Efficacy and toxicity of sorafenib in the treatment of advanced medullary thyroid carcinoma: A systematic review and meta‐analysis

Abstract

Introduction The aim of this study is to investigate and summarize the treatment efficacy and adverse effects (AEs) of sorafenib in the treatment of metastatic medullary thyroid carcinomas (MTCs). Methods We included studies reporting the treatment efficacy or drug toxicity of sorafenib as a single therapeutic agent in MTCs. Pooled incidence and its 95% confidence interval (CI) for complete response, partial response (PR), stable disease (SD), and sorafenib‐related AEs were calculated using random‐effect model. Results Eight trials with 101 metastatic MTCs were included for meta‐analyses. The overall PR and SD were 21% (95% CI = 9‐33) and 58% (95% CI = 41‐75), respectively. Hand‐foot syndrome, diarrhea, alopecia, mucositis, skin rash, fatigue, and hypertension were the most commonly observed AEs. Conclusion Our results show that sorafenib treatment has a modest effect and might be a candidate treatment in patients with metastatic MTCs who have failed other therapeutic regimens.

Thyroid Carcinoma, Version 2.2022, NCCN Clinical Practice Guidelines in Oncology

“…Other small-molecule kinase inhibitors (ie, sorafenib, sunitinib, lenvatinib, pazopanib) may be considered if clinical trials or the NCCN-preferred systemic therapy options are not available or are not appropriate. [125][126][127][128][129][130][131] If the patient progresses on a preferred option, then systemic chemotherapy can be administered using dacarbazine or combinations including dacarbazine. 66,[132][133][134] Pembrolizumab is also an option for patients with TMB-H ($10 mut/Mb) disease (useful in certain circumstances).…”

Therapeutic peptides: current applications and future directions

“…The clinical use of small molecules is also limited by their low specificity compared with peptide drugs. For example, sorafenib and sunitinib are tyrosine kinase inhibitors that inhibit the tyrosine kinase domain activity of vascular endothelial growth factor (VEGF) receptors, resulting in anti-angiogenic effects that are used to treat cancer patients [39][40][41] ; however, they also target other kinase receptors such as serine/threonine kinase receptors, leading to cytotoxicity [42][43][44][45][46] .…”

Metastatic medullary thyroid carcinoma: a new way forward

“…In two meta-analyses including 101 and 99 progressive MTC patients, respectively, from 8 studies using sorafenib as the single TKI treatment (previous treatments included surgery, chemotherapy or radiotherapy), sorafenib showed an intermediate efficacy. In the first meta-analysis, an overall partial response and stable disease were found in 21 and 58% of MTC patients, respectively ( Vuong et al 2019 ), while in the other, an objective response (including complete and partial responses) was found in 27.6% of patients with a PFS of 12.4 months (95% CI: 8.4–16). However, this was associated with a high discontinuation rate of up to 32.3% (95% CI: 24.3–40) of patients due to toxicity ( Vuong et al 2019 , Efstathiadou et al 2021 ).…”

“…In the first meta-analysis, an overall partial response and stable disease were found in 21 and 58% of MTC patients, respectively ( Vuong et al 2019 ), while in the other, an objective response (including complete and partial responses) was found in 27.6% of patients with a PFS of 12.4 months (95% CI: 8.4–16). However, this was associated with a high discontinuation rate of up to 32.3% (95% CI: 24.3–40) of patients due to toxicity ( Vuong et al 2019 , Efstathiadou et al 2021 ). Responses to sorafenib were not durable, with resistance developing, usually within 1–2 years ( Vuong et al 2019 ).…”

“…However, this was associated with a high discontinuation rate of up to 32.3% (95% CI: 24.3–40) of patients due to toxicity ( Vuong et al 2019 , Efstathiadou et al 2021 ). Responses to sorafenib were not durable, with resistance developing, usually within 1–2 years ( Vuong et al 2019 ).…”