PMID- 31931920 OWN - NLM STAT- MEDLINE DCOM- 20201013 LR - 20240328 IS - 2046-4924 (Electronic) IS - 1366-5278 (Print) IS - 1366-5278 (Linking) VI - 24 IP - 2 DP - 2020 Jan TI - Lenvatinib and sorafenib for differentiated thyroid cancer after radioactive iodine: a systematic review and economic evaluation. PG - 1-180 LID - 10.3310/hta24020 [doi] AB - BACKGROUND: Thyroid cancer is a rare cancer, accounting for only 1% of all malignancies in England and Wales. Differentiated thyroid cancer (DTC) accounts for approximately 94% of all thyroid cancers. Patients with DTC often require treatment with radioactive iodine. Treatment for DTC that is refractory to radioactive iodine [radioactive iodine-refractory DTC (RR-DTC)] is often limited to best supportive care (BSC). OBJECTIVES: We aimed to assess the clinical effectiveness and cost-effectiveness of lenvatinib (Lenvima((R)); Eisai Ltd, Hertfordshire, UK) and sorafenib (Nexar((R)); Bayer HealthCare, Leverkusen, Germany) for the treatment of patients with RR-DTC. DATA SOURCES: EMBASE, MEDLINE, PubMed, The Cochrane Library and EconLit were searched (date range 1999 to 10 January 2017; searched on 10 January 2017). The bibliographies of retrieved citations were also examined. REVIEW METHODS: We searched for randomised controlled trials (RCTs), systematic reviews, prospective observational studies and economic evaluations of lenvatinib or sorafenib. In the absence of relevant economic evaluations, we constructed a de novo economic model to compare the cost-effectiveness of lenvatinib and sorafenib with that of BSC. RESULTS: Two RCTs were identified: SELECT (Study of [E7080] LEnvatinib in 131I-refractory differentiated Cancer of the Thyroid) and DECISION (StuDy of sorafEnib in loCally advanced or metastatIc patientS with radioactive Iodine-refractory thyrOid caNcer). Lenvatinib and sorafenib were both reported to improve median progression-free survival (PFS) compared with placebo: 18.3 months (lenvatinib) vs. 3.6 months (placebo) and 10.8 months (sorafenib) vs. 5.8 months (placebo). Patient crossover was high (>/= 75%) in both trials, confounding estimates of overall survival (OS). Using OS data adjusted for crossover, trial authors reported a statistically significant improvement in OS for patients treated with lenvatinib compared with those given placebo (SELECT) but not for patients treated with sorafenib compared with those given placebo (DECISION). Both lenvatinib and sorafenib increased the incidence of adverse events (AEs), and dose reductions were required (for > 60% of patients). The results from nine prospective observational studies and 13 systematic reviews of lenvatinib or sorafenib were broadly comparable to those from the RCTs. Health-related quality-of-life (HRQoL) data were collected only in DECISION. We considered the feasibility of comparing lenvatinib with sorafenib via an indirect comparison but concluded that this would not be appropriate because of differences in trial and participant characteristics, risk profiles of the participants in the placebo arms and because the proportional hazard assumption was violated for five of the six survival outcomes available from the trials. In the base-case economic analysis, using list prices only, the cost-effectiveness comparison of lenvatinib versus BSC yields an incremental cost-effectiveness ratio (ICER) per quality-adjusted life-year (QALY) gained of pound65,872, and the comparison of sorafenib versus BSC yields an ICER of pound85,644 per QALY gained. The deterministic sensitivity analyses show that none of the variations lowered the base-case ICERs to < pound50,000 per QALY gained. LIMITATIONS: We consider that it is not possible to compare the clinical effectiveness or cost-effectiveness of lenvatinib and sorafenib. CONCLUSIONS: Compared with placebo/BSC, treatment with lenvatinib or sorafenib results in an improvement in PFS, objective tumour response rate and possibly OS, but dose modifications were required to treat AEs. Both treatments exhibit estimated ICERs of > pound50,000 per QALY gained. Further research should include examination of the effects of lenvatinib, sorafenib and BSC (including HRQoL) for both symptomatic and asymptomatic patients, and the positioning of treatments in the treatment pathway. STUDY REGISTRATION: This study is registered as PROSPERO CRD42017055516. FUNDING: The National Institute for Health Research Health Technology Assessment programme. FAU - Fleeman, Nigel AU - Fleeman N AD - Liverpool Reviews and Implementation Group, University of Liverpool, Liverpool, UK. FAU - Houten, Rachel AU - Houten R AD - Liverpool Reviews and Implementation Group, University of Liverpool, Liverpool, UK. FAU - Bagust, Adrian AU - Bagust A AD - Liverpool Reviews and Implementation Group, University of Liverpool, Liverpool, UK. FAU - Richardson, Marty AU - Richardson M AD - Liverpool Reviews and Implementation Group, University of Liverpool, Liverpool, UK. FAU - Beale, Sophie AU - Beale S AD - Liverpool Reviews and Implementation Group, University of Liverpool, Liverpool, UK. FAU - Boland, Angela AU - Boland A AD - Liverpool Reviews and Implementation Group, University of Liverpool, Liverpool, UK. FAU - Dundar, Yenal AU - Dundar Y AD - Liverpool Reviews and Implementation Group, University of Liverpool, Liverpool, UK. FAU - Greenhalgh, Janette AU - Greenhalgh J AD - Liverpool Reviews and Implementation Group, University of Liverpool, Liverpool, UK. FAU - Hounsome, Juliet AU - Hounsome J AD - Liverpool Reviews and Implementation Group, University of Liverpool, Liverpool, UK. FAU - Duarte, Rui AU - Duarte R AD - Liverpool Reviews and Implementation Group, University of Liverpool, Liverpool, UK. FAU - Shenoy, Aditya AU - Shenoy A AD - The Clatterbridge Cancer Centre NHS Foundation Trust, Birkenhead, UK. LA - eng GR - DH_/Department of Health/United Kingdom PT - Research Support, Non-U.S. Gov't PT - Systematic Review PL - England TA - Health Technol Assess JT - Health technology assessment (Winchester, England) JID - 9706284 RN - 0 (Antineoplastic Agents) RN - 0 (Iodine Radioisotopes) RN - 0 (Iodine-131) RN - 0 (Phenylurea Compounds) RN - 0 (Quinolines) RN - 9ZOQ3TZI87 (Sorafenib) RN - EE083865G2 (lenvatinib) SB - IM MH - Antineoplastic Agents/*therapeutic use MH - *Cost-Benefit Analysis MH - Humans MH - Iodine Radioisotopes/therapeutic use MH - Phenylurea Compounds/*therapeutic use MH - Quality-Adjusted Life Years MH - Quinolines/*therapeutic use MH - Sorafenib/*therapeutic use MH - Technology Assessment, Biomedical MH - Thyroid Neoplasms/*drug therapy MH - United Kingdom PMC - PMC6983913 OAB - WHAT WAS THE PROBLEM? Differentiated thyroid cancer is a common type of thyroid cancer. For many patients, radioactive iodine is an effective treatment; however, for some patients, the treatment stops working or becomes unsafe. Two new drugs, lenvatinib (Lenvima((R)); Eisai Ltd, Hertfordshire, UK) and sorafenib (Nexar((R)); Bayer HealthCare, Leverkusen, Germany), may be new treatment options. WHAT DID WE DO? We reviewed the clinical evidence of lenvatinib and sorafenib. We also estimated the costs and benefits of treatment. WHAT DID WE FIND? Compared with no treatment, treatment with lenvatinib or sorafenib may increase the time that people live with thyroid cancer before their disease gets worse; however, both drugs are expensive and may have unpleasant side effects. WHAT DOES THIS MEAN? At their published (undiscounted) prices, lenvatinib or sorafenib may not be considered to provide good value for money to the NHS. OABL- eng OTO - NOTNLM OT - IODINE RADIOISOTOPES OT - LENVATINIB OT - MODELS, ECONOMIC OT - SORAFENIB OT - SYSTEMATIC REVIEW OT - THERAPEUTIC USE OT - THYROID NEOPLASMS COIS- No competing interests were declared. EDAT- 2020/01/15 06:00 MHDA- 2020/10/21 06:00 PMCR- 2020/01/27 CRDT- 2020/01/15 06:00 PHST- 2020/01/15 06:00 [entrez] PHST- 2020/01/15 06:00 [pubmed] PHST- 2020/10/21 06:00 [medline] PHST- 2020/01/27 00:00 [pmc-release] AID - 10.3310/hta24020 [doi] PST - ppublish SO - Health Technol Assess. 2020 Jan;24(2):1-180. doi: 10.3310/hta24020.