Search

A Markov-based cost-effectiveness model was developed to project long-term effectiveness and costs among patients who undergo nephrectomy for renal cell carcinoma and receive either adjuvant pembrolizumab, adjuvant sunitinib, or routine surveillance alone (no adjuvant treatment). Over a lifetime horizon, pembrolizumab was estimated to prolong quality-adjusted life expectancy and be cost-effective relative to both comparator treatment strategies. Introduction: Pembrolizumab was recently approved as an adjuvant treatment of renal cell carcinoma (RCC), based on prolonged disease-free survival compared to placebo in the phase III KEYNOTE-564 trial. The objective of this study was to evaluate the cost-effectiveness of pembrolizumab as monotherapy in the adjuvant treatment of RCC post-nephrectomy, from a US health sector perspective. Patients and Methods: A Markov model with 4 health states (disease-free, locoregional recurrence, distant metastases, and death) was developed to compare the cost and effectiveness of pembrolizumab versus routine surveillance or sunitinib. Transition probabilities were estimated using patient-level KEYNOTE-564 data (cutoff: June 14, 2021), a retrospective study, and published literature. Costs of adjuvant and subsequent treatments, adverse events, disease management, and terminal care were estimated in 2022 US$. Utilities were based on EQ-5D-5L data collected in KEYNOTE-564. Outcomes included costs, life-years (LYs), and quality-adjusted LYs (QALYs). Robustness was assessed through one-way and probabilistic sensitivity analyses. Results: Total cost per patient was $549,353 for pembrolizumab, $505,094 for routine surveillance, and $602,065 for sunitinib. Over a lifetime, pembrolizumab provided gains of 0.96 QALYs (1.00 LYs) compared to routine surveillance, yielding an incremental cost-effectiveness ratio of $46,327/QALY. Pembrolizumab dominated sunitinib with 0.89 QALYs (0.91 LYs) gained while saving costs. At a $150,000/QALY threshold, pembrolizumab was cost-effective versus both routine surveillance and sunitinib in 84.2% of probabilistic simulations. Conclusion: Pembrolizumab is projected to be cost-effective as an adjuvant RCC treatment versus routine surveillance or sunitinib based on a typical willingness-to-pay threshold. [ABSTRACT FROM AUTHOR]

Background and Objectives: Novel immunotherapy-based combination treatments have drastically improved clinical outcomes for previously untreated patients with advanced/metastatic renal cell carcinoma (aRCC). This study aimed to assess the temporal trends in grade 3/4 adverse event (AE) rates and associated costs of nivolumab plus cabozantinib combination therapy versus sunitinib monotherapy in previously untreated patients with aRCC. Methods: Individual patient data from the CheckMate 9ER trial (nivolumab plus cabozantinib: N = 320; sunitinib: N = 320) were used to calculate the proportion of patients experiencing grade 3/4 AEs. AE unit costs were obtained from the United States (US) 2017 Healthcare Cost and Utilization Project (HCUP) and inflated to 2020 US dollars. Per-patient-per-month (PPPM) all-cause and treatment-related grade 3/4 AE costs over 18-months, temporal trends, and top drivers of AE costs were evaluated in both treatment arms. Results: Overall, the proportion of patients experiencing grade 3/4 AEs decreased over time, with the highest rates observed in the first 3 months for the nivolumab plus cabozantinib and sunitinib arms. Compared with sunitinib, nivolumab plus cabozantinib was associated with consistently lower average all-cause AE costs PPPM [month 3: $2021 vs. $3097 (p < 0.05); month 6: $1653 vs. $2418 (p < 0.05); month 12: $1450 vs. $1935 (p > 0.05); month 18: $1337 vs. $1755 (p > 0.05)]. Over 18 months, metabolism and nutrition disorders ($244), laboratory abnormalities ($182), and general disorders and administration site conditions ($122) were the costliest all-cause PPPM AE categories in the nivolumab plus cabozantinib arm, and laboratory abnormalities ($443), blood and lymphatic system disorders ($254), and metabolism and nutrition disorders ($177) were the costliest in the sunitinib arm. Trends of treatment-related AE costs were consistent with all-cause AE costs. Conclusions: Nivolumab plus cabozantinib was associated with lower costs of grade 3/4 AE management PPPM than sunitinib, which accumulated over the 18-month study period. [ABSTRACT FROM AUTHOR]

Background: The data from the phase III clinical trial KEYNOTE‐426 indicated that pembrolizumab plus axitinib compared with sunitinib could generate clinical benefits in patients with previously untreated advanced renal cell carcinoma (RCC). Given the incremental clinical benefits, we examined the potential cost‐effectiveness of pembrolizumab plus axitinib versus sunitinib in the first‐line setting for patients with advanced RCC from the U.S. payers' perspective. Materials and Methods: Cost and health outcomes were estimated at a willingness‐to‐pay (WTP) threshold of $100,000 to $150,000 per quality‐adjusted life‐year (QALY). One‐way and probabilistic sensitivity analyses were performed by varying potentially modifiable parameters, and additional subgroup analyses were performed as well. Results: Upon our analyses, the total treatment costs in the pembrolizumab plus axitinib and sunitinib groups were $522,796 and $348,424 and the QALYs gained 2.90 and 1.72, respectively. In the base‐case analysis, compared with receiving sunitinib, patients with advanced RCC receiving pembrolizumab plus axitinib gained 1.18 more QALYs at an incremental cost‐effectiveness ratio of $148,676/QALY. The results of subgroup analyses demonstrated that pembrolizumab plus axitinib was most cost‐effective for patients who had one organ with metastasis. Conclusion: First‐line treatment with pembrolizumab plus axitinib, compared with sunitinib, is a cost‐effective strategy when the value of WTP is from $100,000 to $150,000 per QALY in patients with advanced RCC. For patients with one‐organ metastasis and those in International Metastatic Renal Cell Carcinoma Database Consortium poor risk group, first‐line treatment with pembrolizumab plus axitinib is more cost‐effective than others. Implications for Practice: This was the first study to examine the cost‐effectiveness of pembrolizumab plus axitinib versus sunitinib in advanced renal cell carcinoma (RCC). This study found that first‐line treatment with pembrolizumab plus axitinib is a cost‐effective strategy when the value of willingness‐to‐pay is from $100,000 to $150,000 per quality‐adjusted life‐year in patients with advanced RCC from the U.S. payers' perspective. This article examines the cost‐effectiveness of pembrolizumab plus axitinib versus sunitinib in advanced renal cell carcinoma, with the goal of proposing the most cost‐effective strategy with clinical benefit for first‐line therapy in this patient population. [ABSTRACT FROM AUTHOR]

Background/aim: According to the European Society for Medical Oncology (ESMO) and National Comprehensive Cancer Network (NCCN) recommendations, sunitinib is one of the recommended regimens for favorable and intermediate-risk metastatic renal cell carcinoma (mRCC) patients. The objective of this study was to evaluate sunitinib efficacy as a first-line treatment for mRCC patients with favorable/intermediate prognostic risk in a real-world setting., Patients and Methods: Patients diagnosed with mRCC and confirmed as appropriate candidates for the first-line systemic treatment were included in this retrospective study. The prognostic risk was evaluated according to the model of the International Metastatic RCC Database Consortium (IMDC)., Results: Patients received sunitinib as a first-line treatment. A total of 94 patients were enrolled from 2019 to the 2020and 67 of them were included in the detailed analysis. Median progression-free survival (PFS) was 23.4 (95%CI=17.3-29.5), and median overall survival (OS) was 66 months (95%CI=44.9-87.1). The age over 60 years was a significant negative predictor for PFS and OS. Regarding the IMDC model for disease risk prediction, the number of two risk factors in the intermediate risk group was a significant predictor for a shorter response to the first-line therapy., Conclusion: Sunitinib is an effective tyrosine kinase inhibitor, which can be used as a first-line treatment in favorable/intermediate-risk groups of patients with mRCC, especially in countries where novel systemic treatment modalities are not yet available., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Introduction: Pembrolizumab was recently approved as an adjuvant treatment of renal cell carcinoma (RCC), based on prolonged disease-free survival compared to placebo in the phase III KEYNOTE-564 trial. The objective of this study was to evaluate the cost-effectiveness of pembrolizumab as monotherapy in the adjuvant treatment of RCC post-nephrectomy, from a US health sector perspective., Patients and Methods: A Markov model with 4 health states (disease-free, locoregional recurrence, distant metastases, and death) was developed to compare the cost and effectiveness of pembrolizumab versus routine surveillance or sunitinib. Transition probabilities were estimated using patient-level KEYNOTE-564 data (cutoff: June 14, 2021), a retrospective study, and published literature. Costs of adjuvant and subsequent treatments, adverse events, disease management, and terminal care were estimated in 2022 US$. Utilities were based on EQ-5D-5L data collected in KEYNOTE-564. Outcomes included costs, life-years (LYs), and quality-adjusted LYs (QALYs). Robustness was assessed through one-way and probabilistic sensitivity analyses., Results: Total cost per patient was $549,353 for pembrolizumab, $505,094 for routine surveillance, and $602,065 for sunitinib. Over a lifetime, pembrolizumab provided gains of 0.96 QALYs (1.00 LYs) compared to routine surveillance, yielding an incremental cost-effectiveness ratio of $46,327/QALY. Pembrolizumab dominated sunitinib with 0.89 QALYs (0.91 LYs) gained while saving costs. At a $150,000/QALY threshold, pembrolizumab was cost-effective versus both routine surveillance and sunitinib in 84.2% of probabilistic simulations., Conclusion: Pembrolizumab is projected to be cost-effective as an adjuvant RCC treatment versus routine surveillance or sunitinib based on a typical willingness-to-pay threshold., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Studies indicate similar survival and toxicity between pazopanib and sunitinib, but few have examined real-world outcomes among elderly patients with advanced renal cell carcinoma (RCC). The purpose of this retrospective claims analysis was to assess real-world overall survival (OS), healthcare resource utilization (HRU), and healthcare costs (both all-cause and associated with RCC diagnosis) among elderly advanced RCC patients starting pazopanib or sunitinib treatment.Methods: Advanced RCC patients aged 65 years or older who started first-line treatment with pazopanib or sunitinib (index drug; the initiation date was the index date) were identified from the 100% Medicare database plus Part D linkage (January 1, 2006 to December 31, 2014). Patients were stratified by index drug and matched 1:1 with use of propensity scores based on baseline characteristics. OS was assessed from the index date to death and compared by Kaplan-Meier analyses and univariable Cox models; patients were censored at the end of eligibility/data. Monthly HRU and costs from an intent-to-treat perspective were compared by Wilcoxon signed-rank tests.Results: Baseline characteristics were balanced after matching (both N = 522). Treatment with pazopanib was associated with significantly longer median OS compared with treatment with sunitinib (18.2 months vs 14.6 months, respectively; log-rank p = 0.015). Pazopanib was associated with significantly lower monthly all-cause costs compared with sunitinib ($8845 vs $10,416, respectively), as well as lower inpatient costs associated with RCC diagnosis ($1542 vs $2522), fewer monthly inpatient admissions (0.179 vs 0.262), and shorter length of inpatient stay (1.375 days vs 1.883 days; all p ≤ 0.004).Conclusions: Among elderly Medicare patients with advanced RCC, first-line pazopanib tretament was associated with significantly longer OS, as well as lower healthcare costs and HRU, compared with first-line sunitinib treatment. [ABSTRACT FROM AUTHOR]

Background: Sorafenib and sunitinib are oral vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKIs) approved in 2005 and 2006, respectively, for the treatment of patients with renal cell carcinoma (RCC). A population-based, observational cohort study of the cardiovascular risk of VEGFR TKI therapy in elderly RCC patients was conducted.Methods: Using the Surveillance, Epidemiology, and End Results-Medicare database, this study analyzed patients who were 66 years old or older and were diagnosed with RCC from 2000 to 2009. The incidence of cardiovascular adverse events, including congestive heart failure and cardiomyopathy (CHF/CM), acute myocardial infarction (AMI), stroke, and cardiovascular deaths, was examined through December 2010. A Cox proportional hazards model was created to calculate the hazard ratio (HR), and adjustments were made for age, sex, comorbidity, and the use of other systemic therapy.Results: A total of 171 of 670 patients who received sunitinib or sorafenib had cardiovascular events. The incidence rates for CHF/CM, AMI, and stroke were 0.87, 0.14, and 0.14 per 1000 person-days, respectively. Sunitinib or sorafenib use was associated with an increased risk of cardiovascular events (HR, 1.38; 95% confidence interval [CI], 1.02-1.87) and especially stroke (HR, 2.84; 95% CI, 1.52-5.31) in comparison with 788 patients diagnosed with advanced RCC from 2007 to 2009 who were eligible for Part D but did not receive either agent. In subgroup analyses, patients who were 66 to 74 years old at diagnosis had the highest increased risk of stroke associated with the use of either or both drugs.Conclusions: Sunitinib and sorafenib might be associated with an increased risk of cardiovascular events and particularly stroke. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study was to compare treatment characteristics, survival and costs for sunitinib and pazopanib for advanced renal cell carcinoma (RCC) in a real-world setting.Methods: Using claims data, this observational, retrospective cohort study selected individuals aged 19 to 89 years, with commercial or Medicare insurance, advanced RCC, and at least one pharmacy claim for sunitinib or pazopanib between 1 November 2009 and 31 December 2012. Treatment characteristics (treatment interruption, adherence, duration and discontinuation), survival, and costs were measured up to 12 months. Statistical models were adjusted for age, gender, geographic region, race, and RxRisk-V score.Results: At baseline, pazopanib patients exhibited significantly worse health status indicators (RxRisk-V score, number of pharmacy claims, and pre-index total healthcare costs) than sunitinib patients. There were no differences in treatment characteristics or survival. Index medication costs (mean difference $5580, p = 0.03, adj p = 0.05) and total healthcare costs (mean difference $12,192, p = 0.09, adj p = 0.07) trended higher with sunitinib. Patients non-adherent with sunitinib incurred significantly higher total costs compared to patients non-adherent with pazopanib (mean difference $17,680, p = 0.04, adj p = 0.01).Conclusions: Mortality data and proxy variables for treatment effectiveness indicate comparable clinical value for both medications. Sunitinib treatment trended towards higher index medication and total healthcare costs despite higher pre-index total costs and worse health status indicators at baseline with pazopanib. Non-adherence with sunitinib was associated with significantly higher total healthcare costs, which may indicate differences in tolerability between the two agents and requires further investigation. [ABSTRACT FROM AUTHOR]

Abstract: Background: Adhesions represent a major problem after abdominal and pelvic procedures. The purpose of the present study was to determine the effect of sunitinib (Sutent, SU11248), a Food and Drug Administration-approved receptor tyrosine kinase inhibitor, on recurrent pelvic adhesion formation after pelvic adhesiolysis in a rabbit model. Materials and methods: A total of 20 New Zealand white rabbits underwent a uterine abrasion procedure, followed by an adhesiolysis procedure 4 weeks later. Before adhesiolysis, the rabbits were randomized to sunitinib at 10 mg/kg/d or placebo. These were administered as 1 dose preoperatively followed by 10 doses postoperatively. The rabbits were killed 30 d after the adhesiolysis procedure. At death, the adhesions were scored, and a total adhesion score (presented as the median and interquartile range [IQR]) was calculated according to the percentage of uterine involvement and the tenacity of the adhesions. Results: All the rabbits survived the operative procedures without complications. The sunitinib-treated rabbits (n = 10) had a significantly lower uterine involvement score (median 2.0, IQR 1.0–3.0) than the placebo-treated rabbits (median 4.0, IQR 3.0–4.0; P = 0.02). The sunitinib-treated rabbits also had median tenacity score of 3.0 (IQR 3.0–4.0) compared with a median of 4.0 (IQR 4.0–4.0; P = 0.04) in the placebo-treated rabbits (n = 10). The median total score in the sunitinib-treated rabbits was 5.0 (IQR 4.0–6.25) compared with 8.0 (IQR 6.75, 8.0) in the placebo-treated rabbits (P = 0.01). Conclusions: Sunitinib treatment might be an efficacious strategy to reduce recurrent adhesion formation after pelvic procedures. [Copyright &y& Elsevier]

Abstract: Purpose: This study assessed the efficacy and safety of linifanib in patients with advanced renal cell carcinoma (RCC) who were previously treated with sunitinib. Materials and methods: This open-label, multicentre, phase 2 trial of oral linifanib 0.25mg/kg/day enrolled patients who had prior nephrectomy and adequate organ function. The primary end-point was objective response rate (ORR) per response evaluation criteria in solid tumors (RECIST) by central imaging. Secondary end-points were progression-free survival (PFS), overall survival (OS) and time to progression (TTP). Safety was also assessed. Results: Fifty-three patients, median age 61years (range 40–80) were enrolled (August 2007 to October 2008) across 12 North-American centres. Median number of prior therapies was 2 (range 1–4); 43 patients (81%) had clear-cell histology. ORR was 13.2%, median PFS was 5.4months (95% Confidence Interval (CI): 3.6, 6.0) and TTP was the same; median OS was 14.5months (95% CI: 10.8, 24.1). The most common treatment-related adverse events (AEs) were diarrhoea (74%), fatigue (74%) and hypertension (66%), and the most common treatment-related Grade 3/4 AE was hypertension (40%). Conclusions: Linifanib demonstrated clinically meaningful activity in patients with advanced RCC after sunitinib failure. At 0.25mg/kg/day, significant dose modifications were required. An alternative, fixed-dosing strategy is being evaluated in other trials. [Copyright &y& Elsevier]

Abstract: A sensitive, precise and accurate quantitative liquid chromatography/tandem mass spectrometry (LC–MS/MS) method for the measurement of sunitinib (SU11248) and N-desethyl sunitinib (SU12662) in human plasma was developed and validated. All sample handling was done under strict light protection. The sample preparation method employed acetonitrile protein precipitation using d 5-SU11248 as an internal standard. The processed samples were chromatographed on a polymeric reversed-phase analytical column and analyzed by triple-quadrupole MS/MS in multiple reaction monitoring (MRM) mode using positive TurboIonSpray® (TISP). The LC–MS/MS method described in this paper presents high absolute recovery (86.2% SU11248, 84.8% SU12662), high sensitivity (lower limit of quantitation of 0.06ng/mL for both analytes), high inter-day precision (1.6–6.1% SU11248, 1.1–5.3% SU12662) and high analytical recovery (99.8–109.1% SU11248, 99.9–106.2% SU12662), as well as excellent linearity over the concentration range 0.060–100ng/mL (r 2 >0.999) with a short runtime of only 4.0min. Results on the stability of SU11248 and SU12662 in human plasma are presented. During validation plasma from intensive care patients receiving many drugs were tested for interference and incurred samples were analyzed. The method met all criteria of the EMA and FDA guidelines during validation and was successfully applied to a pharmacokinetic study in healthy human volunteers. [Copyright &y& Elsevier]

Background: In a randomised phase III trial, sunitinib significantly improved efficacy over interferon-alpha (IFN-alpha) as first-line therapy for metastatic renal cell carcinoma (mRCC). We report the final health-related quality of life (HRQoL) results.Methods: Patients (n=750) received oral sunitinib 50 mg per day in 6-week cycles (4 weeks on, 2 weeks off treatment) or subcutaneous IFN-alpha 9 million units three times weekly. Health-related quality of life was assessed with nine end points: the Functional Assessment of Cancer Therapy-General and its four subscales, FACT-Kidney Symptom Index (FKSI-15) and its Disease-Related Symptoms subscale (FKSI-DRS), and EQ-5D questionnaire's EQ-5D Index and visual analogue scale. Data were analysed using mixed-effects model (MM), supplemented with pattern-mixture models (PMM), for the total sample and the US and European Union (EU) subgroups.Results: Patients receiving sunitinib reported better scores in the primary end point, FKSI-DRS, across all patient populations (P<0.05), and in nine, five, and six end points in the total sample, in the US and EU groups respectively (P<0.05). There were no significant differences between the US and EU groups for all end points with the exception of the FKSI item 'I am bothered by side effects of treatment' (P=0.02). In general, MM and PMM results were similar.Conclusion: Patients treated with sunitinib in this study had improved HRQoL, compared with patients treated with IFN-alpha. Treatment differences within the US cohort did not differ from those within the EU cohort. [ABSTRACT FROM AUTHOR]

Treatment with cytotoxic chemotherapy has reached a therapeutic plateau in advanced-stage non-small cell lung cancer (NSCLC), and the development of anti-angiogenesis therapy has become an area of intense investigation. Bevacizumab, a monoclonal antibody against vascular endothelial growth factor (VEGF), is approved in combination with platinum-based therapy for the treatment of patients with non-squamous advanced-stage NSCLC in Europe and the United States. Patients with brain metastases were previously considered ineligible for treatment with bevacizumab, but a recent phase II trial has demonstrated a low rate of central nervous systemhemorrhage, and treated brain metastases are no longer considered a contraindication to bevacizumab. Oral multitargeted tyrosine kinase inhibitors that target the VEGF receptors are also in development. To date, the common toxicities observed with these agents include nausea/vomiting, hypertension, diarrhea, fatigue, and rash, including hand-foot syndrome. Three phase III trials have been performed to investigate the activity of vandetanib, an oral inhibitor of VEGF receptors and epidermal growth factor receptor (EGFR). A higher response rate, longer progression-free survival (PFS; the primary endpoint), and improved time to deterioration of symptoms was observed in the vandetanib and docetaxel combination arm compared to docetaxel in patients who were receiving second-line therapy; a statistically significant improvement in overall survival was not observed. A significant difference in PFS was not observed in the two other phase III trials investigating vandetanib. This agent is not commercially available in Europe or the United States. Phase III trials of sorafenib, sunitinib, BIBF 1120, and cediranib in advanced NSCLC are ongoing. [ABSTRACT FROM AUTHOR]

The article discusses the efficacy of sorafenib and sunitinib therapy to patients with renal cell cancer (RCC). The U.S. Food and Drug Administration (FDA) has approved the pharmaceutical drugs due to its small molecule inhibitors of multiple intracellular and receptor protein kinases which could control tumor growth and angiogenesis. Information regarding the clinical indications, pharmacokinetics and therapeutic effects of the therapy is also presented.

Recent advances in the understanding of the pathogenesis of cancer have led to the introduction of a variety of biological agents with novel mechanisms of action into clinical trials and even into clinical practice. In particular, tumour-associated neoangiogenesis has become a major target for this new class of antineoplastic agents. Five anti-angiogenic agents (thalidomide, lenalidomide, bevacizumab, sunitinib, sorafenib) have already obtained US Food and Drug Administration approval for clinical use, and many others have entered clinical trials. Many new biological agents with anti-angiogenic properties appear to be associated with an increased risk for thrombosis and, paradoxically, bleeding. Although the mechanisms underlying the increased thromboembolic risk remain ill defined, the main hypothesis is that perturbation of tumour-associated endothelial cells can switch the endothelium from a naturally anticoagulant surface to a prothrombotic surface, thus mediating the activation of systemic coagulation in cancer patients, who are already more susceptible to thromboembolism due to their underlying disease. The toxicity profile differs between the anti-angiogenic agents. Thalidomide, lenalidomide, semaxibin (SU5416) and prinomastat have produced more venous thromboembolic complications, whereas bevacizumab, sunitinib, sorafenib and ZD6126 have been associated with a higher risk of arterial thromboembolism and, in particular, myocardial ischaemia. The observation of these vascular toxicities suggests the need to establish, in randomized clinical trials, the usefulness of thrombosis prophylaxis when anti-angiogenic agents are used in cancer patients, especially when associated with chemotherapy. In addition, careful reporting of haemostatic complications during treatment with new anti-angiogenic drugs is warranted. [Copyright &y& Elsevier]

The understanding of cellular processes underlying tumour biology has allowed the development of novel molecular-targeted drugs with optimistic results in renal cell carcinoma (RCC). Mutations in the von Hippel-Lindau gene are found in 75% of sporadic RCCs, which results in upregulation of several genes involved in angiogenesis, e.g. vascular endothelial growth factor and platelet-derived growth factor. Other activated pathways in RCC are the epidermal growth factor receptor and the mTOR pathway, which regulate survival and cell growth. In addition to temsirolimus (an mTOR inhibitor) two different strategies have been studied to inhibit these targets: monoclonal antibodies, e.g. bevacizumab, and small molecule tyrosine-kinase inhibitors such as sorafenib, sunitinib and AG 013736. Phase II studies with these drugs reported substantial clinical activity in advanced RCC. Survival benefit was reported with temsirolimus, sunitinib and sorafenib in randomized trials, which led to the accelerated approval of sorafenib and sunitinib for advanced RCC by regulatory authorities in the USA and Europe. Nevertheless, as new therapies develop, new challenges arise for the optimum use of these targeted drugs. We discuss the rationale and the clinical development of these novel molecular-targeted agents, with special emphasis on updated information presented at recent meetings because of the relevance of the data reported and the potential future impact in the management of patients with RCC. [ABSTRACT FROM AUTHOR]

This perspective biases on the side that personalized medicine can contribute to a more efficient collective model; however, the hard economics need and deserve significantly more critical analysis and new data input than they are currently being given, to determine their role, or not, in driving change. Put simply, as with the birth of all new and promising developments in healthcare, myth, hope and trend-spotting are driving this market forward, rather than any hard evidence of a sustainable commercial business model for all stakeholders. While there are clear economic benefits to aspects of delivery along the way to personalized care, there may in fact be no compelling economic drivers for radical change for payers and the pharmaceutical industry. The best they can hope to achieve is that the balance sheet is, just that, in balance. [ABSTRACT FROM AUTHOR]

Background: Despite the rapid approval of targeted therapies for metastatic renal cell carcinoma (mRCC) evidence on real world treatment patterns remains limited. This study evaluated patterns of first-line targeted therapy utilization and adherence in older adults, a population with a high burden of RCC., Methods: 2093 patients aged ≥66 years with a primary diagnosis of mRCC were identified from United States (US)-based cancer registry and administrative claims data (2007-2015). We included only patients with de novo disease. We assessed the initiation of first-line targeted therapy within four months of diagnosis and persistence and adherence to targeted therapy, using the proportion of days covered (PDC). Multivariable logistic regression yielded adjusted odds ratios (ORs) and 95% confidence intervals (CIs) to describe characteristics associated with targeted therapy versus no targeted therapy initiation and for high (≥80% PDC) versus low adherence., Results: 28.8% of patients received first-line targeted therapy within four months of diagnosis, with the proportion of patients receiving targeted therapy increasing over time. Older age (one-year increment OR:0.95 95%CI 0.93, 0.97), high comorbidity burden (OR:0.65 95%CI0.46, 0.93) and clear cell histology (OR:1.54 95%CI 1.19, 2.00) were associated with targeted therapy initiation. 48.2% of patients exhibited a high PDC to oral targeted therapy at 120 days, which was attenuated with inclusion of patients who died during the time period (34.2% PDC ≥80%)., Conclusion: Increasing age, high comorbidity burden and non-clear cell histology were associated with decreased targeted therapy initiation among patients with de novo mRCC. Our findings suggest adherence to oral therapies was low; future research exploring the mechanisms and impact of low adherence in this older patient population is warranted., Competing Interests: Declaration of Competing Interest Dr. Lund's spouse is a full-time, paid employee of and owns stock in GlaxoSmithKline. She also receives research support from AbbVie, Inc. for an unrelated research study. Ms. Chun is a pre-doctoral fellow at Bristol Meyers Squibb. Dr. Tan receives funding from the American Cancer Society. Dr. Hicks receives funding from Cancer Research UK., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: The median age at renal cell carcinoma (RCC) diagnosis is 64 years. However, few studies have assessed the real-world time on treatment (TOT), health resource utilization (HRU), costs, or treatment compliance associated with targeted therapy use among patients in this age group with RCC., Objective: To assess the HRU, costs, and compliance during TOT among Medicare patients aged ≥ 65 years with advanced RCC (aRCC) who initiated first targeted therapy with pazopanib or sunitinib., Methods: Patients with aRCC were identified in the 100% Medicare + Part D databases administered by the Centers for Medicare & Medicaid Services. Eligible patients initiated first targeted therapy with sunitinib or pazopanib (index drug) on or after their first diagnosis of secondary neoplasm between October 19, 2009, and January 1, 2014, and were aged ≥ 65 years as of 1 year before first targeted therapy initiation (index date). Included patients were stratified into pazopanib and sunitinib cohorts based on first targeted therapy and matched 1:1 on baseline characteristics using propensity scores. TOT was defined as the time from the index date to treatment discontinuation (prescription gap > 90 days) or death. Compliance was defined as the ratio of drug supply days to TOT. Monthly all-cause costs and costs associated with RCC diagnosis (medical and pharmacy in 2015 U.S. dollars) and HRU (inpatient [admissions, readmissions, and days], outpatient, and emergency room visits) were assessed in the 1-year post-index period during TOT. Matched cohorts' TOT was compared using Kaplan-Meier analyses and univariable Cox models, and compliance, HRU, and costs were compared using Wilcoxon signed-rank tests., Results: Of 1,711 included patients, 526 initiated pazopanib and 1,185 initiated sunitinib. Before matching, more patients in the pazopanib cohort were white, diagnosed in 2010-2014 versus 2006-2009, and had lung metastases compared with the sunitinib cohort (all P < 0.05). The pazopanib cohort also had higher mean outpatient visits and costs but lower mean total all-cause pharmacy costs, than the sunitinib cohort (all P < 0.05). After matching, the pazopanib and sunitinib cohorts had similar characteristics (mean age 75 years, 58% male, and Charlson Comorbidity Index score of 9.2 in both cohorts) and median TOT (4.8 and 4.1 months, respectively). Among the 522 matched pairs, pazopanib was associated with significantly lower total all-cause health care costs ($8,527 vs. $10,924, respectively [mean difference = $2,397]); total medical costs ($3,991 vs. $5,881, respectively, [$1,890]); and inpatient costs ($2,040 vs. $3,731, respectively, [$1,692]; all P < 0.01) compared with sunitinib. Patients receiving pazopanib had significantly fewer inpatient admissions (0.179 vs. 0.289, respectively) and days (1.063 vs. 1.904, respectively; both P < 0.01) than patients receiving sunitinib. Mean treatment compliance was lower for the pazopanib versus sunitinib cohort (0.91 vs. 0.94, respectively; P < 0.01)., Conclusions: In this retrospective analysis of Medicare patients with aRCC from a TOT perspective, first targeted therapy with pazopanib was associated with significantly lower all-cause health care costs and HRU, but lower compliance, compared with sunitinib., Disclosures: Funding for this research was provided by Novartis Pharmaceuticals. The sponsor was involved in all stages of the study's conduct and reporting. Vogelzang has been a consultant for Novartis, Amgen, Celgene, Medivation, Eisai, Exelixis, and Roche; has spoken at Novartis, Astellas, Johnson and Johnson, Pfizer, Dendreon, Bayer/Algeta, GSK, and Veridex/Janssen; and has received research support from Novartis, Bayer, Exelixis, Progenics, Bavarian Nordic, and Viamet. Pal has been a consultant for Novartis, Pfizer, Aveo, Dendreon, and Myriad and has spoken at Novartis, Pfizer and Medivation. Agarwal has been a consultant or advisor for Novartis, Pfizer, Exelixis, Cerulean Pharma, Medivation, Eisai, and Argos Therapeutics. Swallow, Peeples, Zichlin, and Meiselbach are employees of Analysis Group, which received consultancy fees from Novartis for this project. Li was an employee of Analysis Group during the conduct of this study. Ghate is an employee of Novartis and owns stock/stock options. Perez was an employee of Novartis during the conduct of this study. A synopsis of the economic outcomes was presented at the Academy of Managed Care Pharmacy Nexus 2017 in Denver, Colorado, during March 27-30, 2017. A synopsis of the clinical outcomes was presented at the 22nd ISPOR Annual International Meeting in Boston, Massachusetts, during May 20-24, 2017.

Background: Despite existing guidelines for first-line treatment of metastatic renal cell carcinoma (mRCC), prescribing preferences in the United States have not been fully examined. The objectives of this study were to characterize US physicians' preferences and factors influencing first-line mRCC treatment., Materials and Methods: A Web-based study presented physicians with hypothetical mRCC patient cases and recorded initial therapy preference and rationale. Descriptive statistics were used to characterize preferred treatment; logistic regression was used to determine patient characteristics associated with therapy changes. Analyses were conducted on pooled responses across cases. Model results were summarized using odds ratios (ORs), 95% confidence intervals, and P values for the covariates., Results: One hundred nine physicians participated in the study; 96 (88.1%) chose a tyrosine kinase inhibitor as their preferred first-line mRCC treatment (62 [56.9%], sunitinib; 31 [28.4%], pazopanib). Perceived superior overall survival and progression-free survival were top reasons physicians chose sunitinib; enhanced tolerability and efficacy similar to sunitinib were top reasons physicians chose pazopanib. Initial sunitinib prescribers were more likely to change therapy in the presence of comorbid conditions (OR, 2.915; P = .0068), poor Eastern Cooperative Oncology Group performance status (OR, 2.368; P = .0106), or poor prognostic risk (OR, 3.884; P = .0224). This was not seen for initial pazopanib prescribers., Conclusion: Sunitinib and pazopanib were the most preferred agents for first-line mRCC treatment. Sunitinib preference was driven by perceptions of efficacy, and pazopanib was preferred for its perceived tolerability and efficacy similar to sunitinib. With varying clinical scenarios, initial pazopanib prescribers were more likely to maintain pazopanib and alter dosing; sunitinib prescribers were more likely to switch therapy., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Advanced thyroid cancer is not amenable to therapy with conventional cytotoxic chemotherapy. However, newer advances in the understanding of the molecular pathogenesis of different subtypes of thyroid cancer have provided new opportunities for the evaluation of molecularly targeted therapies. This has led to multiple clinical trials using various multi-kinase inhibitors and the subsequent US FDA approval of sorafenib for differentiated thyroid cancer and vandetanib and cabozantinib for medullary thyroid carcinoma. This review provides a summary of the current literature for the treatment of advanced thyroid carcinoma and future directions in this disease.

Background: For first-line therapy options for advanced renal cell carcinoma (RCC), clinical trials have demonstrated similar efficacy for pazopanib and sunitinib as well as differing side-effect profiles, which may affect patient persistence in self-administration of these oral medications. However, the treatment patterns of each drug in real-world clinical practice, as opposed to the controlled environment of a trial, have not been directly compared., Objective: To compare persistence and compliance (adherence) with pazopanib versus sunitinib in a real-world setting., Methods: This was a retrospective claims analysis using 2 databases: Optum Research Database and Impact National Benchmark Database. Eligible patients included adult patients (aged ≥ 18 years) with ≥ 2 RCC diagnoses and evidence of first-line therapy with ≥ 1 subsequent pharmacy claim for pazopanib or sunitinib between October 2009 and July 2012. The date of the first pazopanib or sunitinib claim was defined as the index date. Additional requirements included continuous enrollment in the health plan for 2 months prior (baseline period) through 6 months after (follow-up period) the index date and no cancers other than those associated with RCC. Propensity score matching was used to minimize selection bias. Persistence with the index drug was compared using days to discontinuation, estimated level of persistence (ELPT) at 180 days, and proportion of days covered (PDC). PDC was defined by dividing the number of days covered with the index drug by the number of follow-up days. Compliance was estimated using medication possession ratio (MPR). For matched cohort pairs with > 1 fill, MPR was defined by dividing the number of days covered with the index drug by the number of days between the first and last index medication fill., Results: We identified 84 matched pairs among 97 patients prescribed pazopanib and 349 prescribed sunitinib. Among the matched population, mean comorbidity index score was 5.8 (95% CI = 1.8-6.0) for pazopanib, and 6.1 (95% CI =1.8-6.0) for sunitinib (P = 0.133). Evidence of any radiation therapy during the baseline period was significantly higher among the sunitinib cohort prior to matching (9% vs. 18%, P = 0.043), and evidence of surgery was higher in the pazopanib cohort after matching (12% vs. 7%, P = 0.046). Cohorts were balanced according to demographic and clinical characteristics with mean (SD) age of 63.0 (9.0) years and 77.4% male. During the 6-month period after drug initiation, there was no significant difference (P > 0.05) by drug cohort in the duration of index drug therapy or the percentage of patients who discontinued their index drugs. The mean (SD) time to discontinuation was 133.4 (62.8) days and 139.9 (55.6) days among the matched pazopanib and sunitinib cohorts, respectively (P = 0.445). In both cohorts, more than 40% of patients discontinued their index drugs (46.4% pazopanib and 44.1% sunitinib, P = 0.732). In addition, there was no significant difference by drug cohort in the ELPT at any time examined between 30 and 180 days after initiation of therapy. PDC with the index drug during the fixed 6-month follow-up was also examined. Although the mean PDC was significantly higher among the sunitinib cohort (0.77 vs. 0.68 for pazopanib, P = 0.037), there was no difference by cohort in the percentage of patients with high PDC (defined as ≥ 80%): 52.4% versus 56.0% for pazopanib and sunitinib, respectively (P = 0.622). Mean MPR among matched pairs with at least 2 fills for the index drug was significantly higher among the sunitinib cohort, although there was no difference by cohort in the percentage of patients with high MPR (defined as ≥ 80%): 81.4% versus 93.2% for pazopanib and sunitinib, respectively (P > 0.071)., Conclusions: In the first 6 months of treatment, persistence and compliance to pazopanib and sunitinib were similar. Future studies are needed, including those assessing larger cohorts and longer follow-up periods.

Background: Pazopanib was noninferior to sunitinib in progression-free survival in a phase III, open-label, randomized clinical trial comparing the efficacy and safety of the 2 drugs for treatment of patients with advanced renal cell carcinoma (RCC). A secondary analysis of this trial conducted on patient-reported health care resource utilization (HCRU) endpoints revealed significantly fewer monthly telephone consultations and emergency department visits among patients treated with pazopanib over the first 6 months of treatment., Objectives: To (a) compare total costs of HCRU and adverse events (AEs) in patients with advanced RCC receiving first-line pazopanib or sunitinib from the phase III clinical trial and (b) perform a post hoc economic analysis that applied direct medical care and pharmacy unit costs, obtained from the Truven Health MarketScan Databases, to HCRU and AE rates., Methods: Total HCRU costs included components for provider contacts, diagnostics, hospitalizations, procedures, and study/nonstudy drugs. Patients were stratified by the presence or absence of an AE in order to estimate costs attributable to AEs. Costs were adjusted to 2013 U.S. dollars. The highest 1% of cost outliers were equally excluded from each group. Univariate (t-test and Kaplan-Meier sample average [KMSA]) and multivariate (using treatment group and region as covariates) analyses were performed., Results: A total of 906 patients (pazopanib, n = 454; sunitinib, n = 452) reported HCRU; higher rates were observed for sunitinib. In unadjusted cost analyses, the mean total costs for pazopanib-treated patients were 8.0% lower than those treated with sunitinib ($80,464 vs. $86,886; P = 0.20). The difference in KMSA-estimated costs was significantly higher for sunitinib versus pazopanib ($156,128 vs. $143,585; P = 0.003). Adjusted cost differences between arms consistently suggested higher costs for sunitinib. Among patients who experienced greater than or equal to 1 AE, costs were $8,118 higher for pazopanib-treated patients and $14,343 for sunitinib-treated patients., Conclusions: The findings suggest that health care costs were lower among patients with advanced RCC treated first-line with pazopanib versus sunitinib.

Background: Current first-line treatments for metastatic renal cell carcinoma (mRCC) include the multityrosine kinase inhibitors pazopanib and sunitinib. Both agents had similar progression-free survival (PFS) and overall survival (OS) in the COMPARZ trial (Comparing the Efficacy, Safety and Tolerability of Pazopanib versus Sunitinib); however, the adverse event profiles of the 2 agents are different. In the PISCES trial (Patient Preference Study of Pazopanib versus Sunitinib in Advanced or Metastatic Kidney Cancer), patients and physicians preferred pazopanib primarily because it offered better health-related quality of life (HRQoL) and caused less fatigue., Objective: To compare the cost-effectiveness of pazopanib versus sunitinib from a U.S. health care system perspective in the first-line treatment of patients with mRCC., Methods: A partitioned-survival analysis model with 3 health states (preprogression, postprogression, and dead), data from 2 randomized controlled trials of pazopanib versus sunitinib (COMPARZ and PISCES), and secondary sources were used to calculate the incremental cost per quality-adjusted life-year (QALY) gained for pazopanib versus sunitinib. A time horizon of 37.5 months was used in the base case, consistent with the duration of follow-up used in the COMPARZ trial. The proportion of patients in each health state over time was based on Kaplan-Meier survival distributions for PFS and OS from the COMPARZ trial. Utility values were obtained from the PISCES trial. Costs were based on medical resource utilization data from the COMPARZ trial and unit costs from secondary sources. Probabilistic sensitivity analyses and deterministic sensitivity analyses were conducted., Results: In the base case, pazopanib was estimated to provide more QALYs at a lower cost compared with sunitinib (pazopanib dominant). In probabilistic sensitivity analyses, pazopanib was projected to be dominant in 69% of the simulations. The probability that pazopanib was more cost-effective than sunitinib was ≥ 90% for threshold values of cost-effectiveness between the range of $10,000-$160,000 per QALY gained. In deterministic sensitivity analyses, pazopanib was dominant in all scenarios examined., Conclusion: Results of this study suggest that pazopanib is cost-effective compared with sunitinib as the first-line treatment of patients with mRCC in the United States.

Study Type - Therapy (economic) Level of Evidence 2b What's known on the subject? and What does the study add? Cost-effectiveness of new targeted molecular therapies in patients with mRCC have been examined compared to interferon-α. This study compares cost-effectiveness of three new targeted therapies in mRCC head-to-head based on indirect comparison of clinical efficacy. The study shows that sunitinib is a cost-effective therapy in first line treatment for patients with mRCC in the USA and Sweden compared to sorafenib and bevacizumab+interferon-α. OBJECTIVE • To assess the economic value of targeted therapies as first-line metastatic renal cell carcinoma (mRCC) treatment in the US and Sweden by indirect comparison of survival data. METHODS • A Markov model simulated disease progression, adverse events and survival with sunitinib vs sorafenib in the US and bevacizumab plus interferon-α (IFN-α) in both countries. • Results, in life-years (LYs), progression-free LYs (PFLYs), quality-adjusted LYs (QALYs) gained and treatment costs (2008 USD) were obtained through deterministic and probabilistic analyses over the patient's lifetime. RESULTS • Sunitinib was more effective and less costly than sorafenib (gains of 0.52 PFLYs, 0.16 LYs and 0.17 QALYs and savings/patient of $13 576 in the US) and bevacizumab plus IFN-α (gains of 0.19 PFLYs, 0.23 LYs and 0.16 QALYs in both countries and savings/patient of $67 798 and $47 264 in the US and Sweden, respectively). • Results were most influenced by hazard ratios for progression-free and overall survival and treatment costs, making results generalizable across other countries if relative costs were to fall within the ranges of those in the US and Sweden. CONCLUSION • The present analyses suggest that first-line mRCC treatment with sunitinib is a cost-effective alternative to sorafenib and bevacizumab plus IFN-α. [ABSTRACT FROM AUTHOR]

Background: Limited information on real-world treatment patterns of targeted agents for metastatic renal cell carcinoma (mRCC) is available to inform their use in clinical practice., Patients and Methods: This retrospective observational study used US claims data (from January 2007 to November 2010) to identify treatment patterns, including treatment duration and dosing, for molecular-targeted agents (sunitinib, sorafenib, pazopanib, bevacizumab, and temsirolimus) indicated in first-line management of advanced and/or mRCC. The study included adult patients with mRCC who were observable for ≥3 months after initiation of their first-line therapy with a targeted agent. Descriptive analyses were conducted for observed treatment patterns., Results: Of the 273 patients on first-line therapy identified and included in the sample, 235 patients were treated with sunitinib, 16 patients with sorafenib, and 15 patients with temsirolimus. Pazopanib and bevacizumab were excluded from the analysis due to the small sample size, n < 10. The median observed treatment durations were sunitinib 98 days, sorafenib 121 days, and temsirolimus 78 days. Approximately 76% (178/235) of patients who received sunitinib initiated therapy at the indicated dose of 50 mg; 65% of these patients were not observed filling a fourth prescription, whereas 23% maintained their starting dose and 12% experienced dose reduction at their 4+ fill. The mean starting dose for patients who initiated on sorafenib (n = 16) was 725 mg and for temsirolimus (n = 15) was 25 mg: their study samples were insufficient for further, meaningful dosing analyses., Conclusions: Results of this study suggest that opportunities exist to improve treatment duration in clinical practice and to better understand influences on treatment and dose changes., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Safety and treatment patterns of sunitinib and sorafenib in metastatic renal cell carcinoma (mRCC) had been previously reported using retrospective chart review of patients treated in US tertiary centers. Because practice patterns may vary between hospital- and office-based settings, this study examined safety and treatment patterns of these agents in US community oncology clinics. Medical records were retrospectively reviewed for 250 patients with mRCC treated at 18 community oncology clinics. Eligible patients were ≥18 years old and received ≥1 prescription for sunitinib (n = 131) or sorafenib (n = 119) as first-line anti-angiogenic treatment. Rates of adverse events (AEs) and treatment modifications were analyzed; reasons for treatment modifications were examined. Median duration of first-line sunitinib and sorafenib treatment was 5.9 and 5.5 months, respectively. Among patients treated with sunitinib and sorafenib, 86% (30%) and 87% (28%), respectively, experienced ≥1 all-grade (grade 3/4) AE. The most common AEs were fatigue/weakness in sunitinib (all-grade: 42%; grade 3/4: 5%) and skin rash in sorafenib (all-grade: 35%; grade 3/4: 6%). Sixty-two and 64% of patients treated with sunitinib and sorafenib, respectively, had ≥1 treatment modification due to AEs. Recorded AE rates in patients with mRCC treated with angiogenesis inhibitors in community practice tended to be lower than in tertiary centers, possibly due to shorter treatment duration. Rates of treatment modifications due to AEs tended to be higher in community practice. This study provides evidence from an office-based setting of unmet need for agents that may provide improved tolerability in mRCC.

Treatment options for renal cell carcinoma have changed dramatically since 2005 when the U.S. Food and Drug Administration approved six new therapies. These agents inhibit pathways relevant in the pathogenesis of renal cell carcinoma, interfering with tumor angiogenesis, cell progression, and metastasis. Understanding the pharmacology of these agents is necessary for clinicians to provide appropriate patient education, assure adherence with the treatment plan, and facilitate early identification and intervention for side effects. These activities will provide positive clinical outcomes.