Bisphosphonates in Patients with Renal Cell Carcinoma and Bone Metastases: A Sunitinib Global Expanded-Access Trial Subanalysis

Vrdoljak, Eduard; Gore, Martin; Leyman, Sophie; Szczylik, Cezary; Харкевич, Г. Ю.; Schöffski, Patrick; Torday, Laszlo; Mardiak, J; Zhang, Ke; Sajben, Peter; Sella, Avishay

doi:10.2217/fon.15.140

Cited by 8 publications

(9 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Given the fact that the IMDC risk score was worse in patients treated with concomitant BRIs, it is possible that concomitant administration of BRIs might have given a small advantage in outcome. This would be in coherence with the hypothesis of Vrdoljak et al [18] and with our own observations in m-ccRCC patients with BM [24].…”

Section: Discussionsupporting

confidence: 94%

“…More aggressive primary kidney tumors might have a higher spread to bones. Vrdoljak et al showed a worse performance status when BM were present [18]. We could not replicate this in our current analysis.…”

Section: Discussioncontrasting

confidence: 82%

“…An analysis by our own research group, including 223 m-ccRCC patients who started first-line sunitinib, showed a significantly worse mPFS (8.2 vs. 19.1 months; P < 0.0001) and mOS (19.5 vs. 38.5 months; P < 0.0001) [17]. Vrdoljak et al found a mPFS of 8.1 vs. 10.8 months (P = 0.007) and a mOS of 14.1 vs. 22.0 months (P < 0.001) in their cohort of 4410 mRCC patients (of which 88.4% were ccRCC) [18]. In a series including 1059 mRCC patients treated with sunitinib, a significantly worse mOS was observed in presence of BM (16.1 vs. 27.8 months, P < 0.0001).…”

Section: Discussionmentioning

confidence: 95%

See 2 more Smart Citations

Bone metastasis is associated with poor prognosis in metastatic papillary renal cell carcinoma patients treated with first agent angiogenesis inhibitors

Haaker

Tryssesoone

Renders

et al. 2020

Urologic Oncology: Seminars and Original Investigations

View full text Add to dashboard Cite

Objective: Papillary renal cell carcinoma (papRCC) is a rare (10%−15%) subtype of renal cancer. Few prognostic biomarkers have been described in metastatic papRCC (m-papRCC) patients treated with vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKIs). We aimed to study the prognostic impact of bone metastases (BM) on response rate, progression-free and overall survival (PFS and OS) in patients with m-papRCC treated with first agent VEGFR-TKIs. Patients and methods: A multicentric, retrospective analysis of patient records was conducted. BM were detected by computed tomography and/or bone scintigraphy. The International Metastatic RCC Database Consortium (IMDC) score was calculated at start of first agent VEGFR-TKI treatment. Results: Forty-nine patients were included. Best objective response was partial response in 20%, stable disease in 60% and early progressive disease in 20% of patients. Median PFS (mPFS) was 6.0 months and median OS (mOS) 14.0 months after start of first agent VEGFR-TKI. The IMDC score correlated with mOS: 77.5 months in good, 17.0 months in intermediate and 8.0 months in poor risk patients (P = 0.002). Patients with BM had a poorer outcome compared to patients without BM: mPFS was 4.0 vs. 7.0 months (P = 0.006) and mOS 7.5 vs. 19.0 months (P = 0.002). On bivariate analysis, the presence of BM was independently associated with PFS (P = 0.02) and OS (P = 0.049), independent of the IMDC risk groups. Benoit Beuselinck is senior clinical investigator of the Fonds voor Wetenschappelijk Onderzoek Vlaanderen (Belgium) grant (1801520N). Annelies Verbiest received a Fonds voor Wetenschappelijk Onderzoek Vlaanderen (Belgium) grant (1121619N). Eduard Roussel received an IPSEN research grant.

show abstract

Section: Discussionsupporting

confidence: 94%

Section: Discussioncontrasting

confidence: 82%

Section: Discussionmentioning

confidence: 95%

See 1 more Smart Citation

Bone metastasis is associated with poor prognosis in metastatic papillary renal cell carcinoma patients treated with first agent angiogenesis inhibitors

Haaker

Tryssesoone

Renders

et al. 2020

Urologic Oncology: Seminars and Original Investigations

View full text Add to dashboard Cite

show abstract

“…The prognostic significance of bone metastases has been established in multiple analyses of sunitinib and VEGF therapies [40,41]. For example, in a retrospective analysis of patients from the sunitinib expanded-access program with (n 5 1,147) versus without (n 5 2,817) baseline bone metastases who did not receive bisphosphonates, the median OS was 14.1 versus 22.0 months (HR, 0.7004; p < .0001; and HR, 0.841; p < .001 by univariate and multivariate analysis, respectively) [41]. The IMDC prognostic model was externally validated using the final patient data from the sunitinib expanded-access program-the largest contemporary patient population evaluated to date using an RCC prognostic model [28].…”

Section: Prognostic Factors and Patient Selection For Sunitinibmentioning

confidence: 99%

Sunitinib: Ten Years of Successful Clinical Use and Study in Advanced Renal Cell Carcinoma

Motzer

Escudier

Gannon³

et al. 2017

The Oncologist

View full text Add to dashboard Cite

The oral multikinase inhibitor sunitinib malate was approved by the U.S. Food and Drug Administration in January 2006 for use in patients with advanced renal cell carcinoma (RCC). Since then, it has been approved globally for this indication and for patients with imatinib-resistant or -intolerant gastrointestinal stromal tumors and advanced pancreatic neuroendocrine tumors. As we mark the 10-year anniversary of the beginning of the era of targeted therapy, and specifically the approval of sunitinib, it is worthwhile to highlight the progress that has been made in advanced RCC as it relates to the study of sunitinib. We present the key trials and data for sunitinib that established it as a reference standard of care for first-line advanced RCC therapy and, along with other targeted agents, significantly altered the treatment landscape in RCC. Moreover, we discuss the research with sunitinib that has sought to refine its role via patient selection and prognostic markers, improve dosing and adverse event management, and identify predictive efficacy biomarkers, plus the extent to which this research has contributed to the overall understanding and management of RCC. We also explore the key learnings regarding study design and data interpretation from the sunitinib studies and how these findings and the sunitinib development program, in general, can be a model for successful development of other agents. Finally, ongoing research into the continued and future role of sunitinib in RCC management is discussed. The Oncologist 2017;22:41-52 Implications for Practice: Approved globally, sunitinib is established as a standard of care for first-line advanced renal cell carcinoma (RCC) therapy and, along with other targeted agents, has significantly altered the treatment landscape in RCC. Research with sunitinib that has sought to refine its role via patient selection and prognostic markers, improve dosing and adverse event management, and identify predictive efficacy biomarkers has contributed to the overall understanding and management of RCC. Key learnings regarding study design and data interpretation from the sunitinib studies and the sunitinib development program, in general, can be a model for the successful development of other agents.

show abstract

“…Preventing the occurrence of BM in ccRCC patients would provide substantial clinical benefit. Bone resorption inhibitors such as bisphosphonates or denosumab can reduce the number of SRE, though their impact on outcome is not precisely defined [ 6 , 7 , 8 ]. In order to provide additional therapeutic options to limit the occurrence of BM in ccRCC, better understanding of the underlying molecular mechanisms is required.…”

Section: Introductionmentioning

confidence: 99%

MicroRNAs Possibly Involved in the Development of Bone Metastasis in Clear-Cell Renal Cell Carcinoma

Kinget

Roussel

Lambrechts

et al. 2021

Cancers

View full text Add to dashboard Cite

Bone metastasis in clear-cell renal cell carcinoma (ccRCC) leads to substantial morbidity through skeletal related adverse events and implicates worse clinical outcomes. MicroRNAs (miRNA) are small non-protein coding RNA molecules with important regulatory functions in cancer development and metastasis. In this retrospective analysis we present dysregulated miRNA in ccRCC, which are associated with bone metastasis. In particular, miR-23a-3p, miR-27a-3p, miR-20a-5p, and miR-335-3p specifically correlated with the earlier appearance of bone metastasis, compared to metastasis in other organs. In contrast, miR-30b-3p and miR-139-3p were correlated with less occurrence of bone metastasis. These miRNAs are potential biomarkers and attractive targets for miRNA inhibitors or mimics, which could lead to novel therapeutic possibilities for bone targeted treatment in metastatic ccRCC.

show abstract

Bisphosphonates in Patients with Renal Cell Carcinoma and Bone Metastases: A Sunitinib Global Expanded-Access Trial Subanalysis

Abstract: Bone metastases may have a negative prognostic impact in metastatic renal cell carcinoma. Bisphosphonates may have delayed early disease progression for prognostically worse sunitinib/bisphosphonate-treated patients.

Cited by 8 publications

References 19 publications

Bone metastasis is associated with poor prognosis in metastatic papillary renal cell carcinoma patients treated with first agent angiogenesis inhibitors

Bone metastasis is associated with poor prognosis in metastatic papillary renal cell carcinoma patients treated with first agent angiogenesis inhibitors

Sunitinib: Ten Years of Successful Clinical Use and Study in Advanced Renal Cell Carcinoma

MicroRNAs Possibly Involved in the Development of Bone Metastasis in Clear-Cell Renal Cell Carcinoma

Contact Info

Product

Resources

About