A Cost-effectiveness Analysis Comparing Pembrolizumab-Axitinib, Nivolumab-Ipilimumab, and Sunitinib for Treatment of Advanced Renal Cell Carcinoma.

OBJECTIVES: The US Food and Drug Administration (FDA) approved nivolumab-ipilimumab and pembrolizumab-axitinib as first-line treatments for metastatic, clear-cell, renal cell carcinoma (mRCC) based on results from CheckMate 214 and KEYNOTE-426. Our objective was to compare the adjusted, lifetime cost-effectiveness between nivolumab-ipilimumab, pembrolizumab-axitinib, and sunitinib for patients with mRCC. MATERIALS AND METHODS: A 3-state Markov model was developed comparing nivolumab-ipilimumab and pembrolizumab-axitinib to each other and sunitinib, over a 20-year lifetime horizon from a US medical center perspective. The clinical outcomes of nivolumab-ipilimumab and pembrolizumab-axitinib were compared using matching-adjusted indirect comparison. Costs of drug treatment, adverse events, and utilities associated with different health states and adverse events were determined using national sources and published literature. Our outcome was incremental cost-effectiveness ratio (ICER) using quality-adjusted life years (QALY). One-way and probabilistic sensitivity analyses were conducted. RESULTS: Nivolumab-ipilimumab was the most cost-effective option in the base case analysis with an ICER of $34,190/QALY compared with sunitinib, while the pembrolizumab-axitinib ICER was dominated by nivolumab-ipilimumab and was not cost-effective (ICER=$12,630,828/QALY) compared with sunitinib. The mean total costs per patient for the nivolumab-ipilimumab and pembrolizumab-axitinib arms were $284,683 and $457,769, respectively, compared with sunitinib at $241,656. QALY was longer for nivolumab-ipilimumab (3.23 QALY) than for adjusted pembrolizumab-axitinib (1.99 QALY), which was longer than sunitinib's (1.98 QALY). These results were most sensitive to treatment cost in both groups, but plausible changes did not alter the conclusions. CONCLUSIONS: The base case scenario indicated that nivolumab-ipilimumab was the most cost-effective treatment option for mRCC compared with pembrolizumab-axitinib and sunitinib.

Evaluation of Insurance Coverage and Cancer Stage at Diagnosis Among Low-Income Adults With Renal Cell Carcinoma After Passage of the Patient Protection and Affordable Care Act.

Importance: The association of the Patient Protection and Affordable Care Act (ACA) with insurance status and cancer stage at diagnosis among patients with renal cell carcinoma (RCC) is unknown. Objective: To test the hypothesis that the ACA may be associated with increased access to care through expansion of insurance, which may vary based on income. Design, Setting, and Participants: This retrospective cohort analysis included patients diagnosed with RCC from January 1, 2010, to December 31, 2016, in the National Cancer Database. Data were analyzed from July 1 to December 31, 2020. The periods from 2010 to 2013 and from 2014 to 2016 were defined as pre- and post-ACA implementation, respectively. Patients were categorized as living in a Medicaid expansion state or not. Exposures: Implementation of the ACA. Main Outcomes and Measures: The absolute percentage change (APC) of insurance coverage was calculated before and after ACA implementation in expansion and nonexpansion states. Secondary outcomes included change in stage at diagnosis, difference in the rate of insurance change, and change in localized disease between expansion and nonexpansion states. Adjusted difference-in-difference modeling was performed. Results: The cohort included 78 099 patients (64.7% male and 35.3% female; mean [SD] age, 54.66 [6.46] years), of whom 21.2% had low, 46.2% had middle, and 32.6% had high incomes. After ACA implementation, expansion states had a lower proportion of uninsured patients (adjusted difference-in-difference, -1.14% [95% CI, -1.98% to -1.41%]; P = .005). This occurred to the greatest degree among low-income patients through the acquisition of Medicaid (APC, 11.0% [95% CI, 8.6%-13.3%]; P < .001). Implementation of the ACA was also associated with an increase in detection of stage I and II disease (APC, 4.0% [95% CI, 1.6%-6.3%]; P = .001) among low-income patients in expansion states. Conclusions and Relevance: Among patients with RCC, ACA implementation was associated with an increase in insurance coverage status in both expansion and nonexpansion states for all income groups, but to a greater degree in expansion states. The proportion of patients with localized disease increased among low-income patients in both states. These data suggest that ACA implementation is associated with earlier RCC detection among lower-income patients.

Real-world symptoms, disease burden, resource use and quality of life in US patients with advanced renal cell cancer.

Aim: To assess symptoms, healthcare resource utilization and health-related quality of life in advanced renal cell carcinoma (aRCC) clinical practice. Materials & methods: The USA point-in-time survey of physicians and patients was conducted between February and September 2019. Results: Data were available for 227 patients. Mean (standard deviation) number of symptoms was 3.4 (3.2); differences were observed across International Metastatic RCC Database Consortium risk categories (p < 0.001), with fewer symptoms in favorable-risk patients. Disease burden, measured by greater healthcare resource utilization and worse health-related quality of life, was high, particularly in International Metastatic RCC Database Consortium intermediate- or poor- versus favorable-risk patients. In total, 45 patients (21.6%) were hospitalized due to aRCC within a 6-month period, 35 (16.8%) had one hospitalization and ten (4.8%) experienced ≥2 hospitalizations due to aRCC. Mean (standard deviation) 19-Item Functional Assessment of Cancer Therapy Kidney Symptom Index score was 53.6 (13.2) for this population, significantly lower than the reference value (59.8; p < 0.001). Conclusion: A clear need exists for improved disease management in patients with aRCC.

Lay abstract Late-stage/advanced renal cell carcinoma (aRCC) is kidney cancer that has spread to other body parts. aRCC is expensive to treat and affects patients in many ways. New treatments have become available, including tyrosine kinase inhibitors and immuno-oncology therapies. The type of treatment recommended depends on the patient's International Metastatic RCC Database Consortium risk score. This is a way of classifying patients as having a good, intermediate or poor survival risk. We asked physicians questions about their patients such as their age, how long they had aRCC, their treatment and symptoms, and asked patients how aRCC affected their lives, including how often they visited doctors and hospitals. aRCC had the greatest effect on patients with poor-risk scores. Those patients had more symptoms and worse quality of life than patients with intermediate or good risk scores. Treatment also affected patients' lives, although not as much as risk score. Patients with aRCC need better treatment options to help improve their quality of life.

COVID-19 and financial toxicity in patients with renal cell carcinoma.

PURPOSE: To ascertain renal cell carcinoma (RCC) financial toxicity on COVID-19 during the COVID-19 crisis as patients are struggling with therapeutic and financial implications. METHODS: An online survey was conducted from March 22 to March 25, 2020. It included baseline demographic, clinicopathologic, treatment-related information, anxiety levels related to COVID-19, questions related to financial concerns about COVID-19 as well as the validated 11-item COST measure. RESULTS: Five-hundred-and-thirty-nine patients (39%:58% male:female) from 14 countries responded. 23% of the patients did not feel in control of their financial situation but 8% reported being very satisfied with their finances. The median COST score was 21.5 (range 1-44). Metastatic patients who have not started systemic therapy had a COST score (19.8 range 2-41) versus patients on oral systemic therapy had a COST score (23.9 range 4-44). Patients in follow-up after surgery had a median COST score at 20.8 (range 1-40). A low COST scores correlated (p < 0.001) were female gender (r = 0.108), younger age (r = 0.210), urban living situation (r = 0.68), a lower educational level (r = 0.155), lower income (r = 0.165), higher anxiety about acquiring COVID-19 (r = 0.198), having metastatic disease (r = 0.073) and a higher distress score about cancer progression (r = 0.224). CONCLUSION: Our data highlight severe financial impact of COVID-19. Acknowledging financial hardship and thorough counseling of cancer patients should be part of the conversation during the pandemic. Treatment and surveillance of RCC patients might have to be adjusted to contemplate financial and medical needs.

Cost-effectiveness of Pembrolizumab Plus Axitinib Vs Nivolumab Plus Ipilimumab as First-Line Treatment of Advanced Renal Cell Carcinoma in the US.

Importance: Checkpoint 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. Objective: To evaluate the cost-effectiveness of pembrolizumab-axitinib and nivolumab- ipilimumab in the first-line treatment of advanced renal cell carcinoma. Design, Setting, and Participants: For 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 Measures: An 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). Results: Pembrolizumab-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 Relevance: The 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.

Cost-effectiveness of pembrolizumab plus axitinib as first-line therapy for advanced renal cell carcinoma.

Aim: To evaluate the cost-effectiveness of first-line treatments for advanced renal cell carcinoma with pembrolizumab plus axitinib compared with sunitinib from the US payer perspective. Patients & methods: A Markov model was developed for this purpose. The clinical data were obtained from the KEYNOTE-426 trial. Utility values and direct costs related to the treatments were gathered from the published studies. Results: The incremental cost-effectiveness ratios of pembrolizumab plus axitinib versus sunitinib was $249,704 per quality-adjusted life year, which was higher than a willingness-to-pay threshold of $150,000 per quality-adjusted life year. Conclusion: Pembrolizumab plus axitinib was not considered to be cost-effective versus sunitinib as a first-line treatment for patients with advanced renal cell carcinoma from the US payer perspective.

Medicaid Expansion Did not Improve Time to Treatment for Young Patients With Metastatic Renal Cell Carcinoma.

INTRODUCTION: The absence of health insurance coverage has been associated with worse outcomes for patients with metastatic renal cell carcinoma (mRCC). Medicaid expansion in the United States was an important provision of the Affordable Care Act, which increased the number of low-income individuals eligible for Medicaid starting in January 2014 in several states. The effect of Medicaid expansion on access to healthcare for patients with mRCC is unknown. MATERIALS AND METHODS: We performed a retrospective cohort study of 6844 patients aged < 65 years with mRCC at diagnosis within the National Cancer Database. We compared the time to treatment and the rates of no insurance before (2012-2013) and after (2015-2016) expansion between patients living in states that had and had not expanded Medicaid using difference-in-difference (DID) analyses. DIDs were calculated using linear regression analysis with adjustment for sociodemographic covariates. RESULTS: The rate of no insurance did not change in the expansion states compared with the nonexpansion states (DID, -0.55%; 95% confidence interval, -3.32% to 2.21%; P = .7). The percentage of patients receiving treatment within 60 days of diagnosis had increased in the expansion states from 43% to 49% and in the nonexpansion states from 42% to 46% after expansion. No change was found in treatment within 60 days of diagnosis among all patients (DID, 2.81%; 95% confidence interval, -2.61% to 8.22%; P = .3). CONCLUSIONS: Medicaid expansion was not associated with improved healthcare access for patients with mRCC as reflected by timely treatment. Future work should assess the association between Medicaid expansion and oncologic outcomes.

Clinical and economic outcomes of treatment sequences for intermediate- to poor-risk advanced renal cell carcinoma.

Aim: To assess the cost-effectiveness of treatment sequences for patients with intermediate- to poor-risk advanced renal cell carcinoma. Patients & methods: A discrete event simulation model was developed to estimate patients' lifetime costs and survival. Efficacy inputs were derived from the CheckMate 214 and CheckMate 025 studies and network meta-analyses. Safety and cost data were obtained from the published literature. Results: The estimated average quality-adjusted life-years (QALYs) gained was the highest on nivolumab + ipilimumab-initiated sequences (3.6-5.3 QALYs) versus tyrosine kinase inhibitor (TKI)-initiated sequences (2.1-3.7 QALYs). Incremental cost per QALY gained for nivolumab + ipilimumab-initiated sequences was below the willingness-to-pay threshold of $150,000 versus other sequences. Conclusion: Immuno-oncology combination therapy followed by TKIs is cost-effective versus TKI sequences followed by immuno-oncology or sequencing TKIs.

Is there a clinical role for frozen section analysis during partial nephrectomy? A multicenter experience over 10 years.

BACKGROUND: Frozen section analysis (FSA) is frequently performed during partial nephrectomy (PN). We investigate the utility of intraoperative FSA by evaluating its impact on final surgical margin (SM) status. METHODS: Between January 1995 and December 2005, a series of patients who were treated with open PN for renal cell carcinoma was prospectively analyzed. During PN, each patient underwent a FSA on renal parenchyma distal margin. If FSA was positive for infiltration a deeper excision was performed till obtaining a negative FSA. SM outcome of the FSA was compared with the final pathology report. Recurrence-free survival (RFS) and cost analysis on the FSA performed were analyzed. RESULTS: A total number of 373 patients were enrolled. FSA was performed in all the patients considered for PN. Fifteen patients had a conversion to radical nephrectomy. Positive SMs at the definitive pathological outcome were found in 36 patients (9.6%). FSA was positive in eight patients (2.1%). In that eight cases after a deeper excision the definitive pathological outcome on SM was still positive in two cases. FSA revealed just 14.3% of the positive SM. Patients with positive SM had a worse follow up considering RFS (P<0.05). Kaplan-Meier analysis revealed that FSA did not considerably contribute to prevent recurrence (P=0.35). 1438 euros was the mean cost of performing a FSA during PN. CONCLUSIONS: FSA during PN does not reduce the risk of positive SMs. The use of FSA has also a higher cost related to the procedure.

Evaluating Partitioned Survival and Markov Decision-Analytic Modeling Approaches for Use in Cost-Effectiveness Analysis: Estimating and Comparing Survival Outcomes.

OBJECTIVE: The objective of this study was to assess long-term survival outcomes for nivolumab and everolimus in renal cell carcinoma predicted by three model structures, a partitioned survival model (PSM) and two variations of a semi-Markov model (SMM), for use in cost-effectiveness analyses. METHODS: Three economic model structures were developed and populated using parametric curves fitted to patient-level data from the CheckMate 025 trial. Models consisted of three health states: progression-free, progressed disease, and death. The PSM estimated state occupancy using an area under-the-curve approach from overall survival (OS) and progression-free survival (PFS) curves. The SMMs derived transition probabilities to calculate patient flow between health states. One SMM assumed that post-progression survival (PPS) was independent of PFS duration (PPS Markov); the second SMM assumed differences in PPS based on PFS duration (PPS-PFS Markov). RESULTS: All models provide a reasonable fit to the observed OS data at 2 years. For estimating cost effectiveness, however, a more relevant comparison is between estimates of OS over the modeling horizon, because this will likely impact differences in costs and quality-adjusted life-years. Estimates of the incremental mean survival benefit of nivolumab versus everolimus over 20 years were 6.6 months (PSM), 7.6 months (PPS Markov), and 7.4 months (PPS-PFS Markov), reflecting non-trivial differences of + 14% and + 11%, respectively, compared with PSM. CONCLUSIONS: The evidence from this study and previous work highlights the importance of the assumptions underlying any model structure, and the need to validate assumptions regarding survival and the application of treatment effects against what is known about the characteristics of the disease.

Sunitinib First-line Treatment in Metastatic Renal Cell Carcinoma: Costs and Effects.

BACKGROUND/AIM: Tyrosine kinase inhibitors are important in the treatment of metastatic renal cell cancer (mRCC). The aim of the study was to evaluate the costs and effects of sunitinib in mRCC. PATIENTS AND METHODS: A total of 81 mRCC patients who received first-line sunitinib therapy between 2010 and 2014 were recruited. Drug doses, laboratory and imaging studies, outpatient visits and inpatient stays were recorded. Health-related quality of life (HRQoL) was measured (15D- and EQ-5D - 3L questionnaires). RESULTS: The cost of sunitinib (mean 22,268 €/patient range 274 € to 105,121 €) covered 73% of the total costs during the treatment period. The total treatment cost was 30,530 €/patient (range=1,661-111,516 €). The median overall survival was 17.9 months. HRQoL decreased during treatment. CONCLUSION: The main cost during sunitinib treatment of mRCC was the drug itself (73% of the total costs). Drug costs and HRQoL should be considered when choosing treatment for mRCC.

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

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Rising Economic Burden of Renal Cell Carcinoma among Elderly Patients in the USA: Part II-An Updated Analysis of SEER-Medicare Data.

BACKGROUND: The influx of new oncologic technologies has changed the treatment landscape of renal cell carcincoma (RCC) in the last decade. This study updated a previously published paper on the economic burden of RCC in the USA by using more recent data to examine the impact of various forms of new oncologic technologies on the economic burden of RCC. METHODS: Using the linked Surveillance, Epidemiology, and End Results (SEER)-Medicare database, we employed prevalence and incidence costing approaches to estimate RCC costs from the payer's perspective. We conducted a longitudinal analysis of cost data per patient per month for a prevalence cohort of patients with RCC to determine which category of new technology (surgery, radiation, or cancer drugs) was the major cost driver for RCC. We then applied the incidence costing approach to estimate costs related to RCC by care phase (initial, continuing, and terminal) and compared costs between two incidence cohorts to examine how new technology affected the economic burden of RCC over time. RESULTS: After controlling for demographic factors, clinical characteristics, neighborhood socioeconomic status, and time trend, we found that rising per patient per month costs were driven by new technologies in cancer drugs. Incidence-based analysis showed the annual net cost (2018 US$) for patients with distant-stage RCC diagnosed between 2002 and 2006 was $51,639, $19,025, $76,603, and $29,045 for the initial, continuing (year 1), terminal (died from RCC), and terminal (died from other causes) care phases, respectively. Costs increased to $70,703, $34,716, $107,989, and $47,538, respectively, for the incidence cohort diagnosed between 2007 and 2011. CONCLUSION: The rising economic burden of RCC was most pronounced among patients with distant-stage RCC, and driven primarily by new cancer drugs.

Cost-effectiveness Analysis of Pembrolizumab Plus Axitinib Versus Sunitinib in First-line Advanced Renal Cell Carcinoma in China.

BACKGROUND AND OBJECTIVES: In first-line treatment of advanced renal cell carcinoma (aRCC), the KEYNOTE-426 study demonstrated a significant progression-free survival and overall survival for pembrolizumab plus axitinib in comparison with sunitinib. The objective of the current study was to evaluate the cost effectiveness of pembrolizumab plus axitinib versus sunitinib for previously untreated patients with aRCC in China. METHODS: A Markov model was used to estimate the costs and health outcomes of treatment of aRCC with sunitinib or pembrolizumab plus axitinib. Univariable and probabilistic sensitivity analyses were performed to determine the robustness of the model outcomes. Additional subgroup analyses were also performed. The primary outputs of the model included the total cost, life-years (LYs), quality-adjusted LYs (QALYs), and incremental cost-effectiveness ratio (ICER). RESULTS: Pembrolizumab plus axitinib provided an additional 2.461 LYs (1.650 QALYs). The total cost per patient was US$178,725 for pembrolizumab plus axitinib and US$87,693 for sunitinib. The ICER for pembrolizumab plus axitinib was US$55,185/QALY versus sunitinib. Sensitivity analyses found the results to be most sensitive to pembrolizumab cost and overall hazard ratio. The results of subgroup analyses showed that the ICER remained greater than US$32,000/QALY across the all patient subgroups. CONCLUSIONS: Pembrolizumab plus axitinib is not likely to be cost effective versus sunitinib for patients with previously untreated aRCC at a threshold value of US$29,306/QALY.

Metastatic Renal Cell Cancer: An Analysis of Reimbursement Decisions.

INTRODUCTION: Metastatic renal cell carcinoma is a complex cancer for which several drugs have been developed over the years. More recently, drugs that target the specific cancer cell mutations have been developed for metastatic cell carcinoma. However, even with the recent influx of targeted therapy options, significant unmet needs exist in around half of treated renal cell carcinoma patients following the failure of first-line therapy. The aim of this study was to review the health technology appraisals of renal cell carcinoma treatments in several countries to establish what factors might affect the reimbursement decisions. METHODS: The reimbursement data for 10 drugs in several countries were collated from the health technology assessment bodies for each country. The data included information on clinical trials used in the submission documents for the health technology assessment, the reimbursement decisions and the reasons for those decisions, as well as any specific restrictions for use of any of the included drugs. RESULTS: Of the 10 drugs reviewed, only everolimus received a positive reimbursement decision by all the health technology assessment bodies included in the study. The most common reason for a negative reimbursement decision was lack of demonstration of cost-effectiveness of the drugs. Another frequently cited reason was unproven clinical efficacy and poor impact on overall survival. CONCLUSION: Despite the many treatment guidelines and current treatment options that are available for renal cell carcinoma, there remains an unmet need in patients with metastatic renal cell carcinoma. On the basis of this analysis, the key reason for a drug not obtaining a positive reimbursement decision is due to poor efficacy or uncertainty of the drug's efficacy. FUNDING: Eisai, Inc.

Economic burden of renal cell carcinoma among older adults in the targeted therapy era.

OBJECTIVE: This study examined the economic burden of renal cell carcinoma (RCC) among older adults. The study also examined healthcare costs by types of resources used and stage at which RCC was diagnosed. METHODS: The study analyzed the Surveillance Epidemiology and End Result-Medicare linked data. We included a prevalent cohort of RCC patients from 2013, diagnosed and continuously enrolled in Medicare from 2005 to 2013. RCC patients were matched to controls selected from a 5% sample of noncancer beneficiaries using propensity score matching to calculate incremental costs. Total healthcare costs (THC) were calculated using a phase-based approach, which classified patients into early, continuing, and late phases of care. Costs were also examined by types of resources used and stage at which RCC was diagnosed. Generalized linear models estimated annual incremental costs per patient. The number of older RCC patients was calculated using SEER-Stat and ProjPrev software. The average incremental THC was multiplied by the estimated number of RCC patients to calculate the total economic burden of RCC among older adults. RESULTS: The study included 10,392 each of RCC and control patients. The average annual THC associated with RCC was $7,419 for all phases, $22,752 for the initial phase, $4,860 for the continuing phase, and $13,232 for the late phase of care. The average THC was $4,584 for patients diagnosed at stage I, $4,727 for stage II, $9,331 for stage III, and $31,637 for stage IV. For patients diagnosed at stages I to III, hospital cost (approximately $1,500-$3,400) was the largest component of THC. For stage IV patients, prescription drug cost ($11,747) was the largest component of THC. The projected number of older RCC patients in 2015 was 204,256. The annual economic burden of RCC after weighting for proportion of patients diagnosed at various stages was estimated to be $2.1 billion. CONCLUSIONS: RCC was associated with a significant economic burden on Medicare. Healthcare costs associated with RCC varied substantially between early stage and metastatic patients. This research provided a baseline that can be used to assess the economic value of emerging therapies among older RCC patients.

First-line Nivolumab Plus Ipilimumab vs Sunitinib for Metastatic Renal Cell Carcinoma: A Cost-effectiveness Analysis.

IMPORTANCE: Recently, new drugs have been approved for the first-line treatment of metastatic renal cell carcinoma (mRCC). Nivolumab plus ipilimumab significantly increases overall survival for intermediate- and poor-risk patients with mRCC. However, considering the high cost of nivolumab plus ipilimumab, there is a need to assess its value by considering both efficacy and cost. OBJECTIVE: To evaluate the cost-effectiveness of nivolumab plus ipilimumab vs sunitinib in the first-line setting for intermediate- and poor-risk patients with mRCC from the US payer perspective. DESIGN, SETTING, AND PARTICIPANTS: A Markov model was developed to compare the lifetime cost and effectiveness of nivolumab plus ipilimumab vs sunitinib in the first-line treatment of mRCC using outcomes data from the CheckMate 214 phase 3 randomized clinical trial, which included 1096 patients with mRCC (median age, 62 years) and compared nivolumab plus ipilimumab vs sunitinib as first-line treatment of mRCC. In the analysis, patients were modeled to receive sunitinib or nivolumab plus ipilimumab for 4 doses followed by nivolumab monotherapy. MAIN OUTCOMES AND MEASURES: Life-years, quality-adjusted life-years (QALYs), and lifetime costs were estimated, at a willingness-to-pay threshold of $100 000 to $150 000 per QALY. Univariable, 2-way, and probabilistic sensitivity analyses were performed to evaluate the model uncertainty. Additional subgroup analyses were performed. RESULTS: Nivolumab plus ipilimumab provided an additional 0.96 QALYs, at a cost of $108 363 per QALY. Sensitivity analyses found the results to be most sensitive to overall survival hazard ratio (0.63; 95% CI, 0.44-0.89) and mean patient weight (70 kg, range, 40-200 kg). Other variables, such as the cost of nivolumab plus ipilimumab (mean, $32 213.44; range, $25 770.75-$38 656.13), utility values for nivolumab plus ipilimumab (mean, 0.82; range, 0.65-0.98), and proportion receiving nivolumab in sunitinib arm (mean, 0.27; range, 0.22-0.32), had a moderate or minor influence on model results. Subgroup analyses demonstrated that nivolumab plus ipilimumab was most cost-effective for patients with programmed cell death 1 ligand 1 expression of at least 1% ($86 390 per QALY). CONCLUSIONS AND RELEVANCE: In this model, nivolumab plus ipilimumab was estimated to be cost-effective compared with sunitinib for intermediate- and poor-risk patients with mRCC at a willingness-to-pay threshold from $100 000 to $150 000 per QALY.

Economic evaluation of sunitinib versus pazopanib and best supportive care for the treatment of metastatic renal cell carcinoma in Chile: cost-effectiveness analysis and a mixed treatment comparison.

Background: Sunitinib and Pazopanib are two metastatic renal cell carcinoma (MRCC) treatment alternatives, however the health system in Chile does not consider coverage for any. The cost-effectiveness versus relevant comparator was assessed to support evidence-based decision making. Methods: A four health states Markov model was built: first, second line treatments, BSC and death. Benefits were measured in QALYs, and efficacy estimates were obtained from an indirect treatment comparison. A 10-year time horizon and a 3% undifferentiated discount rate were considered. Deterministic and probabilistic sensitivity analyses were performed. Results: The costs of treating MRCC with Sunitinib were higher than Pazopanib and BSC. When comparing Sunitinib versus Pazopanib, the incremental benefit is small favoring Sunitinib (0.03 QALYs). The base case scenario shows an average ICER of PA versus BSC of US$62,327.11/QALY and of US$85,885/QALY for Sunitinib versus Pazopanib. The ICER was most sensitive to the OS relative to BSC, where evidence was associated to important bias. Conclusions: Sunitinib or Pazopanib can be considered cost-effective if a 3 GDP per-capita threshold is assumed. The decision between SU or PA is highly sensitive to the price of the drugs, rather than the outcomes. Therefore, the decision might be made based on cost-minimization exercise.

Economic Burden of Metastatic Clear-Cell Renal Cell Carcinoma for French Patients Treated With Targeted Therapies.

BACKGROUND: Targeted therapies have transformed the treatment of metastatic clear-cell renal cell carcinoma (mccRCC). Despite the importance of mccRCC, studies on its economic burden in daily practice are sparse. The purpose of this retrospective study was to evaluate cost of illness for 224 patients with mccRCC included in the cohort published by Thiery-Vuillemin et al (Factors influencing overall survival for patients with metastatic clear-cell renal cell-carcinoma in daily practice. Clin Genitourin Cancer 2018; 16:e297-305), and then to determine the explanatory factors of cost of illness. PATIENTS AND METHODS: The study was performed from the French Public Healthcare System perspective with lifetime horizon. Only direct medical costs were included. Multiple linear regression was used to search for explanatory factors of cost of illness. The robustness of results was assessed. RESULTS: The mean cost of illness was estimated at €71,185 ± 52,683. Outpatient/inpatient treatment and hospitalization represented 76.0% and 19.7% of this cost, respectively. After adjustment, 5 explanatory factors were identified: time of disease control for the metastatic first-line treatment ≥6 months, number of lines of treatment >2, nephrectomy at metastatic stage, lack of metastases at presentation, and age at metastatic diagnosis younger than 65 years. Individually, they increased cost of illness by 128%, 95%, 53%, 53%, and 23%, respectively. CONCLUSION: Although it is difficult to transpose our economic evaluation results to those obtained in other countries, it should be noted that our findings were consistent with them and robust. To our knowledge, our study was the first to accurately identify explanatory factors of cost of illness. Identifying them could enable us to predict the budgetary effect on a regional level of managing patients who began their first-line treatment with a targeted therapy.