Dataset Information

Pazopanib has equivalent anti-tumor effectiveness and lower Total costs than Sunitinib for treating metastatic or advanced renal cell carcinoma: a meta-analysis.

ABSTRACT:

Background

Sunitinib and pazopanib are extensively used as first-line treatment of metastatic renal cell carcinoma (mRCC). We performed this meta-analysis to assess the anti-tumor effectiveness, toxicity, and total costs of the two drugs among patients with mRCC/advanced RCC (aRCC).

Materials and methods

PubMed, ScienceDirect, Scopus, Web of Science, Ovid MEDLINE, the Cochrane Library, Embase, and Google Scholar were searched to obtain eligible articles. The endpoints included progression-free survival (PFS), overall survival (OS), adverse effects (AEs), and per-patient-per-month (PPPM) costs.

Results

We included 14 medium- to high-quality studies. Both drugs were valid for mRCC/aRCC, with equivalent PFS (hazard ratio (HR) =1.06, 95% confidence interval [CI]: 0.98-1.15, P = 0.13), OS (HR = 0.92, 95% CI: 0.79-1.07, P = 0.29), objective response rate (ORR, risk ratio (RR) =1.03, 95% CI: 0.93-1.13, p = 0.58), and disease control rate (DCR, RR = 1.03, 95% CI: 0.94-1.22, P = 0.54). Sunitinib had more dosage reductions and higher PPPM (weighted mean difference = - 1.50 thousand US dollars, 95% CI: - 2.27 to - 0.72, P = 0.0002). Furthermore, more incidences of severe fatigue, thrombocytopenia, and neutropenia were recorded for sunitinib, but pazopanib had more liver toxicity. In subgroup analysis, studies from the US reported longer OS (HR = 0.86, 95% CI: 0.77-0.95, P = 0.004) and higher ORR (RR = 1.24, 95% CI: 1.03-1.51, P = 0.03).

Conclusions

Pazopanib provides equivalent anti-tumor effectiveness and lower PPPM as compared with sunitinib for mRCC/aRCC. Great care should be given to pazopanib-treated patients with abnormal liver function. Nevertheless, more large-scale, high-quality studies are required.

SUBMITTER: Deng H

PROVIDER: S-EPMC6533682 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Publications

Pazopanib has equivalent anti-tumor effectiveness and lower Total costs than Sunitinib for treating metastatic or advanced renal cell carcinoma: a meta-analysis.

Deng Huan H Huang Yu Y Hong Zhengdong Z Yuan Xuhui X Cao Zhi Z Wei Yiping Y Zhang Wenxiong W

BMC cancer 20190523 1

<h4>Background</h4>Sunitinib and pazopanib are extensively used as first-line treatment of metastatic renal cell carcinoma (mRCC). We performed this meta-analysis to assess the anti-tumor effectiveness, toxicity, and total costs of the two drugs among patients with mRCC/advanced RCC (aRCC).<h4>Materials and methods</h4>PubMed, ScienceDirect, Scopus, Web of Science, Ovid MEDLINE, the Cochrane Library, Embase, and Google Scholar were searched to obtain eligible articles. The endpoints included pro ...[more]

PMID: 31122210

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Project description:BackgroundPazopanib 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.ObjectivesTo (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.MethodsTotal 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.ResultsA 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.ConclusionsThe findings suggest that health care costs were lower among patients with advanced RCC treated first-line with pazopanib versus sunitinib.

Project description:BackgroundIn Canada and elsewhere, pazopanib and sunitinib-tyrosine kinase inhibitors targeting the vascular endothelial growth factor receptors-are recommended as first-line treatment for patients with metastatic renal cell carcinoma (mrcc). A large randomized noninferiority trial of pazopanib versus sunitinib (comparz) demonstrated that the two drugs have similar efficacy; however, patients randomized to pazopanib experienced better health-related quality of life (hrqol) and nominally lower rates of non-study medical resource utilization.MethodsThe cost-effectiveness of pazopanib compared with sunitinib for first-line treatment of mrcc from a Canadian health care system perspective was evaluated using a partitioned-survival model that incorporated data from comparz and other secondary sources. The time horizon of 5 years was based on the maximum duration of follow-up in the final analysis of overall survival from the comparz trial. Analyses were conducted first using list prices for pazopanib and sunitinib and then by assuming that the prices of sunitinib and pazopanib would be equivalent.ResultsBased on list prices, expected costs were CA$10,293 less with pazopanib than with sunitinib. Pazopanib was estimated to yield 0.059 more quality-adjusted life-years (qalys). Pazopanib was therefore dominant (more qalys and lower costs) compared with sunitinib in the base case. In probabilistic sensitivity analyses, pazopanib was dominant in 79% of simulations and was cost-effective in 90%-100% of simulations at a threshold cost-effectiveness ratio of CA$100,000. Assuming equivalent pricing, pazopanib yielded CA$917 in savings in the base case, was dominant in 36% of probabilistic sensitivity analysis simulations, and was cost-effective in 89% of simulations at a threshold cost-effectiveness ratio of CA$100,000.ConclusionsCompared with sunitinib, pazopanib is likely to be a cost-effective option for first-line treatment of mrcc from a Canadian health care perspective.

Project description:BackgroundSunitinib and pazopanib are the only two targeted therapies for the first-line treatment of locally advanced or metastatic renal cell carcinoma (mRCC) recommended by the United Kingdom's National Institute for Health and Care Excellence. Pazopanib demonstrated non-inferior efficacy and a differentiated safety profile versus sunitinib in the phase III COMPARZ trial. The current analysis provides a direct comparison of the cost-effectiveness of pazopanib versus sunitinib from the perspective of the United Kingdom's National Health Service based on data from COMPARZ and other sources.MethodsA partitioned-survival analysis model with three health states (alive with no progression, alive with progression, or dead) was used to estimate the incremental cost per quality-adjusted life-year (QALY) gained for pazopanib versus sunitinib over five years (duration of follow-up for final survival analysis in COMPARZ). The proportion of patients in each health state over time was based on Kaplan-Meier distributions for progression-free and overall survival from COMPARZ. Utility values were based on EQ-5D data from the pivotal study of pazopanib versus placebo. Costs were based on medical resource utilisation data from COMPARZ and unit costs from secondary sources. Probabilistic and deterministic sensitivity analyses were conducted to assess uncertainty of model results.ResultsIn the base case, pazopanib was estimated to provide more QALYs (0.0565, 95% credible interval [CrI]: -0.0920 to 0.2126) at a lower cost (-£1,061, 95% CrI: -£4,328 to £2,067) versus sunitinib. The probability that pazopanib yields more QALYs than sunitinib was estimated to be 76%. For a threshold value of £30,000 per QALY gained, the probability that pazopanib is cost-effective versus sunitinib was estimated to be 95%. Pazopanib was dominant in most scenarios examined in deterministic sensitivity analyses.ConclusionsPazopanib is likely to be a cost-effective treatment option compared with sunitinib as first-line treatment of mRCC in the United Kingdom.

Project description:BackgroundCombination treatment with immune checkpoint inhibitors and antiangiogenic drugs has shown encouraging preliminary antitumor activity across various tumor types including advanced or metastatic renal cell carcinoma (aRCC). The open-label, parallel-cohort, dose-escalation, phase I CheckMate 016 study evaluated the efficacy and safety of nivolumab in combination with antiangiogenic tyrosine kinase inhibitors or ipilimumab. Long-term outcomes from this study for the combination of nivolumab plus sunitinib or pazopanib in aRCC are presented.MethodsPatients with aRCC received nivolumab plus either sunitinib (50 mg/day, 4 weeks on/2 weeks off; N + S) or pazopanib (800 mg/day; N + P) until progression/unacceptable toxicity. The nivolumab starting dose was 2 mg/kg every 3 weeks, with planned escalation to 5 mg/kg every 3 weeks. Primary endpoints were safety and tolerability; antitumor activity was a secondary endpoint.ResultsArm N + S enrolled 33 patients, 19 of whom were treatment-naïve; this arm advanced to the expansion phase. Median follow-up was 50.0 months. Patients experienced high frequencies of adverse events (AEs) including treatment-related AEs (100%), grade 3/4 treatment-related AEs (82%), and treatment-related AEs leading to discontinuation (39%). Investigator-assessed objective response rate (ORR) was 55% (18/33) and median progression-free survival (PFS) was 12.7 months. Median overall survival (OS) was not reached. Arm N + P enrolled 20 patients, all had ≥1 prior systemic therapy; this arm was closed due to dose-limiting toxicities and did not proceed to expansion. Median follow-up was 27.1 months. Patients treated with N + P experienced high frequencies of AEs including treatment-related AEs (100%), grade 3/4 treatment-related AEs (70%), and treatment-related AEs leading to discontinuation (25%). Investigator-assessed ORR was 45% (9/20) and median PFS was 7.2 months. Median OS was 27.9 months.ConclusionsThe addition of standard doses of sunitinib or pazopanib to nivolumab resulted in a high incidence of high-grade toxicities limiting future development of either combination regimen. While there was no adverse impact on response and the OS outcome was notable, the findings suggest that the success of combination regimens based on immune checkpoint inhibitors and antiangiogenic drugs may be dependent on careful selection of the antiangiogenic component and dose.Trial registrationClinicaltrials.gov identifier: NCT01472081 . Registered 16 November 2011.

Dataset Information

Pazopanib has equivalent anti-tumor effectiveness and lower Total costs than Sunitinib for treating metastatic or advanced renal cell carcinoma: a meta-analysis.

Background

Materials and methods

Results

Conclusions

Publications

Pazopanib has equivalent anti-tumor effectiveness and lower Total costs than Sunitinib for treating metastatic or advanced renal cell carcinoma: a meta-analysis.

Similar Datasets

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