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Published in: Targeted Oncology 2/2016

01-04-2016 | Original Research Article

Early Tumor Shrinkage Under Treatment with First-line Tyrosine Kinase Inhibitors as a Predictor of Overall Survival in Patients with Metastatic Renal Cell Carcinoma: a Retrospective Multi-Institutional Study in Japan

Authors: Hideaki Miyake, Akira Miyazaki, Satoshi Imai, Ken-ichi Harada, Masato Fujisawa

Published in: Targeted Oncology | Issue 2/2016

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Abstract

Background

Prognostic significance of early tumor shrinkage following treatment with tyrosine kinase inhibitors (TKIs) in patients with metastatic renal cell carcinoma (mRCC) has not been fully elucidated.

Objective

The aim of this study was to assess the impact of early tumor shrinkage induced by first-line TKIs on overall survival (OS) in mRCC patients.

Patients and Methods

This study retrospectively included 185 consecutive Japanese patients with mRCC treated with either sunitinib or sorafenib for at least 3 months as first-line molecular-targeted therapy between April 2011 and December 2014 at Kobe University Hospital and its affiliated institutions.

Results

Median OS in the 185 patients was 33.6 months. At 12 weeks after the introduction of TKIs, 9 patients had achieved tumor shrinkage from −100 to −50 %, 43 from −49 to −25 %, 61 from −24 to 0 %, and the remaining 72 patients showed an increase in tumor size. The median OS stratified according to tumor shrinkage as shown above was 59.2, 39.1, 31.4, and 16.1 months, respectively. Univariate analysis identified prior nephrectomy, Memorial Sloan Kettering Cancer Center (MSKCC) risk classification, C-reactive protein (CRP) level, liver metastasis, number of metastatic organs, histological subtype, sarcomatoid feature, and early tumor shrinkage as significant predictors of OS. Of these significant factors, only the MSKCC classification, CRP level, liver metastasis, and early tumor shrinkage were shown to be independently associated with OS on multivariate analysis.

Conclusions

Early tumor shrinkage could be a useful predictor of OS in mRCC patients receiving TKIs as a first-line molecular-targeted agent.
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Literature
1.
go back to reference Figlin R, Sternberg C, Wood CG (2012) Novel agents and approaches for advanced renal cell carcinoma. J Urol 188:707–715CrossRefPubMed Figlin R, Sternberg C, Wood CG (2012) Novel agents and approaches for advanced renal cell carcinoma. J Urol 188:707–715CrossRefPubMed
2.
go back to reference Motzer RJ, Hutson TE, Tomczak P et al (2007) Sunitinib versus interferon alfa in metastatic renal-cell carcinoma. N Engl J Med 356:115–124CrossRefPubMed Motzer RJ, Hutson TE, Tomczak P et al (2007) Sunitinib versus interferon alfa in metastatic renal-cell carcinoma. N Engl J Med 356:115–124CrossRefPubMed
3.
go back to reference Escudier B, Eisen T, Stadler WM et al (2007) Sorafenib in advanced clear-cell renal-cell carcinoma. N Engl J Med 356:125–134CrossRefPubMed Escudier B, Eisen T, Stadler WM et al (2007) Sorafenib in advanced clear-cell renal-cell carcinoma. N Engl J Med 356:125–134CrossRefPubMed
4.
go back to reference Motzer RJ, Hutson TE, Cella D et al (2013) Pazopanib versus sunitinib in metastatic renal-cell carcinoma. N Engl J Med 369:722–731CrossRefPubMed Motzer RJ, Hutson TE, Cella D et al (2013) Pazopanib versus sunitinib in metastatic renal-cell carcinoma. N Engl J Med 369:722–731CrossRefPubMed
5.
go back to reference Patard JJ, Pignot G, Escudier B et al (2011) ICUD-EAU International Consultation on Kidney Cancer 2010: treatment of metastatic disease. Eur Urol 60:684–690CrossRefPubMed Patard JJ, Pignot G, Escudier B et al (2011) ICUD-EAU International Consultation on Kidney Cancer 2010: treatment of metastatic disease. Eur Urol 60:684–690CrossRefPubMed
6.
go back to reference Gore ME, Szczylik C, Porta C et al (2009) Safety and efficacy of sunitinib for metastatic renal-cell carcinoma: an expanded-access trial. Lancet Oncol 10:757–763CrossRefPubMed Gore ME, Szczylik C, Porta C et al (2009) Safety and efficacy of sunitinib for metastatic renal-cell carcinoma: an expanded-access trial. Lancet Oncol 10:757–763CrossRefPubMed
7.
go back to reference Harshman LC, Xie W, Bjarnason GA et al (2012) Conditional survival of patients with metastatic renal-cell carcinoma treated with VEGF-targeted therapy: a population-based study. Lancet Oncol 13:927–935CrossRefPubMed Harshman LC, Xie W, Bjarnason GA et al (2012) Conditional survival of patients with metastatic renal-cell carcinoma treated with VEGF-targeted therapy: a population-based study. Lancet Oncol 13:927–935CrossRefPubMed
8.
go back to reference Miyake H, Miyazaki A, Harada K et al (2014) Assessment of efficacy, safety and quality of life of 110 patients treated with sunitinib as first-line therapy for metastatic renal cell carcinoma: experience in real-world clinical practice in Japan. Med Oncol 31:978CrossRefPubMed Miyake H, Miyazaki A, Harada K et al (2014) Assessment of efficacy, safety and quality of life of 110 patients treated with sunitinib as first-line therapy for metastatic renal cell carcinoma: experience in real-world clinical practice in Japan. Med Oncol 31:978CrossRefPubMed
9.
go back to reference Motzer RJ, Bacik J, Murphy BA et al (2002) Interferon-alfa as a comparative treatment for clinical trials of new therapies against advanced renal cell carcinoma. J Clin Oncol 20:289–296CrossRefPubMed Motzer RJ, Bacik J, Murphy BA et al (2002) Interferon-alfa as a comparative treatment for clinical trials of new therapies against advanced renal cell carcinoma. J Clin Oncol 20:289–296CrossRefPubMed
10.
go back to reference Heng DY, Xie W, Regan MM et al (2009) Prognostic factors for overall survival in patients with metastatic renal cell carcinoma treated with vascular endothelial growth factor-targeted agents: results from a large, multicenter study. J Clin Oncol 27:5794–5799CrossRefPubMed Heng DY, Xie W, Regan MM et al (2009) Prognostic factors for overall survival in patients with metastatic renal cell carcinoma treated with vascular endothelial growth factor-targeted agents: results from a large, multicenter study. J Clin Oncol 27:5794–5799CrossRefPubMed
11.
go back to reference Seidel C, Busch J, Weikert S et al (2012) Progression free survival of first line vascular endothelial growth factor-targeted therapy is an important prognostic parameter in patients with metastatic renal cell carcinoma. Eur J Cancer 48:1023–1030CrossRefPubMed Seidel C, Busch J, Weikert S et al (2012) Progression free survival of first line vascular endothelial growth factor-targeted therapy is an important prognostic parameter in patients with metastatic renal cell carcinoma. Eur J Cancer 48:1023–1030CrossRefPubMed
12.
go back to reference Seidel C, Busch J, Weikert S et al (2013) Tumour shrinkage measured with first treatment evaluation under VEGF-targeted therapy as prognostic marker in metastatic renal cell carcinoma (mRCC). Br J Cancer 109:2998–3004CrossRefPubMedPubMedCentral Seidel C, Busch J, Weikert S et al (2013) Tumour shrinkage measured with first treatment evaluation under VEGF-targeted therapy as prognostic marker in metastatic renal cell carcinoma (mRCC). Br J Cancer 109:2998–3004CrossRefPubMedPubMedCentral
13.
go back to reference Busch J, Seidel C, Goranova I et al (2014) Categories of response to first line vascular endothelial growth factor receptor targeted therapy and overall survival in patients with metastatic renal cell carcinoma. Eur J Cancer 50:563–569CrossRefPubMed Busch J, Seidel C, Goranova I et al (2014) Categories of response to first line vascular endothelial growth factor receptor targeted therapy and overall survival in patients with metastatic renal cell carcinoma. Eur J Cancer 50:563–569CrossRefPubMed
14.
go back to reference Krajewski KM, Franchetti Y, Nishino M et al (2014) 10% Tumor diameter shrinkage on the first follow-up computed tomography predicts clinical outcome in patients with advanced renal cell carcinoma treated with angiogenesis inhibitors: a follow-up validation study. Oncologist 19:507–514CrossRefPubMedPubMedCentral Krajewski KM, Franchetti Y, Nishino M et al (2014) 10% Tumor diameter shrinkage on the first follow-up computed tomography predicts clinical outcome in patients with advanced renal cell carcinoma treated with angiogenesis inhibitors: a follow-up validation study. Oncologist 19:507–514CrossRefPubMedPubMedCentral
15.
go back to reference Halabi S, Rini B, Escudier B, Stadler WM, Small EJ (2014) Progression-free survival as a surrogate endpoint of overall survival in patients with metastatic renal cell carcinoma. Cancer 120:52–60CrossRefPubMed Halabi S, Rini B, Escudier B, Stadler WM, Small EJ (2014) Progression-free survival as a surrogate endpoint of overall survival in patients with metastatic renal cell carcinoma. Cancer 120:52–60CrossRefPubMed
16.
go back to reference Grünwald V, McKay RR, Krajewski KM et al (2015) Depth of remission is a prognostic factor for survival in patients with metastatic renal cell carcinoma. Eur Urol 67:952–958CrossRefPubMedPubMedCentral Grünwald V, McKay RR, Krajewski KM et al (2015) Depth of remission is a prognostic factor for survival in patients with metastatic renal cell carcinoma. Eur Urol 67:952–958CrossRefPubMedPubMedCentral
17.
go back to reference Miyazaki A, Miyake H, Harada K, Inoue T, Fujisawa M (2015) Prognostic outcome in patients treated with tyrosine kinase inhibitors as first-line molecular-targeted therapy for metastatic renal cell carcinoma: experience in real-world clinical practice in Japan. Mol Clin Oncol 3:601–606PubMedPubMedCentral Miyazaki A, Miyake H, Harada K, Inoue T, Fujisawa M (2015) Prognostic outcome in patients treated with tyrosine kinase inhibitors as first-line molecular-targeted therapy for metastatic renal cell carcinoma: experience in real-world clinical practice in Japan. Mol Clin Oncol 3:601–606PubMedPubMedCentral
18.
go back to reference Eisenhauer EA, Therasse P, Bogaerts J et al (2009) New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 45:228–247CrossRefPubMed Eisenhauer EA, Therasse P, Bogaerts J et al (2009) New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 45:228–247CrossRefPubMed
19.
go back to reference Choi H, Charnsangavej C, Faria SC et al (2007) Correlation of computed tomography and positron emission tomography in patients with metastatic gastrointestinal stromal tumor treated at a single institution with imatinib mesylate: proposal of new computed tomography response criteria. J Clin Oncol 25:1753–1759CrossRefPubMed Choi H, Charnsangavej C, Faria SC et al (2007) Correlation of computed tomography and positron emission tomography in patients with metastatic gastrointestinal stromal tumor treated at a single institution with imatinib mesylate: proposal of new computed tomography response criteria. J Clin Oncol 25:1753–1759CrossRefPubMed
20.
go back to reference Schmidt N, Hess V, Zumbrunn T, Rothermundt C, Bongartz G, Potthast S (2013) Choi response criteria for prediction of survival in patients with metastatic renal cell carcinoma treated with anti-angiogenic therapies. Eur Radiol 23:632–639PubMed Schmidt N, Hess V, Zumbrunn T, Rothermundt C, Bongartz G, Potthast S (2013) Choi response criteria for prediction of survival in patients with metastatic renal cell carcinoma treated with anti-angiogenic therapies. Eur Radiol 23:632–639PubMed
21.
go back to reference Thiam R, Fournier LS, Trinquart L et al (2010) Optimizing the size variation threshold for the CT evaluation of response in metastatic renal cell carcinoma treated with sunitinib. Ann Oncol 21:936–941CrossRefPubMed Thiam R, Fournier LS, Trinquart L et al (2010) Optimizing the size variation threshold for the CT evaluation of response in metastatic renal cell carcinoma treated with sunitinib. Ann Oncol 21:936–941CrossRefPubMed
22.
go back to reference Terakawa T, Miyake H, Kusuda Y, Fujisawa M (2013) Expression level of vascular endothelial growth factor receptor-2 in radical nephrectomy specimens as a prognostic predictor in patients with metastatic renal cell carcinoma treated with sunitinib. Urol Oncol 31:493–498CrossRefPubMed Terakawa T, Miyake H, Kusuda Y, Fujisawa M (2013) Expression level of vascular endothelial growth factor receptor-2 in radical nephrectomy specimens as a prognostic predictor in patients with metastatic renal cell carcinoma treated with sunitinib. Urol Oncol 31:493–498CrossRefPubMed
23.
go back to reference Caldarella C, Muoio B, Isgrò MA, Porfiri E, Treglia G, Giovanella L (2014) The role of fluorine-18-fluorodeoxyglucose positron emission tomography in evaluating the response to tyrosine-kinase inhibitors in patients with metastatic primary renal cell carcinoma. Radiol Oncol 48:219–227CrossRefPubMedPubMedCentral Caldarella C, Muoio B, Isgrò MA, Porfiri E, Treglia G, Giovanella L (2014) The role of fluorine-18-fluorodeoxyglucose positron emission tomography in evaluating the response to tyrosine-kinase inhibitors in patients with metastatic primary renal cell carcinoma. Radiol Oncol 48:219–227CrossRefPubMedPubMedCentral
24.
go back to reference Farnebo J, Grybäck P, Harmenberg U et al (2014) Volumetric FDG-PET predicts overall and progression-free survival after 14 days of targeted therapy in metastatic renal cell carcinoma. BMC Cancer 14:408CrossRefPubMedPubMedCentral Farnebo J, Grybäck P, Harmenberg U et al (2014) Volumetric FDG-PET predicts overall and progression-free survival after 14 days of targeted therapy in metastatic renal cell carcinoma. BMC Cancer 14:408CrossRefPubMedPubMedCentral
Metadata
Title
Early Tumor Shrinkage Under Treatment with First-line Tyrosine Kinase Inhibitors as a Predictor of Overall Survival in Patients with Metastatic Renal Cell Carcinoma: a Retrospective Multi-Institutional Study in Japan
Authors
Hideaki Miyake
Akira Miyazaki
Satoshi Imai
Ken-ichi Harada
Masato Fujisawa
Publication date
01-04-2016
Publisher
Springer International Publishing
Published in
Targeted Oncology / Issue 2/2016
Print ISSN: 1776-2596
Electronic ISSN: 1776-260X
DOI
https://doi.org/10.1007/s11523-015-0385-6

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