PMID- 29393024 OWN - NLM STAT- MEDLINE DCOM- 20190409 LR - 20230918 IS - 2046-4924 (Electronic) IS - 1366-5278 (Print) IS - 1366-5278 (Linking) VI - 22 IP - 6 DP - 2018 Jan TI - Axitinib, cabozantinib, everolimus, nivolumab, sunitinib and best supportive care in previously treated renal cell carcinoma: a systematic review and economic evaluation. PG - 1-278 LID - 10.3310/hta22060 [doi] AB - BACKGROUND: Several therapies have recently been approved for use in the NHS for pretreated advanced or metastatic renal cell carcinoma (amRCC), but there is a lack of comparative evidence to guide decisions between them. OBJECTIVE: To evaluate the clinical effectiveness and cost-effectiveness of axitinib (Inlyta((R)), Pfizer Inc., NY, USA), cabozantinib (Cabometyx((R)), Ipsen, Slough, UK), everolimus (Afinitor((R)), Novartis, Basel, Switzerland), nivolumab (Opdivo((R)), Bristol-Myers Squibb, NY, USA), sunitinib (Sutent((R)), Pfizer, Inc., NY, USA) and best supportive care (BSC) for people with amRCC who were previously treated with vascular endothelial growth factor (VEGF)-targeted therapy. DATA SOURCES: A systematic review and mixed-treatment comparison (MTC) of randomised controlled trials (RCTs) and non-RCTs. Primary outcomes were overall survival (OS) and progression-free survival (PFS). Secondary outcomes were objective response rates (ORRs), adverse events (AEs) and health-related quality of life (HRQoL). MEDLINE, EMBASE and The Cochrane Library were searched from inception to January and June 2016 for RCTs and non-RCTs, respectively. Two reviewers abstracted data and performed critical appraisals. REVIEW METHODS: A fixed-effects MTC was conducted for OS, PFS [hazard ratios (HRs)] and ORR (odds ratios), and all were presented with 95% credible intervals (CrIs). The RCT data formed the primary analyses, with non-RCTs and studies rated as being at a high risk of bias included in sensitivity analyses (SAs). HRQoL and AE data were summarised narratively. A partitioned survival model with health states for pre progression, post progression and death was developed to perform a cost-utility analysis. Survival curves were fitted to the PFS and OS results from the MTC. A systematic review of HRQoL was undertaken to identify sources of health state utility values. RESULTS: Four RCTs (n = 2618) and eight non-RCTs (n = 1526) were included. The results show that cabozantinib has longer PFS than everolimus (HR 0.51, 95% CrI 0.41 to 0.63) and both treatments are better than BSC. Both cabozantinib (HR 0.66, 95% CrI 0.53 to 0.82) and nivolumab (HR 0.73, 95% CrI 0.60 to 0.89) have longer OS than everolimus. SAs were consistent with the primary analyses. The economic analysis, using drug list prices, shows that everolimus may be more cost-effective than BSC with an incremental cost-effectiveness ratio (ICER) of pound45,000 per quality-adjusted life-year (QALY), as it is likely to be considered an end-of-life treatment. Cabozantinib has an ICER of pound126,000 per QALY compared with everolimus and is unlikely to be cost-effective. Nivolumab was dominated by cabozantinib (i.e. more costly and less effective) and axitinib was dominated by everolimus. LIMITATIONS: Treatment comparisons were limited by the small number of RCTs. However, the key limitation of the analysis is the absence of the drug prices paid by the NHS, which was a limitation that could not be avoided owing to the confidentiality of discounts given to the NHS. CONCLUSIONS: The RCT evidence suggests that cabozantinib is likely to be the most effective for PFS and OS, closely followed by nivolumab. All treatments appear to delay disease progression and prolong survival compared with BSC, although the results are heterogeneous. The economic analysis shows that at list price everolimus could be recommended as the other drugs are much more expensive with insufficient incremental benefit. The applicability of these findings to the NHS is somewhat limited because existing confidential patient access schemes could not be used in the analysis. Future work using the discounted prices at which these drugs are provided to the NHS would better inform estimates of their relative cost-effectiveness. STUDY REGISTRATION: This study is registered as PROSPERO CRD42016042384. FUNDING: The National Institute for Health Research Health Technology Assessment programme. FAU - Edwards, Steve J AU - Edwards SJ FAU - Wakefield, Victoria AU - Wakefield V FAU - Cain, Peter AU - Cain P FAU - Karner, Charlotta AU - Karner C FAU - Kew, Kayleigh AU - Kew K FAU - Bacelar, Mariana AU - Bacelar M FAU - Masento, Natalie AU - Masento N FAU - Salih, Fatima AU - Salih F LA - eng GR - TAR/16/58/01/DH_/Department of Health/United Kingdom PT - Journal Article PT - Meta-Analysis PT - Research Support, Non-U.S. Gov't PT - Review PT - Systematic Review PL - England TA - Health Technol Assess JT - Health technology assessment (Winchester, England) JID - 9706284 RN - 0 (Anilides) RN - 0 (Antineoplastic Agents) RN - 0 (Pyridines) RN - 0 (Vascular Endothelial Growth Factor A) RN - 1C39JW444G (cabozantinib) RN - 31YO63LBSN (Nivolumab) RN - 9HW64Q8G6G (Everolimus) RN - C9LVQ0YUXG (Axitinib) RN - V99T50803M (Sunitinib) SB - IM MH - Anilides/therapeutic use MH - Antineoplastic Agents/administration & dosage/adverse effects/*economics/*therapeutic use MH - Axitinib/therapeutic use MH - Carcinoma, Renal Cell/*drug therapy MH - Clinical Trials as Topic MH - Cost-Benefit Analysis MH - Everolimus/therapeutic use MH - Humans MH - Kidney Neoplasms/*drug therapy MH - Models, Econometric MH - Nivolumab/therapeutic use MH - Pyridines/therapeutic use MH - Quality-Adjusted Life Years MH - Sunitinib/therapeutic use MH - Technology Assessment, Biomedical MH - Vascular Endothelial Growth Factor A/antagonists & inhibitors PMC - PMC5817410 EDAT- 2018/02/03 06:00 MHDA- 2019/04/10 06:00 PMCR- 2018/02/19 CRDT- 2018/02/03 06:00 PHST- 2018/02/03 06:00 [entrez] PHST- 2018/02/03 06:00 [pubmed] PHST- 2019/04/10 06:00 [medline] PHST- 2018/02/19 00:00 [pmc-release] AID - 10.3310/hta22060 [doi] PST - ppublish SO - Health Technol Assess. 2018 Jan;22(6):1-278. doi: 10.3310/hta22060.