Pazopanib versus Sunitinib in Metastatic Renal-Cell Carcinoma

Motzer, Robert J.; Hutson, Thomas E.; Cella, David; Reeves, James A.; Hawkins, Robert E.; Guo, Jun; Nathan, Paul; Staehler, Michael; Souza, Paul de; Merchan, Jaime R.; Boleti, Ekaterini; Fife, Kate; Jin, Jie; Jones, Robert J.; Uemura, Hirotsugu; Giorgi, Ugo De; Harmenberg, Ulrika; Wang, Jinwan; Sternberg, Cora N.; Deen, Keith C.; McCann, Lauren; Hackshaw, Michelle D.; Crescenzo, Rocco J.; Pandite, Lini; Choueiri, Toni K.

doi:10.1056/nejmoa1303989

Cited by 1,708 publications

(1,431 citation statements)

References 20 publications

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“…The aim was to induce stability of disease prior to nephrectomy in over 75% of patients, avoiding potential progression and clinical deterioration during the preoperative surgical period. The PFS and OS results [7.1 months and 22.7 months respectively] were acceptable and in line with those seen for similar risk groups in the pivotal randomized VEGF targeted therapy trials in which the majority of patients previously had nephrectomy [10][11][12] . Survival analysis showed that the prognostic factors in this specific group of patients are similar to those in unselected patients.…”

Section: Discussionsupporting

confidence: 74%

“…Both drugs have clinical benefit rates above 70% in this setting although the sunitinib trials focused mainly on safety rather than efficacy. Previous non-inferiority studies show these agents are non-inferior in terms of efficacy with differing adverse event profiles 11 . Our results support these findings.…”

Section: Discussionmentioning

confidence: 99%

“…However the approach achieves rapid control of disease in the majority of patients and is associated acceptable outcomes. Pazopanib appears an attractive agent in this setting due to its positive adverse event profile 11 . Our results question the role of CN in MSKCC poor risk disease in a single prospective study for the first time.…”

Section: Discussionmentioning

confidence: 99%

“…The median duration of therapy prior to surgery was 13 weeks (range [11][12][13][14]. The median size of the primary tumour before and after pazopanib was 10.…”

Section: Efficacy Of Upfront Pazopanibmentioning

confidence: 99%

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Safety and Efficacy of Pazopanib Therapy Prior to Planned Nephrectomy in Metastatic Clear Cell Renal Cancer

et al. 2016

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Section: Discussionsupporting

confidence: 74%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

“…The median duration of therapy prior to surgery was 13 weeks (range [11][12][13][14]. The median size of the primary tumour before and after pazopanib was 10.…”

Section: Efficacy Of Upfront Pazopanibmentioning

confidence: 99%

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Safety and Efficacy of Pazopanib Therapy Prior to Planned Nephrectomy in Metastatic Clear Cell Renal Cancer

et al. 2016

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“…HRQoL was assessed with the functional assessment of chronic illness therapy-fatigue (FACIT-F) questionnaire, the National Comprehensive Cancer Network/functional assessment of cancer therapy-kidney symptom index 19 (NCCN-FACT FKSI-19), and the cancer therapy satisfaction questionnaire. The study was open label50 …”

Section: Resultsmentioning

confidence: 99%

Availability of evidence of benefits on overall survival and quality of life of cancer drugs approved by European Medicines Agency: retrospective cohort study of drug approvals 2009-13

Davis

Naci

Gurpinar

et al. 2017

BMJ

487

415

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Objective To determine the availability of data on overall survival and quality of life benefits of cancer drugs approved in Europe. Design Retrospective cohort study. Setting Publicly accessible regulatory and scientific reports on cancer approvals by the European Medicines Agency (EMA) from 2009 to 2013. Main outcome measures Pivotal and postmarketing trials of cancer drugs according to their design features (randomisation, crossover, blinding), comparators, and endpoints. Availability and magnitude of benefit on overall survival or quality of life determined at time of approval and after market entry. Validated European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS) used to assess the clinical value of the reported gains in published studies of cancer drugs. Results From 2009 to 2013, the EMA approved the use of 48 cancer drugs for 68 indications. Of these, eight indications (12%) were approved on the basis of a single arm study. At the time of market approval, there was significant prolongation of survival in 24 of the 68 (35%). The magnitude of the benefit on overall survival ranged from 1.0 to 5.8 months (median 2.7 months). At the time of market approval, there was an improvement in quality of life in seven of 68 indications (10%). Out of 44 indications for which there was no evidence of a survival gain at the time of market authorisation, in the subsequent postmarketing period there was evidence for extension of life in three (7%) and reported benefit on quality of life in five (11%). Of the 68 cancer indications with EMA approval, and with a median of 5.4 years’ follow-up (minimum 3.3 years, maximum 8.1 years), only 35 (51%) had shown a significant improvement in survival or quality of life, while 33 (49%) remained uncertain. Of 23 indications associated with a survival benefit that could be scored with the ESMO-MCBS tool, the benefit was judged to be clinically meaningful in less than half (11/23, 48%). Conclusions This systematic evaluation of oncology approvals by the EMA in 2009-13 shows that most drugs entered the market without evidence of benefit on survival or quality of life. At a minimum of 3.3 years after market entry, there was still no conclusive evidence that these drugs either extended or improved life for most cancer indications. When there were survival gains over existing treatment options or placebo, they were often marginal.

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Comparative Survival Associated With Use of Targeted vs Nontargeted Therapy in Medicare Patients With Metastatic Renal Cell Carcinoma

Jahnke

Pettit

et al. 2019

JAMA Netw Open

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IMPORTANCE Targeted therapies for advanced renal cell carcinoma (RCC) have shown increased tolerability and survival advantages over older treatments in clinical trials, but understanding of realworld survival improvements is still emerging. OBJECTIVE To compare overall and RCC-specific survival associated with use of targeted vs nontargeted therapy for metastatic RCC. DESIGN, SETTING, AND PARTICIPANTS This retrospective cohort study used Surveillance, Epidemiology, and End Results-Medicare data from 2000 to 2013 to examine patients with stage IV (distant) clear cell RCC at the time of diagnosis who received any targeted or nontargeted therapy. A 2-stage residual inclusion model was fitted to estimate the survival advantages of targeted treatments using an instrumental variable approach to account for both measured and unmeasured group differences. Data analyses were conducted from July 24, 2017, to April 4, 2019. EXPOSURES Targeted therapy (study group) or nontargeted therapy (control group). MAIN OUTCOMES AND MEASURES Overall survival and RCC-specific survival, defined as the interval between the date of first drug treatment and date of death or end of the observation period. RESULTS The final sample included 1015 patients (mean [SD] age, 71.2 [8.1] years; 392 [39%] women); 374 (37%) received nontargeted therapy and 641 (63%) received targeted therapy. The targeted therapy group had a greater percentage of disabled patients (ie, those <65 years old who were eligible for Medicare because of disability) and older patients (ie, those Ն75 years old) and higher comorbidity index and disability scores compared with the nontargeted therapy group. Unadjusted Kaplan-Meier survival curves showed higher overall survival for targeted vs nontargeted therapy (log-rank test, χ 2 1 = 5.79; P = .02); median survival was not statistically significantly different (8.7 months [95% CI, 7.3-10.2 months] vs 7.2 months [95% CI, 5.8-8.8 months]; P = .14). According to the instrumental variable analysis, the median overall survival advantage was 3.0 months (95% CI, 0.7-5.3 months), and overall survival improvements associated with targeted therapy vs nontargeted therapy were statistically significant: 8% at 1 year (44% [95% CI, 39%-50%] vs 36% [95% CI, 30%-42%]; P = .01), 7% at 2 years (25% [95% CI, 20%-30%] vs 18% [95% CI, 13%-23%]; P = .009), and 5% at 3 years (15% [95% CI, 11%-19%] vs 10% [95% CI, 6%-13%]; P = .01). Receipt of targeted therapy was associated with a lower hazard of death compared with nontargeted therapy (overall survival hazard ratio, 0.78 [95% CI, 0.65-0.94]; RCC-specific survival hazard ratio, 0.77 [95% CI, 0.62-0.96]).

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Pazopanib versus Sunitinib in Metastatic Renal-Cell Carcinoma

Abstract: 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.).

Cited by 1,708 publications

References 20 publications

Safety and Efficacy of Pazopanib Therapy Prior to Planned Nephrectomy in Metastatic Clear Cell Renal Cancer

Safety and Efficacy of Pazopanib Therapy Prior to Planned Nephrectomy in Metastatic Clear Cell Renal Cancer

Availability of evidence of benefits on overall survival and quality of life of cancer drugs approved by European Medicines Agency: retrospective cohort study of drug approvals 2009-13

Comparative Survival Associated With Use of Targeted vs Nontargeted Therapy in Medicare Patients With Metastatic Renal Cell Carcinoma

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