIs highlight the need for more effective systemic therapies for RAI-R DTC. 12,20,[26][27][28]…”

“…Larotrectinib is typically well tolerated, with few dose modifications required in an analysis of 260 patients 14 . This contrasts with sorafenib and lenvatinib; their use in thyroid cancer may be limited by a high frequency of adverse events 11,19,20 …”

“…14 This contrasts with sorafenib and lenvatinib; their use in thyroid cancer may be limited by a high frequency of adverse events. 11,19,20 Larotrectinib has been evaluated across 15 tumor types in 159 patients with TRK fusion cancer, and the overall response rate (ORR) to larotrectinib was reported as 79%. 14 In patients with TRK fusion thyroid cancer who have undergone multiple rounds of prior therapy, larotrectinib has elicited response rates of approximately 80% and a median progression-free survival of 24.6 months across papillary, follicular, and anaplastic subtypes.…”

Thyroid and COVID-19: a review on pathophysiological, clinical and organizational aspects

“…Target therapies, including multikinase inhibitors and mammalian target of rapamycin inhibitors, have a role in treating advanced thyroid cancers [95][96][97][98][99][100]. Some kinase inhibitors, including sorafenib, sunitinib, and vandetanib, were used against other viral agents, including coronaviruses, and their efficacy as therapeutic instruments in COVID-19 are currently under investigation [101].…”

Lenvatinib and sorafenib for differentiated thyroid cancer after radioactive iodine: a systematic review and economic evaluation

“…FIGURE 6 Comparison of PFS in the placebo arms of DECISION and SELECT. Reproduced with permission from Fleeman et al54 This is an Open Access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY 4.0) license, which permits others to distribute, remix, adapt and build upon this work, for commercial use, provided the original work is properly cited. See: http://creativecommons.org/licenses/by/4.0/.…”