Table 3.

US-Based Cost-Effectiveness and Resource Utilization Studies with VEGF/VEGFr and mTOR Inhibitors

Study (drugs evaluated; sponsor)	Study design	Outcomes assessed	Findings	Implications
Gao et al28 (sorafenib; Bayer Pharmaceuticals)	Markov model to project the lifetime survival and cost associated with sorafenib + best supportive care vs best supportive care alone 3 disease states (per 3-month period): PFS, progression, death Resource utilization accounted for drugs, administrations, physician visits, monitoring, and AEs	FACT-G, FKSI Life-years gained	Lifetime per-patient costs (2004 US$): Sorafenib + best supportive care: $85,571 Best supportive care alone: $36,634 ICER: $75,354 per/life-year gained Key drivers of the model results were survival after progression and PFS probabilities for both treatment grounds	The ICER was within the established threshold that society is willing to pay ($50,000-$100,000 per life-year or per QALY). Therefore, sorafenib + best supportive care appears to be cost-effective in the management of advanced RCC
Moyneur et al29 (sorafenib, sunitinib; Bayer HealthCare)	Retrospective claims database analysis using MarketScan to evaluate the costs of second-line therapy with sorafenib or sunitinib in the treatment of patients with RCC Person-time approach was used in patients who had ≥1 switch in therapy from sunitinib to sorafenib or sorafenib to sunitinib	Incremental PMPM medical costs Outpatient costs Inpatient costs Pharmacy costs	Univariate PMPM total medical costs: $9159 (sunitinib > sorafenib) vs $7520 (sorafenib > sunitinib) Outpatient costs: $3400 vs $2148 (P <.001) Inpatient costs: $1755 vs $1582 Pharmacy costs: $4004 vs $3790	Compared with sunitinib, treatment with sorafenib initially resulted in statistically significantly lower costs in patients with RCC, primarily because of outpatient costs
Ozer-Stillman et al30 (axitinib, sorafenib; Bayer HealthCare)	Survival partition model to estimate direct lifetime medical costs and clinical outcomes for sunitinib-refractory patients starting second-line therapy Patients partitioned into 3 health states (PFS, postprogression survival, and death) using OS and PFS Kaplan-Meier curves from AXIS	Total costs Life-years gained QALYs gained	Total per-patient costs: $127,808 for sorafenib vs $159,800 for axitinib Life-years gained: 1.440 for sorafenib vs 1.423 for axitinib QALYs gained: 1.016 for sorafenib vs 1.015 for axitinib	Compared with axitinib, treatment with sorafenib after sunitinib failure is less expensive and provides a similar benefit in terms of life-years and QALYs
Casciano et al31 (everolimus, sorafenib; Novartis Pharmaceuticals)	Markov model to simulate cohort of patients with advanced RCC who failed therapy with sunitinib Cohorts modeled over 6-year time horizon in 8-week cycles from everolimus or sorafenib initiation Markov disease states included stable disease without AEs, stable disease with AEs, disease progression, and death	Cost per incremental life-year gained QALYs gained	Total average per-patient cost of treatment with everolimus vs sorafenib was $81,643, primarily because of acquisition costs (80%) Patients treated with everolimus had an estimated life-year gained of 1.273 and QALY of 0.916 over sorafenib, resulting in an ICER of $64,155 per life-year gained or $89,160 per QALY Sensitivity analysis demonstrated that results were robust to parameters of high uncertainty	Everolimus was projected to be a cost-effective treatment relative to sorafenib for patients with advanced RCC who fail sunitinib Estimated ICER fell below the cost per QALY for many oncology medicines in widespread use Compared with sorafenib, everolimus had a high probability of being considered cost-effective at a willingness-to-pay threshold of $100,000 per QALY
Chulikavit et al32 (everolimus, temsirolimus; Novartis Pharmaceuticals)	Model-based analysis to estimate the average monthly cost of treatment of patients with advanced RCC with everolimus vs temsirolimus Drug costs (2009 WAC), drug administration, treatment of underlying disease (physician visits and tests), AEs, and palliative care were included	Average monthly cost	Average monthly costs: Everolimus: $5248 Temsirolimus: $5597 Difference resulted from drug and infusion costs Annual cost-savings of $4188 for treatment with everolimus vs temsirolimus	Everolimus likely provides a less costly treatment option for patients with advanced RCC who fail treatment with sunitinib or sorafenib
Lopes et al33 (everolimus; Novartis Pharmaceuticals)	Excel-based budget impact model for a hypothetical health plan with 1 million members and a prevalence of 203 patients with advanced RCC, where 90% of patients receive treatment	PMPM and PMPY costs	Total cost of drugs, administration, and AE management: Market before everolimus launch (April 2008- March 2009), $7,050,157 Market after everolimus launch (October 2009-September 2010), $6,741,642 Cost-savings of $308,515	The introduction of everolimus as a second-or third-line agent to VEGF-TKI resulted in a minimal budget impact
Vogelzang et al35 Liu et al35 (everolimus, temsirolimus; Novartis Pharmaceuticals)	Retrospective analysis using US Oncology's iKnowMed electronic medical records data from 462 identified patients with mRCC who initiated therapy with everolimus (oral mTOR) or temsirolimus (IV mTOR) Patients followed for 6 months or until treatment discontinuation, whichever occurred earlier	Outpatient visits Inpatient visits Frequency of laboratory assessments	Mean monthly outpatient visits: everolimus 1.19 vs temsirolimus 1.60 (P <.05) Mean monthly laboratory visits: everolimus 1.25 vs temsirolimus 2.23 (P <.05) In multiple regression analyses, temsirolimus was associated with a 28% higher frequency (95% CI, 7%-50%) of outpatient visits and a 58% increased utilization (95% CI, 30%-86%) of laboratory procedures compared with patients receiving everolimus	The oral mTOR inhibitor everolimus is associated with a lower patient burden in terms of outpatient and laboratory visits compared with the IV mTOR inhibitor temsirolimus

AE indicates adverse event; FACT-G, Functional Assessment of Cancer Therapy-General; FKSI, FACT Kidney Symptom Index; ICER, incremental cost-effectiveness ratio; IV, intravenous; mRCC, metastatic renal cell carcinoma; mTOR, mammalian target of rapamycin; OS, overall survival; PFS, progression-free survival; PMPM, per-member per-month; PMPY, per-member per-year; QALY, quality-adjusted life-year; RCC, renal-cell carcinoma; TKI, tyrosine kinase inhibitor; VEGF, vascular endothelial growth factor; VEGFr, vascular endothelial growth factor receptor; WAC, wholesale acquisition cost.