Dataset Information

Cost-Effectiveness of Frontline Treatment for Advanced Renal Cell Carcinoma in the Era of Immunotherapies.

ABSTRACT: Background: Recent randomized controlled trials have demonstrated that immune checkpoint inhibitors (ICIs) improve patient outcomes, but whether these novel agents are cost-effective for untreated advanced renal cell carcinoma (aRCC) remains unclear. Materials and Methods: A microsimulation model was created to project the healthcare costs and outcomes of six strategies (lenvatinib-plus-pembrolizumab, nivolumab-plus-cabozantinib, nivolumab-plus-ipilimumab, pembrolizumab-plus-axitinib, avelumab-plus-axitinib, and sunitinib monotherapy) for patients with aRCC. Transition probability of patients was estimated from CLEAR, CheckMate 9ER, CheckMate 214, KEYNOTE-426, JAVELIN Renal 101, and other data sets by using parametric survival modeling. Lifetime direct medical costs, life years (LYs), quality-adjusted LYs (QALYs), and incremental cost-effectiveness ratios (ICERs) were estimated from a United States payer perspective. One-way and probabilistic sensitivity analyses were performed, along with multiple scenario analyses, to evaluate model uncertainty. Results: Of the six competing strategies, nivolumab-plus-cabozantinib yielded the most significant health outcomes, and the sunitinib strategy was the least expensive option. The cost-effective frontier consisted of the nivolumab-plus-cabozantinib, pembrolizumab-plus-axitinib, and sunitinib strategies, which displayed the ordered ICERs of $81282/QALY for pembrolizumab-plus-axitinib vs sunitinib and $453391/QALY for nivolumab-plus-cabozantinib vs pembrolizumab-plus-axitinib. The rest of the strategies, such as lenvatinib-plus-pembrolizumab, nivolumab-plus-ipilimumab, and avelumab-plus-axitinib, were dominated. The cost of sunitinib drove the model most influentially. Conclusions: For aRCC, the pembrolizumab-plus-axitinib strategy is likely to be the most cost-effective alternative at the willingness-to-pay threshold of $100,000.

SUBMITTER: Li S

PROVIDER: S-EPMC8458866 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:ImportanceThe effectiveness of immune checkpoint inhibitors (ICIs) and BRAF and MEK inhibitors has improved advanced melanoma recovery. However, it is unknown whether these novel therapies are cost-effective for newly diagnosed advanced melanoma with unknown BRAF status.ObjectiveTo compare the cost-utility of these novel agents and their combinations with or without BRAF gene testing guidance for treating newly diagnosed advanced melanoma with unknown BRAF status.Design and settingA decision-analytic model was adopted to project the outcomes of 8 strategies containing different ICIs and BRAF and MEK inhibitors for newly diagnosed advanced melanoma with unknown BRAF pathogenic variant status. The key clinical data were derived from the CheckMate 067, KEYNOTE-006, COMBI-d, and COMBI-v trials, and the cost and health preference data were derived from the literature. Costs were estimated from the US payer perspective.Main outcomes and measuresCosts, quality-adjusted life-years (QALYs), incremental cost-utility ratio (ICUR), and incremental net health benefits were calculated. Subgroup, 1-way, and probabilistic sensitivity analyses were performed.ResultsOf the 8 competing strategies, nivolumab plus ipilimumab without patient selection based on BRAF pathogenic variant testing yielded the most significant health outcome, and the nivolumab strategy was the cheapest option. The nivolumab, pembrolizumab, and nivolumab plus ipilimumab strategies formed the cost-effective frontier, which showed the ordered ICURs were $8593 (SD, $592 995)/QALY for pembrolizumab vs nivolumab and $125 593 (SD, $5 751 223)/QALY for nivolumab plus ipilimumab vs pembrolizumab. Other strategies, including the BRAF testing-guided strategies (BRAF pathogenic variant testing followed by corresponding regimens for BRAF wild and pathogenic variant tumors), were dominated or extended dominated. The most influential parameters were the treatment efficacy of these new regimens.Conclusions and relevanceFor newly diagnosed advanced melanoma with unknown BRAF pathogenic variant status, nivolumab plus ipilimumab and pembrolizumab strategies are likely to be the most cost-effective options. BRAF and MEK inhibitors might be productively placed in a second-line setting after BRAF pathogenic variant is confirmed.

Project description:ContextCurrent guidelines suggest several targeted therapies (TTs) and immunotherapies (ITs) in the treatment of advanced or metastatic renal cell carcinoma (mRCC). Ideal sequencing of these treatments is unclear.ObjectiveThe primary objective was to evaluate the overall survival (OS) data of the treatments approved for mRCC. Secondary objectives included evaluating other signs of efficacy and adverse events.Evidence acquisitionWe reviewed the current Food and Drug Administration-approved treatments for mRCC. Trials associated with approval were reviewed. We also included pre- and postapproval publications when appropriate.Evidence synthesisThere is minimal evidence supporting OS benefit for the nine approved TTs. They result in adverse events and are a considerable economic burden. For these reasons, their future role in mRCC treatment should be re-evaluated, given the emergence of IT that have demonstrated OS benefits. Accumulating long-term survival data with high-dose interleukin-2 treatment suggests that this older treatment could still be considered for eligible patients. Checkpoint inhibitors have shown promising OS and durable responses; as such, the high cost of treatment might be justified. However, the available evidence does not suggest that adding TT to IT would increase efficacy over IT alone, but would add toxicity.ConclusionsTrial data supporting OS benefit are much stronger for ITs than for TTs. Combining checkpoint inhibitors with TTs has not been shown to produce better OS than checkpoint inhibitors alone, while more adverse events are present. Granting drug approvals based on efficacy without demonstrated OS benefit should be revisited.Patient summaryApproved treatments for metastatic kidney cancer include targeted and immune-based therapies. The former commonly produces temporary tumour shrinkage, but survival benefits are unclear. All approved immunotherapies have increased survival, and a proportion of patients appear cured.

Project description:Background:We evaluated the cost-effectiveness of nivolumab versus everolimus in patients with advanced renal cell carcinoma (RCC) from a US payer perspective. Methods:A partitioned survival model consisting of three health states, progression-free survival (PFS), progressive disease, and death, was developed to evaluate the cost-effectiveness of intravenous nivolumab versus oral everolimus over a lifetime. The proportion of patients in each state was calculated based on parametric distributions fitted to PFS and overall survival (OS) data from CheckMate 025 (N = 821), a large randomized phase 3 trial of nivolumab versus everolimus for advanced RCC. Health state utility data were derived from CheckMate 025 EQ-5D data. Scenario analyses and deterministic and probabilistic sensitivity analyses assessed the impact of uncertainty in model inputs on outcomes. Results:Over a 25-year lifetime horizon, treatment with nivolumab resulted in a gain of 0.64 quality-adjusted life-years (QALYs) versus everolimus. Nivolumab had greater total costs versus everolimus ($US197,089 vs. $US163,902), mainly due to higher acquisition costs. The incremental cost-utility ratio (ICUR), a measure of incremental costs divided by incremental QALYs, was $US51,714 per QALY gained for nivolumab versus everolimus, and an incremental cost-effectiveness ratio was $US44,576 per life-year gained for nivolumab versus everolimus. In sensitivity analyses, average body weight had the greatest impact on the ICUR for nivolumab versus everolimus (base case $US51,714; range $US8863-$US94,566). At a $US150,000 willingness-to-pay (WTP) threshold, nivolumab had a 91.7% probability of being cost-effective versus everolimus. Conclusions:In the United States, at a WTP threshold of $US150,000 per QALY, nivolumab was found to be cost-effective. Key drivers of cost-effectiveness were survival inputs for OS and the average weight of patients; the latter directly affects nivolumab drug acquisition cost.

Project description:ImportanceCheckpoint inhibitor combination therapy represents a major advance in the first-line treatment of advanced renal cell carcinoma. Pembrolizumab-axitinib and nivolumab-ipilimumab have become standard of care options after demonstrating clinical efficacy against sunitinib in separate phase 3 trials. The cost-effectiveness of these regimens is unknown.ObjectiveTo evaluate the cost-effectiveness of pembrolizumab-axitinib and nivolumab- ipilimumab in the first-line treatment of advanced renal cell carcinoma.Design, setting, and participantsFor this economic evaluation, a primary microsimulation model was developed and run between August and December 2019. Separate analyses were conducted for an intermediate- and poor-risk patient population (base case) and a favorable-risk population (exploratory analysis) because prognosis is known to differ between risk groups; 100 000 patients with advanced renal cell carcinoma were simulated in each treatment arm. Survival, treatment regimens, and other relevant conditions were based on data from the phase 3 KEYNOTE-426 and CheckMate214 clinical trials. The study perspective was the US health care sector.Main outcomes and measuresAn incremental cost-effectiveness ratio was calculated for each of the 2 analyses and compared with a willingness-to-pay threshold of $100 000 per quality-adjusted life-year (QALY).ResultsPembrolizumab-axitinib was estimated to add 0.60 QALYs compared with nivolumab-ipilimumab in the base case analysis (3.66 vs 3.05 QALYs) and 0.25 QALYs compared with nivolumab-ipilimumab in the exploratory analysis (4.55 vs 4.30 QALYs), and was more costly (base case analysis: $562 927 vs $458 961; exploratory analysis: $589 035 vs $470 403). The incremental cost-effectiveness ratio was $172 532 per QALY in the base case analysis and $468 682 per QALY in the exploratory analysis. One-way sensitivity analyses revealed that the base case model was most sensitive to first-line drug prices (incremental cost-effectiveness ratio at upper limit of nivolumab price and lower limits of axitinib and pembrolizumab prices: $89 983, $102 287, and $114 943 per QALY, respectively). The exploratory analysis model was most sensitive to overall survival rates (incremental cost-effectiveness ratio at lower limit of pembrolizumab-axitinib rate and upper limit of nivolumab-ipilimumab rate: $278 644 and $285 684 per QALY, respectively).Conclusions and relevanceThe findings suggest that pembrolizumab-axitinib treatment is associated with greater QALYs compared with nivolumab/ipilimumab treatment in patients with advanced renal cell carcinoma but may not be cost-effective. Price reductions may make the cost of pembrolizumab-axitinib proportional to its clinical value and less financially burdensome to the US health care system.

Dataset Information

Cost-Effectiveness of Frontline Treatment for Advanced Renal Cell Carcinoma in the Era of Immunotherapies.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets