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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.)

Background: In a phase 3, randomized, open-label trial (Pazopanib versus Sunitinib in the Treatment of Locally Advanced and/or Metastatic Renal Cell Carcinoma, COMPARZ; NCT00720941), pazopanib was found to be noninferior to sunitinib in terms of progression-free survival in patients with metastatic renal cell carcinoma with no prior therapy. Overall treatment differences were evaluated in a post hoc analysis with a quality-adjusted time without symptoms or toxicity (Q-TWiST) methodology., Methods: Each patient's overall survival was partitioned into 3 mutually exclusive health states: time with grade 3 or 4 toxicity (TOX), time without symptoms of disease or grade 3/4 toxicity of treatment, and time after tumor progression or relapse (REL). The time spent in each state was weighted by a health-state utility associated with that state and summed to calculate the Q-TWiST. A threshold utility analysis was used, and utilities were applied across the range of 0 (similar to death) to 1 (perfect health)., Results: A total of 1110 patients were enrolled (557 on pazopanib and 553 on sunitinib). The mean TOX was 31 days (95% confidence interval, 13-48 days) longer for sunitinib versus pazopanib. In the threshold utility analysis, the difference in the Q-TWiST ranged from -11 days (utility for TOX, 1; utility for REL, 0) to 43 days (utility for TOX, 0; utility for REL, 1) in favor of pazopanib across most utility combinations. Differences were significant in less than half of the utility combinations examined, and this typically occurred when the utility for TOX was lower than the utility for REL., Conclusions: Patients randomized to pazopanib had a slightly longer Q-TWiST in comparison with sunitinib patients, and this was primarily due to the reduced length of TOX., Competing Interests: Information Summary: Jennifer L. Beaumont Received grants from GlaxoSmithKline for the conduct of the study and personal fees from GlaxoSmithKline, Gilead, and Ipsen outside the submitted work. John M. Salsman Reports other (support for manuscript writing) from GlaxoSmithKline during the conduct of the study. Jose Diaz Was employed by GlaxoSmithKline and Novartis, and owned stock in GlaxoSmithKline. Keith Deen Was employed by GlaxoSmithKline and owned stock in GlaxoSmithKline. Lauren McCann Was employed by GlaxoSmithKline and owned stock in GlaxoSmithKline. Thomas Powles Reports personal fees from Roche, Novartis and Pfizer outside the submitted work. Michelle D. Hackshaw Reports employment (former) by and stock ownership in GlaxoSmithKline. Robert J. Motzer Reports grants from GlaxoSmithKline during the conduct of the study; grants and personal fees from Novartis and Pfizer outside the submitted work. David Cella Reports personal fees from GlaxoSmithKline outside the submitted work., (© 2016 American Cancer Society.)

Background: Several systemic therapies are now approved for first- and second-line treatment of metastatic renal cell carcinoma (mRCC). Although the National Comprehensive Cancer Network (NCCN) guidelines offer physicians evidence-based recommendations for therapy, there are few real-world studies to help inform the utilization of these agents in clinical practice., Objectives: To (a) describe the patterns of use associated with systemic therapies for mRCC among Humana members in the United States diagnosed with mRCC, (b) assess consistency with the NCCN guidelines for treatment, and (c) to describe the initial first-line therapy regimen by prescriber specialty and site of care., Methods: This was a retrospective study using Humana's claims database of commercially insured patients and patients insured by the Medicare Advantage Prescription Drug plan. The study period was from January 1, 2007, to December 31, 2013. Patients with mRCC were identified by ICD-9-CM codes 189.0/189.1 and 196.xx to 199.xx; all patients were between 18 and 89 years of age, had received systemic therapy for their disease, and were followed up for 180 days. Outcome measures included choice of initial systemic therapy, starting and ending doses, first-line treatment persistence and compliance, and choice of second-line therapy. Persistence was measured using time to discontinuation of first-line therapy and proportion of days covered (PDC; the ratio of [total days of drug available minus days of supply of last prescription] to [last prescription date minus first prescription date]). Compliance was measured using the medication possession ratio (MPR; the ratio of [total days supply minus days supply of last prescription] to [last prescription date minus first prescription date])., Results: A total of 649 patients met all inclusion criteria; 109 were insured by commercial plans and 540 were insured by Medicare. The mean ± SD age of patients was 68.6 ± 9.4 years, and 68.6% were male; Medicare patients were older than commercial patients (71.7 ± 7.4 vs. 56.6 ± 9.1 years, respectively; P < 0.001). The most common comorbidities among the patient population were hypertension, hyperlipidemia, diabetes, and heart disease. The majority of patients (68.6%) received an oral tyrosine kinase inhibitor (TKI) as their first line of therapy: 43.9% received sunitinib, 14.0% received sorafenib, 10.0% received pazopanib, and 0.6% received axitinib. Mean ± SD time to discontinuation of first-line TKI treatment was 169.1 ± 29.5 days with sunitinib, 160.3 ± 41.1 days with pazopanib, and 160.1 ± 41.4 days with sorafenib. Other first-line therapies included inhibitors of mammalian target of rapamycin (mTOR) (19.7%) and the antivascular endothelial growth factor agent bevacizumab (9.4%). Among patients receiving mTOR inhibitors, 14.8% were started on temsirolimus and 4.9% were started on everolimus. The median starting and ending doses were the same for each drug except for sunitinib. Mean ± SD times to discontinuation of temsirolimus, everolimus, and bevacizumab were 171.8 ± 26.2, 137.0 ± 62.2, and 150.8 ± 56.0 days, respectively. Persistence on first-line regimen as measured by PDC was high (PDC ≥ 80%) for 89% of oral therapies and 77% of injectable therapies; first-line compliance was high (MPR ≥ 80%) for 77% of oral therapies and 68% of injectables. Among patients who received second-line therapy, the most common regimen was everolimus (29.2%), followed by bevacizumab (19.8%), temsirolimus (15.6%), and sunitinib (13.6%). Specialty codes obtained from the database provider identified internal medicine specialists and oncologists as the most common prescribers of TKIs and mTOR inhibitors., Conclusions: Patterns of use were similar for each of the prescribed systemic treatments for mRCC, and the majority of patients were highly persistent and compliant with first-line therapies. Time to treatment discontinuation was slightly longer with oral agents compared with injectable drugs.

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: Clinical trials have demonstrated that pazopanib prolongs progression-free survival (PFS), with an acceptable safety profile, for patients with advanced renal cell carcinoma (aRCC). The efficacy of second-line mammalian target of rapamycin (mTOR) inhibitors in pazopanib-treated patients has also been evaluated in clinical trials; however, few studies have evaluated first-line pazopanib or second-line mTOR inhibitors in real-world settings. The present study evaluated the outcomes of first-line pazopanib, and pazopanib followed by mTOR inhibitors, in a community oncology setting., Patients and Methods: The present study was a retrospective analysis of eligible patients in US Oncology's iKnowMed electronic health records database who had been treated for aRCC from November 1, 2009 to August 31, 2012. The patients received first-line therapy with pazopanib (cohort 1), followed by second-line therapy with either everolimus or temsirolimus (cohort 2). The key outcomes included overall survival (OS), PFS, adverse events (AEs), treatment patterns, and healthcare resource use., Results: The median OS in cohort 1 (n = 177) was 22 months, and the median PFS was 8.5 months. The most common AEs were fatigue (56%), diarrhea (52%), vomiting (44%), and nausea (40%). The median persistence was 151 days with pazopanib. The median OS in cohort 2 (n = 35) was 16 months; the median PFS was 5.7 months. The most common AEs were fatigue (51%) and nausea (34%). The median persistence was 93 days with everolimus and 49 days with temsirolimus., Conclusion: The outcomes for the patients treated with first-line pazopanib in the community setting were consistent with those reported by previous prospective and retrospective studies. Although the second-line cohort was small, the results of mTOR inhibitors after pazopanib were also consistent with those of previous observations., (Copyright © 2015 Elsevier Inc. All rights reserved.)

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.

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: Pazopanib is an oral tyrosine kinase inhibitor with demonstrated efficacy and tolerability in patients with advanced renal cell carcinoma (RCC)., Objective: To examine pazopanib persistence and compliance (adherence) and other drug utilization patterns in both treatment-naïve (first-line) patients and those previously treated with RCC therapy in the real-world setting. Key factors affecting persistence and compliance were also explored., Methods: This was a retrospective claims analysis using the Truven Health MarketScan Databases to cover claims activity from October 2007 through March 2012. Patients with advanced RCC aged ≥ 18 years who had received pazopanib with 180 days of follow-up were included. Bivariate comparisons of results from first-line and previously treated patients with RCC were conducted. Pazopanib persistence was measured using (a) estimated level of persistence with therapy (ELPT; i.e., the percentage of patients remaining on therapy at 30, 60, and 90 days [patients were censored at 180 days]); (b) time to discontinuation (i.e., duration of therapy); and (c) proportion of days covered (PDC; i.e., the ratio of [total days drug available minus days' supply of last prescription] to [last prescription date minus first prescription date]). Compliance was measured by medication possession ratio (MPR; i.e., the ratio of [total days' supply minus days' supply of last prescription] to [last prescription date minus first prescription date]). Other drug utilization measures included days' supply, time to initiation, time to switching, and dose-related measures. Random forest models were used to explore key factors of pazopanib persistence and compliance., Results: A total of 143 patients met all inclusion criteria; 43.3% were treated with pazopanib first line (first-line cohort), and 56.6% had ≥ 1 prior lines of therapy (previously treated cohort). The mean (± standard deviation [SD]) age of patients was 62.9 (± 10.3) years, and 71.3% of them were males. Continuous pazopanib therapy for up to 90 days was observed in greater than 50% of patients in both cohorts. In the first-line cohort, ELPT at 30, 60, and 90 days was 98.39%, 70.97%, and 56.45%, respectively; the mean (± SD) number of days to discontinuation was 112.2 (± 62.8); the mean (± SD) PDC was 84.7% (± 16.7%); and the mean (± SD) MPR was 85.2% (± 16.9%). Similar results were observed in the previously treated population: ELPT at 30, 60, and 90 days was 98.77%, 75.31%, and 58.02%, respectively; the mean (± SD) number of days to discontinuation was 118.7 (± 61.4); the mean (± SD) PDC was 87.8% (± 13.5%); and the mean (± SD) MPR was 90.1% (± 13.9%). Differences between the 2 cohorts were not statistically significant. More than 90% of patients in both cohorts had at least a 30-day supply of therapy (91.9% of first-line versus 90.2% of previously treated; P = 0.153). The mean (± SD) time from metastatic diagnosis to start of pazopanib therapy was 104.7 (± 199.3) days in the first-line cohort and 360.9 (± 187.0) days in previously treated patients (P = 0.001). Forty-six patients switched to another therapy: 17 patients in the first-line cohort and 29 patients in the previously treated cohort; the mean (± SD) time to switching therapy from each cohort was 94.7 (± 41.4) days and 87.8 (± 49.6) days (P = 0.146), respectively. Statistically significant differences were observed for the starting and ending doses between the 2 cohorts. The average daily dosage of pazopanib was greater than 700 mg in both cohorts (P = 0.055), with a maximum dose of 800 mg. Random forest models demonstrated that younger age and higher comorbidity predicted both higher persistence and compliance., Conclusions: In this observational study, greater than 50% of patients with advanced RCC were on pazopanib for almost 4 months, with the majority of both cohorts achieving high persistence and high compliance. Additionally, younger age and higher comorbidity index were the strongest predictors of both greater persistence and compliance. Further studies with larger cohorts and longer follow-up are needed to validate these findings.

Objective: To estimate the costs of adverse events (AEs) in patients aged ≥65 years with metastatic renal cell carcinoma (mRCC)., Methods: Retrospective study using the linked Surveillance, Epidemiology and End Results (SEER) Medicare database. Study subjects consisted of persons in SEER-Medicare, aged ≥65 years, with evidence of newly diagnosed mRCC between January 1, 2007 and December 31, 2007. Adverse events of interest consisted of Grade 3 or 4 toxicities that have been reported with frequency ≥5% in randomized controlled trials of sunitinib, sorafenib, bevacizumab, and pazopanib (i.e., targeted therapies for mRCC), and included abdominal pain, back pain, diarrhea, dyspnea, extremity pain, fatigue/asthenia, hand-foot syndrome, hypertension, lymphopenia, nausea/vomiting, neutropenia, proteinuria, and thrombocytopenia. Patients in SEER-Medicare with these events were identified based on ICD-9-CM diagnosis codes on Medicare claims. For each AE of interest, costs were tallied among evented patients over 30 days, beginning with the date of each patient's first mention of the AE, and were compared with those of non-evented patients over a similar 30-day period beginning with an identical 'shadow' index date. Total costs were compared on an unadjusted basis and with adjustment for differences in baseline characteristics using a generalized linear model., Results: A total of 881 patients with mRCC met study entry criteria; 60% of these patients had Medicare claims with mention of one or more AEs of interest. Events occurring with frequency >20% included abdominal pain, dyspnea, and fatigue/asthenia; 10-20% of study subjects had encounters for back pain, extremity pain, and nausea/vomiting. Mean (standard deviation) total cost of care over 30 days was substantially higher among patients with AEs ($13,944 [$14,529]) compared with those without mention of these events ($1878 [$5264]). Adjusting for differences in baseline characteristics, the mean (95% confidence interval) difference in costs between evented and non-evented patients was $12,410 ($9217-$16,522). Study limitations include problems in event ascertainment due to inaccuracies in ICD-9-CM coding on Medicare claims data, and restriction of the study population to patients with metastatic involvement at initial diagnosis of RCC., Conclusions: Costs of care are substantially higher in patients aged ≥65 years with mRCC who experience AEs commonly associated with sunitinib, sorafenib, bevacizumab, and pazopanib. Efforts to prevent and/or better manage these events potentially can reduce healthcare costs.

Background: Pazopanib and sunitinib provided a progression-free survival benefit, as compared with placebo or interferon, in previous phase 3 studies involving patients with metastatic renal-cell carcinoma. This phase 3, randomized trial compared the efficacy and safety of pazopanib and sunitinib as first-line therapy., Methods: We randomly assigned 1110 patients with clear-cell, metastatic renal-cell carcinoma, in a 1:1 ratio, to receive a continuous dose of pazopanib (800 mg once daily; 557 patients) or sunitinib in 6-week cycles (50 mg once daily for 4 weeks, followed by 2 weeks without treatment; 553 patients). The primary end point was progression-free survival as assessed by independent review, and the study was powered to show the noninferiority of pazopanib versus sunitinib. Secondary end points included overall survival, safety, and quality of life., Results: Pazopanib was noninferior to sunitinib with respect to progression-free survival (hazard ratio for progression of disease or death from any cause, 1.05; 95% confidence interval [CI], 0.90 to 1.22), meeting the predefined noninferiority margin (upper bound of the 95% confidence interval, <1.25). Overall survival was similar (hazard ratio for death with pazopanib, 0.91; 95% CI, 0.76 to 1.08). Patients treated with sunitinib, as compared with those treated with pazopanib, had a higher incidence of fatigue (63% vs. 55%), the hand-foot syndrome (50% vs. 29%), and thrombocytopenia (78% vs. 41%); patients treated with pazopanib had a higher incidence of increased levels of alanine aminotransferase (60%, vs. 43% with sunitinib). The mean change from baseline in 11 of 14 health-related quality-of-life domains, particularly those related to fatigue or soreness in the mouth, throat, hands, or feet, during the first 6 months of treatment favored pazopanib (P<0.05 for all 11 comparisons)., Conclusions: Pazopanib and sunitinib have similar efficacy, but the safety and quality-of-life profiles favor pazopanib. (Funded by GlaxoSmithKline Pharmaceuticals; COMPARZ ClinicalTrials.gov number, NCT00720941.).