Cost–effectiveness analysis of nivolumab plus cabozantinib versus sunitinib as first-line therapy in advanced renal cell carcinoma
Abstract
Aim: To evaluate the cost–effectiveness of first-line treatment for advanced renal cell carcinoma with nivolumab plus cabozantinib versus sunitinib from a US payer perspective. Methods: Economic outcomes were estimated with Markov and partitioned survival models. Efficacy, safety and other data were taken from the CheckMate 9ER trial. Costs and utilities were gathered from published sources. Sensitivity analyses addressed model uncertainties. Results: The incremental cost–effectiveness ratio of nivolumab plus cabozantinib versus sunitinib was US$555,663 and $531,748 per quality-adjusted life year in the Markov and partitioned survival models, respectively, exceeding the willingness-to-pay threshold (US$150,000 per quality-adjusted life-year). Sensitivity analyses showed robust outcomes. Conclusion: From a US payer perspective, first-line nivolumab plus cabozantinib for advanced renal cell carcinoma is not cost effective.
Plain language summary
Renal cell carcinoma (RCC) is a common cancer in the USA. Up to 30% of patients with RCC are in an advanced stage of disease at diagnosis. RCC is difficult to cure, with an 11% chance of survival after 5 years for patients with advanced RCC. A recent clinical study showed that nivolumab plus cabozantinib (NC) had a greater benefit in patients with advanced RCC than sunitinib. The US FDA approved NC for advanced RCC, but NC is relatively expensive. This study explored the cost–effectiveness of NC for advanced RCC versus sunitinib for a US payer using two cost–effectiveness models developed based on the results of the aforementioned clinical study. The results showed that to gain an additional year in perfect health, NC costs an average of US$555,663 or $531,748 more versus sunitinib, which is more than a US payer is willing to pay for an additional year in perfect health ($150,000). Therefore, NC for advanced RCC is not cost-effective versus sunitinib for a US payer at current prices.
Papers of special note have been highlighted as: • of interest; •• of considerable interest
References
- 1. Surveillance, Epidemiology and End Results Program. Cancer stat facts: kidney and renal pelvis cancer. https://seer.cancer.gov/statfacts/html/kidrp.html
- 2. . First-line nivolumab plus ipilimumab vs sunitinib for metastatic renal cell carcinoma: a cost–effectiveness analysis. JAMA Oncol. 5(4), 491–496 (2019). • Discusses a method for estimating the utility of nivolumab plus cabozantinib (NC) in the progression-free survival (PFS) state.
- 3. . Renal cancer. Lancet 387(10021), 894–906 (2016).
- 4. Nivolumab versus everolimus in advanced renal-cell carcinoma. N. Engl. J. Med. 373(19), 1803–1813 (2015).
- 5. Cabozantinib versus everolimus in advanced renal cell carcinoma (METEOR): final results from a randomised, open-label, phase 3 trial. Lancet Oncol. 17(7), 917–927 (2016).
- 6. Nivolumab plus cabozantinib versus sunitinib for advanced renal-cell carcinoma. N. Engl. J. Med. 384(9), 829–841 (2021). •• Discusses the CheckMate 9ER trial, which is the key data source of this evaluation.
- 7. A randomized phase II study of cabozantinib and nivolumab versus nivolumab in recurrent endometrial cancer. J. Clin. Oncol. 38(15), 6010 (2020).
- 8. US FDA. FDA approves pembrolizumab plus axitinib for advanced renal cell carcinoma (2021). www.fda.gov/drugs/drug-approvals-and-databases/fda-approves-nivolumab-plus-cabozantinib-advanced-renal-cell-carcinoma
- 9. National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: kidney cancer version 4 (2021). www.nccn.org/professionals/physiciangls/pdf/kidney.pdf • Latest information on recommended regimens in the National Comprehensive Cancer Network guidelines.
- 10. Centers for Medicare and Medicaid Services. ASP drug pricing files (2021). www.cms.gov/Medicare/Medicare-Fee-for-Service-Part-B-Drugs/McrPartBDrugAvgSalesPrice/2021ASPFiles.html
- 11. . The additional costs per month of progression-free survival and overall survival: an economic model comparing everolimus with cabozantinib, nivolumab, and axitinib for second-line treatment of metastatic renal cell carcinoma. J. Manag. Care Spec. Pharm. 24(4), 335–343 (2018).
- 12. . Cost-utility analysis of dapagliflozin versus saxagliptin treatment as monotherapy or combination therapy as add-on to metformin for treating type 2 diabetes mellitus. Appl. Health Econ. Health Policy 19(1), 69–79 (2021).
- 13. . Will the Markov model and partitioned survival model lead to different results? A review of recent economic evidence of cancer treatments. Expert Rev. Pharmacoecon. Outcomes Res. 21(3), 373–380 (2021).
- 14. US FDA. FDA approved drug products: labels for INLYTA (axitinib) tablets. www.accessdata.fda.gov/drugsatfda_docs/label/2012/202324lbl.pdf
- 15. US FDA. FDA approved drug products: labels for OPDIVO (nivolumab). www.accessdata.fda.gov/drugsatfdadocs/label/2019/125554s070lbl.pdf
- 16. US FDA. FDA approved drug products: labels for CABOMETYX (cabozantinib) tablets. www.accessdata.fda.gov/drugsatfdadocs/label/2019/208692s003lbl.pdf
- 17. . Survival modeling for the estimation of transition probabilities in model-based economic evaluations in the absence of individual patient data: a tutorial. Pharmacoeconomics 32(2), 101–108 (2014).
- 18. . Enhanced secondary analysis of survival data: reconstructing the data from published Kaplan–Meier survival curves. BMC Med. Res. Methodol. 12(1), 9 (2012). •• Discusses a method for reconstructing pseudoindividual patient data.
- 19. . Survival analysis for economic evaluations alongside clinical trials – extrapolation with patient-level data: inconsistencies, limitations, and a practical guide. Med. Decis. Making 33(6), 743–754 (2013). •• Discusses a method for survival model selection.
- 20. . United States life tables, 2018. Natl Vital Stat. Rep. 69(12), 1–45 (2020).
- 21. . First-line treatments for advanced renal-cell carcinoma with immune checkpoint inhibitors: systematic review, network meta-analysis and cost–effectiveness analysis. Ther. Adv. Med. Oncol. 12, 1758835920950199 (2020).
- 22. . License for use of current procedural terminology, fourth edition (“CPT®”). www.cms.gov/medicare/physician-fee-schedule/search?Y=0&T=0&HT=0&CT=3&H1=96413&M=5
- 23. US Bureau of Labor Statistics. The Consumer Price Index. data.bls.gov/cgi-bin/cpicalc.pl
- 24. Health-related quality of life and its determinants in patients with metastatic renal cell carcinoma. Qual. Life Res. 27(1), 115–124 (2018).
- 25. Cost–effectiveness of pembrolizumab plus axitinib as first-line therapy for advanced renal cell carcinoma. Immunotherapy 12(17), 1237–1246 (2020).
- 26. . Updating cost–effectiveness – the curious resilience of the $50,000-per-QALY threshold. N. Engl. J. Med. 371(9), 796–797 (2014).
- 27. . Model parameter estimation and uncertainty analysis: a report of the ISPOR-SMDM Modeling Good Research Practices Task Force Working Group-6. Med. Decis. Making 32(5), 722–732 (2012).
- 28. Cost–effectiveness of temsirolimus for first line treatment of advanced renal cell carcinoma. Value Health 13(1), 61–68 (2010).
- 29. . Cost–effectiveness of pembrolizumab as a second-line therapy for hepatocellular carcinoma. JAMA Netw. Open 4(1), e2033761 (2021).
- 30. . Modelled economic evaluation of nivolumab for the treatment of second-line advanced or metastatic squamous non-small-cell lung cancer in Australia using both partition survival and markov models. Appl. Health Econ. Health Policy 17(3), 371–380 (2019).
- 31. . Discounting in economic evaluations. Pharmacoeconomics 36(7), 745–758 (2018).
- 32. Pembrolizumab plus axitinib versus sunitinib for advanced renal-cell carcinoma. N. Engl. J. Med. 380(12), 1116–1127 (2019). • Study similar to CheckMate 9ER trial but conducted for pembrolizumab plus axitinib.
- 33. Cost–effectiveness of pembrolizumab plus axitinib versus sunitinib as first-line therapy in advanced renal cell carcinoma in the U.S. Oncologist 26(2), e290–e297 (2021).