Journal Article

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

Fleeman, Nigel, Duarte, Rui, Beale, Sophie, Shenoy, Aditya, Greenhalgh, Janette, Chaplin, Marty, Boland, Angela, Dundar, Yenal, Houten, Rachel

2019

Overview

Background Treatment 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). Methods We 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. Results Of 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. Conclusions Lenvatinib 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.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Analysis / Antineoplastic agents / Antineoplastic Combined Chemotherapy Protocols - therapeutic use / Biomedical and Life Sciences / Biomedicine / Cancer metastasis / Cancer patients / Cancer Research / Cancer therapies / Clinical effectiveness / Clinical trials / Clinical Trials as Topic / Disease Progression / Drug therapy / Health Promotion and Disease Prevention / Hemorrhage / Humans / Hypertension / Inhibitor drugs / Iodine / Iodine Radioisotopes - therapeutic use / Lenvatinib / Licenses / Medical and radiation oncology / Medicine/Public Health / Meta-Analysis as Topic / Metastases / Metastasis / Neoplasm Metastasis / Neoplasm Staging / Oncology / Patients / Pharmaceutical industry / Phenols (Class of compounds) / Phenylurea Compounds - administration & dosage / Proxy / Quality of life / Quinolines - administration & dosage / Radiotherapy / Randomized Controlled Trials as Topic / Regulatory agencies / Research Article / Sorafenib / Sorafenib - administration & dosage / Studies / Surgical Oncology / Survival / Systematic review / Targeted cancer therapy / Thyroid cancer / Thyroid diseases / Thyroid Neoplasms - drug therapy / Thyroid Neoplasms - pathology / Thyroid Neoplasms - radiotherapy / Treatment Outcome / Tumors / Tyrosine / Tyrosine kinase inhibitor