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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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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: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.

Project description: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.

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.

Publications

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

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