Research Article: Treatment sequences for advanced renal cell carcinoma: A health economic assessment

Date Published: August 29, 2019

Publisher: Public Library of Science

Author(s): Baris Deniz, Apoorva Ambavane, Shuo Yang, Arman Altincatal, Justin Doan, Sumati Rao, M. Dror Michaelson, Sarah P. Psutka.


Advanced renal cell carcinoma (RCC) is commonly treated with vascular endothelial growth factor or mammalian target of rapamycin inhibitors. As new therapies emerge, interest grows in gaining a deeper understanding of treatment sequences. Recently, we developed a patient-level, discretely integrated condition event (DICE) simulation to estimate survival and lifetime costs for various cancer therapies, using a US payer perspective. Using this model, we explored the impact of treatments such as nivolumab and cabozantinib, and compared the clinical outcomes and cost consequences of commonly used treatment algorithms for patients with advanced RCC.

Included treatment sequences were pazopanib or sunitinib as first-line treatment, followed by nivolumab, cabozantinib, axitinib, pazopanib or everolimus. Efficacy inputs were derived from the CheckMate 025 trial and a network meta-analysis based on available literature. Safety and cost data were obtained from publicly available sources or literature.

Based on our analysis, the average cost per life-year (LY) was lowest for sequences including nivolumab (sunitinib → nivolumab, $75,268/LY; pazopanib → nivolumab, $84,459/LY) versus axitinib, pazopanib, everolimus and cabozantinib as second-line treatments. Incremental costs per LY gained were $49,592, $73,927 and $30,534 for nivolumab versus axitinib, pazopanib and everolimus-containing sequences, respectively. The model suggests that nivolumab offers marginally higher life expectancy at a lower cost versus cabozantinib-including sequences.

Treatment sequences using nivolumab in the second-line setting are less costly compared with sequential use of targeted agents. In addition to efficacy and safety data, cost considerations may be taken into account when considering treatment algorithms for patients with advanced RCC.

Partial Text

Globally, kidney cancer is responsible for 2.4% of all adult malignancies, with approximately 338,000 new cases and 114,000 deaths annually [1]. Renal cell carcinoma (RCC) is the most common type of kidney cancer [2], with a poor prognosis: the 5-year relative survival rate is ~12% for metastatic RCC [3]. Historically, in the pre-targeted therapy era, median survival for people with metastatic RCC was ~8 months with no treatment [4] or ~13 months with immunotherapy [5].

Table 1 presents cost and clinical outcomes associated with treatment sequences for advanced RCC. The analysis suggests that sequences including nivolumab as second-line treatment were associated with marginally higher life-years (LYs) (4.21 vs. 3.99 years), shorter treatment duration (0.65 vs. 0.72 years), and lower total lifetime costs (first-line sunitinib: $317,056 vs. $335,378; first-line pazopanib: $355,770 vs. $374,093) versus sequences with cabozantinib.

In this analysis, we assessed the cost and health outcomes associated with treatment sequences used for those patients who continue to progress on first-line treatment for advanced RCC. The treatment sequences included in the analysis are reflective of the current clinical practice, as determined based on NCCN guidelines [13]. Further, key prognostic indicators of health outcomes were assessed, including MSKCC risk score.

Using a patient-level DICE simulation, the study suggested that, of the treatment sequences evaluated, nivolumab-containing sequences were associated with lowest cost per LY gained. The model suggests that nivolumab-including sequences provide higher LYs gained compared with all other sequences studied. The incremental costs per LY gained for nivolumab is estimated to be well below the commonly used willingness-to-pay threshold in the United States, especially when compared against cabozantinib-including sequences where there is a cost savings.




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