Treatments for renal cell carcinoma: NICE Pilot Treatment Pathways Appraisal.

Background: The National Institute for Health and Care Excellence is piloting a new approach to evaluating health technologies, which takes into consideration the full treatment pathway for a condition. This report describes the first pilot topic for the pathways process, which evaluated systemic treatments for advanced renal cell carcinoma. Objectives: This pilot aimed to develop a decision model representing the treatment pathway that will be used to evaluate new technologies for advanced renal cell carcinoma. The pilot also evaluated a new treatment for renal cell carcinoma: cabozantinib (Cabometyx®; Ipsen, Slough, UK) plus nivolumab (Opdivo®; Bristol Myers Squibb, Princeton, NJ, USA). Review methods: A systematic literature review was conducted to identify evidence to inform effectiveness, safety and economic model development, including systematic literature reviews, randomised controlled trials, economic evaluations, utility studies and cost and resource use data. Real-world evidence was sought following the recommendations of the National Institute for Health and Care Excellence real-world evidence framework. Structured expert elicitation informed assumptions about overall survival and progression-free survival. Network meta-analyses were conducted to evaluate the clinical effectiveness of treatments. A de novo state transition model that was constructed with a partitioned survival analysis structure was also presented. The cost perspective of the model was that of the National Health Service and Personal Social Services; the time horizon was 40 years, costs and outcomes were discounted at 3.5% per annum and a 2022 price year was used. The model allowed sequences of up to four active lines of treatment. Information sources: The review included 118 systematic literature reviews, 30 randomised controlled trials, 122 economic evaluations, 82 studies reporting utility data and 13 studies reporting cost and/or resource use data. A total of 21 real-world evidence sources were identified. Unpublished data were provided by the manufacturer and other stakeholders (competitor companies, patient and clinical organisations). The expert elicitation recruited nine United Kingdom-based oncologists. Results: Cabozantinib plus nivolumab was associated with better progression-free survival and overall survival than existing tyrosine kinase inhibitors as first-line treatment in the all-risk group. Using the list price of the evaluated interventions, the incremental cost-effectiveness ratio for cabozantinib plus nivolumab compared to the next non-dominated tyrosine kinase inhibitor monotherapy (pazopanib [Votrient®; Novartis, Slough, UK]) was £275,106 per quality-adjusted life-year in the all-risk population and was £379,222 in the favourable-risk population. Incremental cost-effectiveness ratios were relatively consistent across the base-case and scenario analyses. In the intermediate-/poor-risk population, the incremental cost-effectiveness ratio for pembrolizumab (Keytruda®; Merck Sharp & Dohme, London, UK) plus lenvatinib (Lenvima®; Eisai, Hatfield, UK) was £450,638 compared to cabozantinib; cabozantinib plus nivolumab and nivolumab plus ipilimumab were both dominated by cabozantinib and pazopanib monotherapy, respectively, in the base-case analysis. Quality-adjusted life-year gains were similar for cabozantinib plus nivolumab, pembrolizumab plus lenvatinib and nivolumab plus ipilimumab (Yervoy®; Bristol-Myers Squibb, Princeton, NJ, USA). Cabozantinib plus nivolumab was shown to be less effective and less expensive than pembrolizumab plus lenvatinib in most scenarios. Limitations: Most interventions were supported by only one trial and data quality was poor. Outcomes reported in clinical trials were generally more favourable than those reported in real-world evidence, suggesting that trials may overestimate treatment benefits. Conclusions: This pilot demonstrated the feasibility of producing a reference model, which is open source and available to relevant stakeholders without restriction. This will improve consistency in the National Institute for Health and Care Excellence's decision-making and allow for the evaluation of optimum treatment sequences for advanced renal cell carcinoma. Future work: Future research is needed to resolve uncertainties in clinical effectiveness estimates for treatments for advanced renal cell carcinoma, including long-term effectiveness of combination treatments and their effectiveness in the favourable-risk subgroup. This would also inform further evaluation of optimal treatment sequences for advanced renal cell carcinoma. This evaluation included the use of confidential data, including commercially sensitive data provided by the manufacturers of treatments for renal cell carcinoma. Where feasible, references to confidential data have been removed from this monograph. Any remaining instances of confidential data have been redacted. Study registration: A final review protocol was submitted to National Institute for Health and Care Excellence in advance. Due to confidentiality issues surrounding the analysis plan, this was not deposited with PROSPERO. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Evidence Synthesis programme (NIHR award ref: NIHR136008) and is published in full in