Cost Effectiveness of Treatment Sequences in Advanced Renal Cell Carcinoma - Beyond the Abstract

In recent years, several new first-line treatment options for metastatic renal cell carcinoma (mRCC) have been approved by the Food & Drug Administration (FDA), including five novel immunotherapy-based combinations.1-5 These first-line options are included in current National Comprehensive Cancer Network (NCCN) and European Association of Urology (EAU) guidelines based on the patient’s International Metastatic RCC Database Consortium (IMDC) risk category.6,7

Intermediate/poor-risk patients can select between nivolumab plus ipilimumab (nivo/ipi) or cabozantinib alone if patients are at risk of immune toxicity.2,4,6,8 Meanwhile, patients in any IMDC risk category can select pembrolizumab plus axitinib (pembro/axi), pembro plus lenvatinib (pembro/len), or nivolumab plus cabo (nivo/cabo).1,2,5,6 Taking subsequent second-line options into consideration such as lenvatinib plus everolimus (len/evero) or cabo, several possible treatment sequences exist for the first- and second-line treatment of mRCC. However, absent head-to-head comparisons via randomized controlled trials (RCTs) between treatment sequences, clinicians must recommend treatment to patients based on their experience and the best available clinical data. In light of rising healthcare costs, clinicians and payers must consider all factors including the cost effectiveness of treatment sequences.

To help guide informed decision-making, we performed the first cost-effectiveness (CE) analysis of the five first-line regimens and subsequent second-line regimens for the treatment of mRCC. We developed a comprehensive Markov model to study CE from a US payer perspective for the following treatment sequences: 1) nivo/cabo followed by len/evero, 2) nivo/ipi followed by cabo, 3) pembro/axi followed by cabo, and 4) pembro/len followed by cabo. The patient cohorts were modeled using the characteristics of patients enrolled in CheckMate-2144, KEYNOTE-4265, CLEAR1, CheckMate-9ER2, METEOR9, and NCT0113673310. Transitions between health states were based on transition probabilities calculated for PFS, OS, and discontinuation rates from the phase 3 trials of the respective treatments. The appropriate second-line therapy following doublet immunotherapy was based on data from CheckMate-214 and KEYNOTE-426, while the second-line therapy following pembro/len or nivo/cabo was a treatment not used first-line. Furthermore, to account for the effects of different clinical and utility parameters, we performed a probabilistic sensitivity analysis (PAS) via Monte Carbo simulation of 10,000 iterations. The primary outputs of the models included total costs, life years (LYs), quality-adjusted LYs (QALYs), and incremental CE ratios (ICERs). The analyses were conducted at a five- and ten-year time horizon.

Using a threshold of $150,000 per QALY to identify a treatment approach as “cost-effective,” our results reveal that pembro/len followed by cabo, and pembro/axi followed by cabo are the more cost-effective treatment choices for patients with favorable-risk disease. Of these two options, the more cost-effective option will likely depend on the specific cost of len/axi. In fact, drug cost was the most significant factor identified by the one-way sensitivity model. For patients with intermediate/poor-risk disease, our results show that nivo/ipi followed by cabo is the most cost-effective regimen. In fact, all other treatment regimens were dominated in both the base analysis and sensitivity analysis, and nivo/ipi followed by cabo was the most cost-effective regimen in 96.2% of the 10,000 Monte Carlo simulations performed.

Overall, these findings underscore the value of these different treatment regimens based on cost-effectiveness, considering the impact that parameters including survival and adverse events have on the cost of treatment regimens. Importantly, our study also accounted for treatment pauses and discontinuation due to side effects with realistic timelines for restarting therapy in those cases. The results of our study can be used by clinicians to help determine the most appropriate treatment regimens for the treatment of mRCC.

Written by: Vidhu B. Joshi, MS1 Neil T. Mason, MBA2 & Jad Chahoud, MD, MPH3

  1. Villanova University Charles Widger School of Law, Villanova, PA USA
  2. Department of Individualized Cancer Medicine, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA
  3. Department of Genitourinary Oncology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA

References:

  1. Motzer, R. et al. Lenvatinib plus Pembrolizumab or Everolimus for Advanced Renal Cell Carcinoma. N Engl J Med 384, 1289-1300, doi:10.1056/NEJMoa2035716 (2021).
  2. Choueiri, T. K. et al. Nivolumab plus Cabozantinib versus Sunitinib for Advanced Renal-Cell Carcinoma. New England Journal of Medicine 384, 829-841, doi:10.1056/NEJMoa2026982 (2021).
  3. Motzer, R. J. et al. Avelumab plus Axitinib versus Sunitinib for Advanced Renal-Cell Carcinoma. New England Journal of Medicine 380, 1103-1115, doi:10.1056/NEJMoa1816047 (2019).
  4. Albiges, L. et al. Nivolumab plus ipilimumab versus sunitinib for first-line treatment of advanced renal cell carcinoma: extended 4-year follow-up of the phase III CheckMate 214 trial. ESMO open 5, e001079, doi:10.1136/esmoopen-2020-001079 (2020).
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  6. Network, N. C. C. NCCN Clinical Practice Guidelines in Oncology: Kidney Cancer. (2022).
  7. Ljungberg, B. et al. European Association of Urology Guidelines on Renal Cell Carcinoma: The 2022 Update. European urology, doi:10.1016/j.eururo.2022.03.006 (2022).
  8. Choueiri, T. K. et al. Cabozantinib Versus Sunitinib As Initial Targeted Therapy for Patients With Metastatic Renal Cell Carcinoma of Poor or Intermediate Risk: The Alliance A031203 CABOSUN Trial. Journal of Clinical Oncology 35, 591-597, doi:10.1200/jco.2016.70.7398 (2017).
  9. Choueiri, T. K. et al. Cabozantinib versus everolimus in advanced renal cell carcinoma (METEOR): final results from a randomised, open-label, phase 3 trial. The Lancet. Oncology 17, 917-927, doi:10.1016/S1470-2045(16)30107-3 (2016).
  10. Motzer, R. J. et al. Lenvatinib, everolimus, and the combination in patients with metastatic renal cell carcinoma: a randomised, phase 2, open-label, multicentre trial. The Lancet. Oncology 16, 1473-1482, doi:10.1016/s1470-2045(15)00290-9 (2015).
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