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New HTA Decisions in Scotland
June 2020
Drug name
KISPLYX® (lenvatinib)
Eisai Ltd
Decision date
Therapeutic area
Therapeutic sub area
Renal cancer
Recommended (PACE)
In combination with everolimus for the treatment of adult patients with advanced renal cell carcinoma (RCC) following one prior vascular endothelial growth factor (VEGF)-targeted therapy.
Decision Detail
Following a full submission assessed under the end of life and orphan medicine proccess, lenvatinib (Kisplyx®) is accepted for use in NHS Scotland. This SMC advice takes account of the benefit of Patient Access Schemes (PAS) that improve the cost effectiveness of lenvatinib and everolimus. This advice is contingent upon the continuing availability of these PAS in NHS Scotland or list prices that are equivalent or lower. This advijavascript:--doPostBack('ctl00$ContentPlaceHolder1$lnkUpdateitem','')ce takes account of views from a Patient and Clinician Engagement (PACE) meeting.
The evidence to support the use of lenvatinib for this indication comes from one key, open-label, randomised, phase II study (Study 205). The study demonstrated that the addition of lenvatinib to everolimus significantly improved progression-free survival in patients with advanced renal cell carcinoma who had received one previous VEGF-targeted therapy. The company submitted a cost-utility analysis comparing lenvatinib plus everolimus with axitinib, nivolumab and cabozantinib for the treatment of advanced RCC following one prior VEGF-targeted therapy. SMC clinical expert responses indicate that nivolumab and cabozantinib are the treatments most likely to be displaced. A partitioned survival model was used with three health states: pre-progression, post-progression and death. The distribution across the health states was defined by the PFS and overall survival curves, along with time to discontinuation (TTD) curves that define the proportion of patients who are alive and on treatment. A lifetime horizon was used which equated to 20 years. The following limitations were noted: - There are limitations with the clinical data used to estimate the benefit of lenvatinib plus everolimus in the economic model meaning the cost-effectiveness results are uncertain. Study 205 is a phase II study with small patient numbers and did not provide evidence versus a relevant comparator. - There are no direct comparative data comparing lenvatinib plus everolimus with nivolumab, cabozantinib or axitinib, which are the treatments currently used in Scotland. A fractional polynomial NMA was conducted which was associated with limitations as described above. Sensitivity analysis testing the overall survival benefit estimated by the model showed there was some sensitivity to changes in this parameter. - The results of the NMA indicate there is a trend favouring lenvatinib plus everolimus for PFS outcomes but there is no evidence of superiority, particularly for the comparisons with nivolumab and cabozantinib. Given these results, the company was asked to provide a cost-minimisation analysis which assumes there is no difference in efficacy between these treatments. - Sensitivity analysis showed the results of the model were sensitive to using an alternative assumption regarding the treatment duration where patients are treated to progression. The base case analysis used to treat discontinuation data from the relevant studies and then extrapolated these data over the model time horizon. While a small proportion of patients may be treated beyond progression there is uncertainty associted with this aspect of the mode. The company provided additional sensitivity analysis using the CMA where patients assumed to switch treatment at progression and this did not materially affect the conclusions of the CMA. - No post-progression treatment costs were included in the base case analysis, which may not be reflective of the patient pathway. All patients were assumed to receive best supportive care as no treatments are currently licensed for third line use. This was tested in the sensitivity analysis but the results were not overly sensitive to this. The Committee considered the benefits of lenvatinib in the context of the SMC decision modifiers that can be applied when encountering high cost-effectiveness ratios and agreed that as lenvatinib is an orphan equivalent medicine, SMC can accept greater uncertainty in the economic case. After considering all the available evidence and the output from the PACE process, the Committee accepted lenvatinib for use in NHS Scotland.