Cost-effectiveness of nivolumab in squamous and non-squamous non-small cell lung cancer in Canada and Sweden: an update with 5-year data

Abstract

Aims: Nivolumab has been approved for advanced squamous and non-squamous non-small cell lung cancer (NSCLC) following platinum-based chemotherapy in both Canada and Sweden. We aimed to determine the value-for-money of nivolumab versus docetaxel in a Canadian and Swedish setting based on 5-year data. Methods: These cost effectiveness analyses used partitioned survival models with three mutually exclusive health states: progression-free, progressed disease, and death. All clinical parameters were derived from two registration phase 3 randomized trials, CheckMate 017 and CheckMate 057, with a minimum follow-up of 5 years. Treatment duration was based on time-on-treatment data from the clinical trials. Costs were derived from published sources. The primary outcomes of the analyses were quality-adjusted life-years (QALYs), life-years gained, and incremental cost-effectiveness ratios (ICERs). The model input parameters for each analysis were chosen in line with guidance from the respective HTA authorities. Results: From a Canadian payer perspective, the ICERs were CAN$140,753 per QALY in the squamous population, and CAN$173,804 per QALY in the non-squamous population, assuming a 10-year time horizon and a 5% discount rate for both costs and outcomes. Sensitivity analyses demonstrated that changes to the discount rates for outcomes had the highest impact on the ICERs. In the Swedish analysis, the ICERs were SEK568,895 per QALY in the squamous population and SEK662,991 per QALY in the non-squamous population, assuming a 15-year time horizon, a 3% discount rate, and a 2-year maximum treatment duration for nivolumab. Sensitivity analyses demonstrated that the ICERs were most sensitive to changes in the discount rate for outcomes. Conclusion: These updated analyses, based on more mature trial data with a minimum follow-up of 5 years, generate more favorable ICERs versus the previously submitted HTA assessments that resulted in approval of nivolumab for patients with previously treated NSCLC in Canada and Sweden.

PD-L1 Test-Based Strategy With Nivolumab as the Second-Line Treatment in Advanced NSCLC： A Cost-Effectiveness Analysis in China

“…From a Chinese healthcare system perspective, our previous cost-effectiveness analysis revealed that second-line nivolumab was unlikely to be cost-effective compared with docetaxel in patients with advanced NSCLC, despite the subgroup analysis showing the improved cost-effectiveness of nivolumab in the patients with PD-L1TPS ≥1% ( 12 ). Although this finding did not concur with the cost-effectiveness analyses conducted in other countries showing a favorable cost-effectiveness of nivolumab versus docetaxel in previously treated advanced NSCLC patients regardless of PD-L1 expression ( 13 , 14 ), different perspectives, trial source used for analysis, and approach to modeling used between these studies have to be highlighted that may explain the inconsistency. Considering that nivolumab is recommended as the preferred second-line treatment for advanced NSCLC patients without ALK or EGFR mutations regardless of their PD-L1 expression in China, evidence regarding the impact of PD-L1 test results on the comparative cost-effectiveness of second-line nivolumab versus docetaxel from a Chinese health system perspective is urgently needed to inform Chinese healthcare policy making.…”

Use of Advanced Flexible Modeling Approaches for Survival Extrapolation from Early Follow-up Data in two Nivolumab Trials in Advanced NSCLC with Extended Follow-up

“…The use of external data is particularly useful when only limited trial follow-up data is available, as they can provide validation of the resulting extrapolations for survival probabilities and hazard rates from short-term data [13]. Such an approach was previously taken in relation to the CheckMate-017 and CheckMate-057 cost-effectiveness models used in HTA submissions, where external validation of parametric models was carried out using NSCLC data from the longer term Phase I trial CheckMate-003, as well as longer term data from the US National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program and the national cancer registries of Sweden and Norway [12,[14][15][16][17][18]. The nivolumab OS parametric models used in these cost-effectiveness models are herein referred to as 'validated SPMs', whereas those that do not leverage external data are referred to as 'non-validated SPMs' for the purpose of this research.…”

“…In this previous work, dependent and independent parametric models were considered by BMS in model selection, although the focus of this paper is restricted to the nivolumab arm. Validated SPMs were those used in cost-effectiveness models submitted to NICE and other HTA bodies and later published in peer-reviewed journals, and were selected conservatively to avoid criticism by the ERG and other HTA reviewers [14][15][16][17][18].…”

“…Independent models were fitted separately to each treatment arm, and dependent models included treatment effect as a covariate on the location parameter, although in the present work we are concerned only with the estimated SPMs for the nivolumab arm. ERG SPMs for the 2-and 3-year data cuts were recreated by applying the model assumptions proposed by the NICE ERG during nivolumab assessments for second-line treatment in advanced NSCLC, which pertained to 24-and 18month DBLs for CheckMate-017 and -057, respectively [14][15][16][17][18]. In these appraisals, the ERG proposed a hybrid exponential model combining KM estimates up to 40 weeks in CheckMate-017 and to eight months in CheckMate-057 with an exponential distribution thereafter.…”

“…Comparison SPMs include 1) nonvalidated SPMs selected based on AIC, assessment of proportional hazards, and visual inspection only; 2) HTA body models (ERG SPM) that were proposed by the NICE Evidence Review Group (ERG) 15 ; and 3) validated SPM models selected by Bristol Myers Squibb (BMS) after comparisons with other trial data and external data sources. [14][15][16][17][18] In this previous work, dependent and independent parametric models were considered by BMS in model selection, although the focus of this article is restricted to the nivolumab arm. Validated SPMs were those used in costeffectiveness models submitted to NICE and other HTA bodies and later published in peer-reviewed journals and were selected conservatively to avoid criticism by the ERG and other HTA reviewers.…”