Bisphosphonates combined with sunitinib may improve the response rate, progression free survival and overall survival of patients with bone metastases from renal cell carcinoma

Daniel Keizman, Maya Ish-Shalom, Roberto Pili, Hans Hammers, Mario A. Eisenberger, Victoria Sinibaldi, Ben Boursi, Natalie Maimon, Maya Gottfried, Henry Hayat, Avivit Peer, Svetlana Kovel, Avishay Sella, Raanan Berger, Michael A. Carducci

Research output: Contribution to journalArticle

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Abstract

Background: Bisphosphonates are used to prevent skeletal events of bone metastases, and may exhibit antitumour effects. We aimed to evaluate whether bisphosphonates can bring a response rate (RR), progression free survival (PFS) and overall survival (OS) benefit to patients with bone metastasis from renal cell carcinoma (RCC) that is treated with sunitinib. Methods: We performed a multicentre retrospective study of patients with bone metastases from RCC that was treated with sunitinib. The effect of bisphosphonates on RR, PFS and OS was tested with adjustment for known prognostic factors using a chi-square test from contingency table and partial likelihood test from Cox regression model. Results: Between 2004 and 2011, 209 patients with metastatic RCC were treated with sunitinib, 76 had bone metastases, 35 bisphosphonates users and 41 non-users. The groups of bisphosphonates users and non-users were balanced regarding known prognostic factors. Objective response was partial response/stable disease 86% (n = 30) versus 71% (n = 29), and progressive disease 14% (n = 5) versus 29% (n = 12) (p = 0.125, OR 2.48) in users versus non-users, respectively. Median PFS was 15 versus 5 months (HR = 0.55, p < 0.0001), and median OS was not reached (with a median follow-up time of 45 months) versus 14 months (HR = 0.4, p = 0.029), in favour of users. In multivariate analysis of the entire patient cohort (n = 76), factors associated with PFS were bisphosphonates use (HR = 0.58, p = 0.035), and pre-treatment neutrophil to lymphocyte ratio >3 (HR = 3.5, p = 0.009). Factors associated with OS were bisphosphonates use (HR = 0.5, p = 0.008), elevated pre-treatment alkaline phosphatase (HR = 2.9, p = 0.003) and sunitinib induced HTN (HR = 0.63, p < 0.0001). Conclusions: Bisphosphonates may improve the RR, PFS and OS of sunitinib treatment in RCC with bone metastases.

Original languageEnglish (US)
Pages (from-to)1031-1037
Number of pages7
JournalEuropean Journal of Cancer
Volume48
Issue number7
DOIs
StatePublished - May 2012
Externally publishedYes

Fingerprint

Diphosphonates
Renal Cell Carcinoma
Disease-Free Survival
Neoplasm Metastasis
Bone and Bones
Survival
Chi-Square Distribution
sunitinib
Proportional Hazards Models
Multicenter Studies
Alkaline Phosphatase
Retrospective Studies
Therapeutics

Keywords

  • Bisphosphonates
  • Bone metastases
  • Outcome
  • Renal cell carcinoma
  • Sunitinib

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Bisphosphonates combined with sunitinib may improve the response rate, progression free survival and overall survival of patients with bone metastases from renal cell carcinoma. / Keizman, Daniel; Ish-Shalom, Maya; Pili, Roberto; Hammers, Hans; Eisenberger, Mario A.; Sinibaldi, Victoria; Boursi, Ben; Maimon, Natalie; Gottfried, Maya; Hayat, Henry; Peer, Avivit; Kovel, Svetlana; Sella, Avishay; Berger, Raanan; Carducci, Michael A.

In: European Journal of Cancer, Vol. 48, No. 7, 05.2012, p. 1031-1037.

Research output: Contribution to journalArticle

Keizman, D, Ish-Shalom, M, Pili, R, Hammers, H, Eisenberger, MA, Sinibaldi, V, Boursi, B, Maimon, N, Gottfried, M, Hayat, H, Peer, A, Kovel, S, Sella, A, Berger, R & Carducci, MA 2012, 'Bisphosphonates combined with sunitinib may improve the response rate, progression free survival and overall survival of patients with bone metastases from renal cell carcinoma', European Journal of Cancer, vol. 48, no. 7, pp. 1031-1037. https://doi.org/10.1016/j.ejca.2012.02.050
Keizman, Daniel ; Ish-Shalom, Maya ; Pili, Roberto ; Hammers, Hans ; Eisenberger, Mario A. ; Sinibaldi, Victoria ; Boursi, Ben ; Maimon, Natalie ; Gottfried, Maya ; Hayat, Henry ; Peer, Avivit ; Kovel, Svetlana ; Sella, Avishay ; Berger, Raanan ; Carducci, Michael A. / Bisphosphonates combined with sunitinib may improve the response rate, progression free survival and overall survival of patients with bone metastases from renal cell carcinoma. In: European Journal of Cancer. 2012 ; Vol. 48, No. 7. pp. 1031-1037.
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abstract = "Background: Bisphosphonates are used to prevent skeletal events of bone metastases, and may exhibit antitumour effects. We aimed to evaluate whether bisphosphonates can bring a response rate (RR), progression free survival (PFS) and overall survival (OS) benefit to patients with bone metastasis from renal cell carcinoma (RCC) that is treated with sunitinib. Methods: We performed a multicentre retrospective study of patients with bone metastases from RCC that was treated with sunitinib. The effect of bisphosphonates on RR, PFS and OS was tested with adjustment for known prognostic factors using a chi-square test from contingency table and partial likelihood test from Cox regression model. Results: Between 2004 and 2011, 209 patients with metastatic RCC were treated with sunitinib, 76 had bone metastases, 35 bisphosphonates users and 41 non-users. The groups of bisphosphonates users and non-users were balanced regarding known prognostic factors. Objective response was partial response/stable disease 86{\%} (n = 30) versus 71{\%} (n = 29), and progressive disease 14{\%} (n = 5) versus 29{\%} (n = 12) (p = 0.125, OR 2.48) in users versus non-users, respectively. Median PFS was 15 versus 5 months (HR = 0.55, p < 0.0001), and median OS was not reached (with a median follow-up time of 45 months) versus 14 months (HR = 0.4, p = 0.029), in favour of users. In multivariate analysis of the entire patient cohort (n = 76), factors associated with PFS were bisphosphonates use (HR = 0.58, p = 0.035), and pre-treatment neutrophil to lymphocyte ratio >3 (HR = 3.5, p = 0.009). Factors associated with OS were bisphosphonates use (HR = 0.5, p = 0.008), elevated pre-treatment alkaline phosphatase (HR = 2.9, p = 0.003) and sunitinib induced HTN (HR = 0.63, p < 0.0001). Conclusions: Bisphosphonates may improve the RR, PFS and OS of sunitinib treatment in RCC with bone metastases.",
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T1 - Bisphosphonates combined with sunitinib may improve the response rate, progression free survival and overall survival of patients with bone metastases from renal cell carcinoma

AU - Keizman, Daniel

AU - Ish-Shalom, Maya

AU - Pili, Roberto

AU - Hammers, Hans

AU - Eisenberger, Mario A.

AU - Sinibaldi, Victoria

AU - Boursi, Ben

AU - Maimon, Natalie

AU - Gottfried, Maya

AU - Hayat, Henry

AU - Peer, Avivit

AU - Kovel, Svetlana

AU - Sella, Avishay

AU - Berger, Raanan

AU - Carducci, Michael A.

PY - 2012/5

Y1 - 2012/5

N2 - Background: Bisphosphonates are used to prevent skeletal events of bone metastases, and may exhibit antitumour effects. We aimed to evaluate whether bisphosphonates can bring a response rate (RR), progression free survival (PFS) and overall survival (OS) benefit to patients with bone metastasis from renal cell carcinoma (RCC) that is treated with sunitinib. Methods: We performed a multicentre retrospective study of patients with bone metastases from RCC that was treated with sunitinib. The effect of bisphosphonates on RR, PFS and OS was tested with adjustment for known prognostic factors using a chi-square test from contingency table and partial likelihood test from Cox regression model. Results: Between 2004 and 2011, 209 patients with metastatic RCC were treated with sunitinib, 76 had bone metastases, 35 bisphosphonates users and 41 non-users. The groups of bisphosphonates users and non-users were balanced regarding known prognostic factors. Objective response was partial response/stable disease 86% (n = 30) versus 71% (n = 29), and progressive disease 14% (n = 5) versus 29% (n = 12) (p = 0.125, OR 2.48) in users versus non-users, respectively. Median PFS was 15 versus 5 months (HR = 0.55, p < 0.0001), and median OS was not reached (with a median follow-up time of 45 months) versus 14 months (HR = 0.4, p = 0.029), in favour of users. In multivariate analysis of the entire patient cohort (n = 76), factors associated with PFS were bisphosphonates use (HR = 0.58, p = 0.035), and pre-treatment neutrophil to lymphocyte ratio >3 (HR = 3.5, p = 0.009). Factors associated with OS were bisphosphonates use (HR = 0.5, p = 0.008), elevated pre-treatment alkaline phosphatase (HR = 2.9, p = 0.003) and sunitinib induced HTN (HR = 0.63, p < 0.0001). Conclusions: Bisphosphonates may improve the RR, PFS and OS of sunitinib treatment in RCC with bone metastases.

AB - Background: Bisphosphonates are used to prevent skeletal events of bone metastases, and may exhibit antitumour effects. We aimed to evaluate whether bisphosphonates can bring a response rate (RR), progression free survival (PFS) and overall survival (OS) benefit to patients with bone metastasis from renal cell carcinoma (RCC) that is treated with sunitinib. Methods: We performed a multicentre retrospective study of patients with bone metastases from RCC that was treated with sunitinib. The effect of bisphosphonates on RR, PFS and OS was tested with adjustment for known prognostic factors using a chi-square test from contingency table and partial likelihood test from Cox regression model. Results: Between 2004 and 2011, 209 patients with metastatic RCC were treated with sunitinib, 76 had bone metastases, 35 bisphosphonates users and 41 non-users. The groups of bisphosphonates users and non-users were balanced regarding known prognostic factors. Objective response was partial response/stable disease 86% (n = 30) versus 71% (n = 29), and progressive disease 14% (n = 5) versus 29% (n = 12) (p = 0.125, OR 2.48) in users versus non-users, respectively. Median PFS was 15 versus 5 months (HR = 0.55, p < 0.0001), and median OS was not reached (with a median follow-up time of 45 months) versus 14 months (HR = 0.4, p = 0.029), in favour of users. In multivariate analysis of the entire patient cohort (n = 76), factors associated with PFS were bisphosphonates use (HR = 0.58, p = 0.035), and pre-treatment neutrophil to lymphocyte ratio >3 (HR = 3.5, p = 0.009). Factors associated with OS were bisphosphonates use (HR = 0.5, p = 0.008), elevated pre-treatment alkaline phosphatase (HR = 2.9, p = 0.003) and sunitinib induced HTN (HR = 0.63, p < 0.0001). Conclusions: Bisphosphonates may improve the RR, PFS and OS of sunitinib treatment in RCC with bone metastases.

KW - Bisphosphonates

KW - Bone metastases

KW - Outcome

KW - Renal cell carcinoma

KW - Sunitinib

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