Cost-effectiveness of nivolumab versus surveillance for the adjuvant treatment of patients with urothelial carcinoma who are at high risk of recurrence: a US payer perspective.

AIM: To evaluate the cost-effectiveness of adjuvant nivolumab compared with surveillance for the treatment of patients with high-risk muscle-invasive urothelial carcinoma (MIUC) after radical resection from a US healthcare payer perspective and to investigate the impact of alternative modeling approaches on the cost-effectiveness results. MATERIAL AND METHODS: A four-state, semi-Markov model consisting of disease free, local recurrence, distant recurrence, and death health states was developed to investigate the cost-effectiveness of nivolumab compared with surveillance over a 30-year time horizon. The model used data from the randomized CheckMate 274 trial (NCT02632409) and published literature to inform transitions among health states, and inputs on cost, utility, adverse event, and disease management. Scenario analyses were conducted to investigate the impact of model structure and key assumptions on the results. One-way deterministic and probabilistic sensitivity analysis were conducted to investigate the robustness of the results. RESULTS: Total expected costs were higher with nivolumab ($162,278) compared with surveillance ($63,027). Nivolumab was associated with improved survival (1.61 life-years gained compared with surveillance) and an incremental gain of 0.98 quality-adjusted life-years (QALYs). Although total treatment costs were higher for nivolumab, cost offsets were observed because of delayed or avoided recurrences and deaths experienced with nivolumab compared with observation. The incremental cost-effectiveness and cost-utility ratios were $61,462/life-year and $100,930/QALY. LIMITATIONS: At the time of analysis, CheckMate 274 had limited follow-up on disease-free survival and no overall survival data. The limited evidence necessitated assumptions on modeling survival after each type of recurrence. CONCLUSIONS: Nivolumab is estimated to be a life-extending and cost-effective option for adjuvant treatment of MIUC for patients who are at high risk of recurrence after undergoing radical resection in the United States. Using a threshold of $150,000/QALY, the cost-effectiveness conclusions remained consistent across the scenario and sensitivity analyses conducted.

Challenges, considerations, and approaches for developing a cost-effectiveness model for the adjuvant treatment of muscle-invasive urothelial carcinoma: with a spotlight on nivolumab versus placebo.

AIMS: To present alternative approaches related to both structural assumptions and data sources for the development of a decision analytic model for evaluating the cost-effectiveness of adjuvant nivolumab compared with surveillance in patients with high-risk muscle-invasive urothelial carcinoma (MIUC) after radical resection. METHODS AND RESULTS: Alternative approaches related to both structural assumptions and data sources are presented to address challenges and data gaps, as well as discussion of strengths and limitations of each approach. Specifically, challenges and considerations related to the following are presented: (1) selection of a modeling approach (partitioned survival model or state transition model) given the available evidence, (2) choice of health state structure (three- or four-state) to model disease progression and subsequent therapy, (3) modeling of outcomes from subsequent therapy using tunnel states to account for time-dependent transition probabilities or absorbing health states with one-off costs and outcomes applied, and (4) methods for modeling health-state transitions in a setting where treatment has curative intent and available survival data are immature. CONCLUSIONS: Multiple considerations must be taken into account when developing an economic model for new, emerging oncology treatments in early lines of therapy, all of which can affect the model's overall ability to estimate (quality-adjusted) survival benefits over a lifetime horizon. This paper identifies a series of key structural and analytic considerations regarding modeling of nivolumab treatment in the adjuvant MIUC setting. Several alternative approaches with regard to structure and data have been included in a flexible cost-effectiveness model so the impact of the alternative approaches on model results can be explored. The impact of these alternative approaches on cost-effectiveness results are presented in a companion article. Our findings may also help inform the development of future models for other treatments and settings in early-stage cancer.

Cost-Utility Analysis of Nivolumab in Adjuvant Treatment of Melanoma in France.

INTRODUCTION: The aim of the current study is to estimate the cost-effectiveness of adjuvant treatment with nivolumab relative to clinically relevant comparators in adult patients with melanoma with lymph node involvement or metastatic disease who have undergone complete resection from a French societal perspective. METHODS: The comparators were observation, low-dose interferon and pembrolizumab. A subgroup analysis was carried out in patients with BRAF mutation, adding dabrafenib plus trametinib. A three-state partitioned survival model was developed to project costs and health benefits over a 20-year time horizon. Extrapolation for recurrence-free survival (RFS) and overall survival (OS) was carried out using spline-based models. Because of the immaturity of OS data in pivotal trials for nivolumab and pembrolizumab, a predictive model of OS treatment effect based on RFS effect was developed using a correlation equation. Health state utilities and adverse events disutilities were derived from the CheckMate 238 trial and literature. Costs were estimated in 2019 euros. The model's primary outcome was efficiency frontier. Deterministic and probabilistic sensitivity analyses were conducted to assess the robustness of results. RESULTS: Observation, low-dose interferon and nivolumab were on the efficiency frontier. The incremental cost-utility ratio of nivolumab versus low-dose interferon (closest therapy on the efficiency frontier) was €37,886/quality-adjusted life year (QALY). Probabilistic sensitivity analysis reported an 80% probability of nivolumab being a cost-effective strategy for a willingness-to-pay threshold of €52,000/QALY. In the subgroup with BRAF mutation, the efficiency frontier was not changed by the addition of dabrafenib plus trametinib. CONCLUSIONS: Nivolumab is a cost-effective strategy as adjuvant treatment in adult patients with surgically resected melanoma in France.

Cross-sectional survey in CKD patients across Europe describing the association between quality of life and anaemia.

BACKGROUND: Deteriorating renal function in chronic kidney disease (CKD) patients is commonly associated with reduced haemoglobin levels, adding to the already considerable humanistic burden of CKD. This analysis evaluated the impact of anaemia on disease burden in patients with CKD stages 3-4, and in those on dialysis. METHODS: This was a descriptive, cross-sectional analysis of European data from an Adelphi CKD Disease-Specific Programme. This programme collected data from patients and their treating nephrologists/endocrinologists; patient- and physician-reported data were matched for each patient. Health-related quality of life (HRQoL) data were obtained through patient completion of the EQ-5D, SF-12 and KDQOL-36. Additional information was obtained via physician reporting of patient symptoms, and patients' reports of impaired activity. Anaemia was defined by haemoglobin level and/or current use of erythropoiesis stimulating agents. RESULTS: Significant, but modest Spearman's rank correlations were observed between haemoglobin levels and extent of HRQoL impairment, regardless of instrument used (range 0.19-0.23; all P-values < 0.0001). When stratified by anaemia status, impairment was consistently lower for anaemic than non-anaemic CKD patients across measurement scales (e.g. EQ-5D index value [standard deviation {SD}] 0.72 [0.31] vs 0.83 [0.23], respectively; P < 0.0001). Physician-reported patient tiredness was associated with increased disease burden at all levels of CKD studied (total EQ-5D index value [SD] in patients reporting no tiredness vs tiredness 0.81 [0.26] vs 0.70 [0.30] respectively; P < 0.0001) with P < 0.0001 for no tiredness vs tiredness at all stages of CKD. The presence of anaemia was associated with impaired activity levels at CKD stages 3 (37.5 % vs 28.4 %, respectively; P = 0.0044) and 4 (48.1 % vs 39.9 %, respectively; P = 0.0292), and in patients on dialysis (52.0 % vs 45.0 %, respectively; P = 0.0732). CONCLUSIONS: The analysis found that CKD patients with anaemia typically had a lower HRQoL than those without anaemia. The impairment correlated with anaemia was more apparent in non-dialysis patients with CKD stages 3 or 4 than in those receiving dialysis. Coexisting CKD and anaemia may have an impact on patient HRQoL similar to other chronic conditions such as diabetes, epilepsy or certain forms of cancer.