Outcomes of Patients With Metastatic Non–Clear-Cell Renal Cell Carcinoma Treated With Pazopanib

Matrana, Marc; Baiomy, Ali; Campbell, Matthew T.; Alamri, Suhail; Shetty, Akhil; Teegavarapu, Purnima Sravanti; Kalra, Sarathi; Xiao, Lianchun; Atkinson, Bradley J.; Corn, Paul G.; Jonasch, Eric; Elsayes, Khaled M.; Tannir, Nizar M.

doi:10.1016/j.clgc.2016.07.016

Cited by 27 publications

(38 citation statements)

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“…Looking at the different “real world” experiences, the mPFS was 8.5 months in the Vogelzang et al (2015) analysis, 13.7 months in the MD Anderson Cancer Center study 17 (Matrana et al, 2013a), and 13.0 months in the Christie study (Galvis et al, 2013), in which the 74% of the patients receiving PAZ was treatment-naïve. The variations in the mPFS observed in these studies could have resulted from varying operational definitions of PFS such as different timing and frequency of disease assessment.…”

Section: Discussionmentioning

confidence: 99%

Pazopanib in Metastatic Renal Cancer: A “Real-World” Experience at National Cancer Institute “Fondazione G. Pascale”

et al. 2016

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Pazopanib is an oral angiogenesis inhibitor, currently approved for treatment of metastatic renal cell carcinoma (mRCC) and soft tissue sarcoma. The present study analyzed the outcomes of pazopanib in first-line treatment of mRCC, in a single Italian cancer center. In the light of the retrospective, observational nature and the unselected population, our experience can be defined a “real-world” study. The medical records of 38 mRCC patients treated with front-line pazopanib were retrospectively reviewed and analyzed. The progression free survival (PFS) and the overall survival (OS) were the primary endpoints, while secondary objectives included objective response rate (ORR), disease control rate (DCR), and treatment tolerability. Pazopanib achieved a median PFS (mPFS) of 12.7 months (95% CI, 6.9–18.5 months). The median OS (mOS) was 26.2 months (95% CI, 12.6–39.9 months); the observed ORR and DCR were 30.3 and 72.7%, respectively, with a median duration of response of 11 weeks. mPFS appeared not to be influenced by number of co-morbidities (< 3 vs. ≥3), gender, Fuhrman grade and age. Conversely, the ORR and the DCR positively affect the mPFS (HR = 0.05 [95% CI, 0.05–0.55], p = 0.01; HR = 0.10 [95% CI, 0.02–0.43], p = 0.002, respectively). A worse outcome was associated with a lower mPFS in patients with liver metastases (p = 0.2) and with a high tumor burden (number of metastatic sites < 6 vs. ≥6) (p = 0.08). Worst OS was observed in patients aged ≥70 years old (HR = 6.91 [95% CI, 1.49–31.91], p = 0.01). The treatment was well-tolerated: no grade 4 adverse events, nor discontinuation due to toxicities was reported. Grade 3 hypertension affected positively the OS reaching the statistical significance (HR = 0.22 [95% CI, 0.05–0.8], p = 0.03). Thyroid dysfunction (hypo and hyperthyroidism) seems to correlate with better outcome in terms of a longer mPFS (HR = 0.12 [95% CI, 0.02–0.78], p = 0.02). Our results are consistent with those reported in prospective phase III trials and the published retrospective “real world” experiences. This analysis confirms the safety and efficacy of pazopanib in first-line setting, both in frail patients with multiple co-morbidities and Karnofsky PS < 80% and in younger, healthier patients with a number of metastatic sites < 6.

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Section: Discussionmentioning

confidence: 99%

Pazopanib in Metastatic Renal Cancer: A “Real-World” Experience at National Cancer Institute “Fondazione G. Pascale”

et al. 2016

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“…9 As for the CD RCC, CD-like minority areas have been known to be present in HLRCC-associated The diversity of RCC types in HLRCC patients must be emphasized. 24 Our series was too small to estimate outcomes associated with specific tyrosine kinase inhibitors in HLRCC. 11 The reality is more complex, and we hope that the broadening spectrum of RCC, as observed by us and recently by others, will be included in future classifications.…”

Section: Mutationsmentioning

confidence: 91%

Reassessing the clinical spectrum associated with hereditary leiomyomatosis and renal cell carcinoma syndrome in French FH mutation carriers

et al. 2017

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“…Дополнительные, хотя и ограниченные данные трех небольших исследований (проспективное исследова-ние II фазы [31], два ретроспективных исследования [32,33]), продемонстрировали эффективность пазопа-ниба у пациентов с метастатическим RCC несветлокле-точного гистологического варианта строения опухоли; еще одно проспективное исследование фазы II [34] продолжается. Кроме того, эффективность применения пазопаниба в первой линии у больных с метастатиче-ским ПКР любого гистологического подтипа также будет оценена в ходе продолжения проспективного исследования (PAZOREAL) [35].…”

Section: Discussionunclassified

Pazopanib as first-line therapy for patients with metastatic kidney cancer

Алексеев¹,

Shevchuk²

2018

Med. sov.

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Б.Я. АЛЕКСЕЕВ, д.м.н., профессор, И.М. ШЕВЧУК, к.м.н. Национальный медицинский исследовательский центр радиологии Минздрава России, Москва ПАЗОПАНИБ -ПРЕПАРАТ ПЕРВОЙ ЛИНИИ ТЕРАПИИ У БОЛЬНЫХ С МЕТАСТАТИЧЕСКИМ РАКОМ ПОЧКИ Пазопаниб (Вотриент®) -пероральный низкомолекулярный мультикиназный ингибитор, который в первую очередь инги-бирует рецептор 1, 2 и 3 сосудистого эндотелиального фактора роста, рецепторы α и β тромбоцитарного фактора роста эндотелия и рецепторы c-kit-фактора стволовых клеток. В предварительных экспериментах с использованием моделей ангиогенеза у мышей и кроликов пазопаниб ингибировал ангиогенез, вызванный комбинированным фактором роста эндо-телия сосудов и основным фактором роста фибробластов. Хотя препарат был разработан как терапевтический мультиопу-холевый агент, в настоящее время во многих странах он одобрен для применения при распространенной саркоме мягких тканей и почечно-клеточном раке (ПКР). В мультицентровых рандомизированных исследованиях по изучению эффектив-ности пазопаниба в качестве препарата первой линии у больных с метастатическим ПКР он продемонстрировал значитель-но лучшую безрецидивную выживаемость (БРВ) по сравнению с цитокиновой терапией и одинаковое время до прогресси-рования в случае применения сунитиниба. Кроме того, побочные эффекты, такие как нарушение функции печени и артери-альная гипертензия, как правило, управляемы, и с точки зрения качества жизни и экономической эффективности пазопаниб представляется более предпочтительным агентом по сравнению с другими альтернативными препаратами. Ключевые слова: метастатический почечно-клеточный рак, мультитаргетные ингибиторы тирозинкиназ, пазопаниб. B.Ya. ALEKSEEV, I.M. SHEVCHUK National Medical Research Radiological Center of the Ministry of Health of Russia, Moscow PAZOPANIB AS FIRST-LINE THERAPY FOR PATIENTS WITH METASTATIC KIDNEY CANCER Pazopanib (Votrient®) is an oral small-molecule multi-kinase inhibitor that predominantly inhibits vascular endothelial growthfactor receptor-1, -2 and -3, platelet-derived growth factor receptor-α and -β and the stem cell factor receptor c-Kit. In preliminary experiments using mouse and rabbit models of angiogenesis, pazopanib inhibited angiogenesis caused by a combined vascular endothelial growth factor and a major fibroblast growth factor. Although the drug was developed as a therapeutic multi-tumour agent, it is currently approved in many countries for the treatment of advanced soft tissue sarcoma and renal cell carcinoma (RCC). In multicentre, randomized trials of the efficacy of pazopanib as a first-line therapy in patients with metastatic RCC, progression-free survival (PFS) was significantly greater in pazopanib recipients than in cytokine recipients and pazopanib was noninferior to sunitinib with respect to time to disease progression. In addition, side effects such as liver dysfunction and hypertension can be usually managed, and pazopanib is likely to be a more preferred cost-effective option and shows better quality-of-life compared to other alternative drugs.

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Outcomes of Patients With Metastatic Non–Clear-Cell Renal Cell Carcinoma Treated With Pazopanib

Cited by 27 publications

References 4 publications

Pazopanib in Metastatic Renal Cancer: A “Real-World” Experience at National Cancer Institute “Fondazione G. Pascale”

Pazopanib in Metastatic Renal Cancer: A “Real-World” Experience at National Cancer Institute “Fondazione G. Pascale”

Reassessing the clinical spectrum associated with hereditary leiomyomatosis and renal cell carcinoma syndrome in French FH mutation carriers

Pazopanib as first-line therapy for patients with metastatic kidney cancer

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