Skip to main content
SpringerLink
Log in

Prognostic Significance of Early Tumor Shrinkage Under Second-Line Targeted Therapy for Metastatic Renal Cell Carcinoma: A Retrospective Multi-Institutional Study in Japan

  • Original Research Article
  • Published:
Molecular Diagnosis & Therapy Aims and scope Submit manuscript

Abstract

Background

The prognostic significance of early tumor shrinkage (ETS) under second-line targeted therapy for metastatic renal cell carcinoma (mRCC) has not been fully documented.

Aims

The objective of this study was to evaluate the impact of ETS induced by a second-line targeted agent on overall survival (OS) in mRCC patients.

Patients and Methods

This study retrospectively included 271 consecutive Japanese patients with mRCC who received second-line targeted therapy for at least 3 months. ETS was defined as the degree of tumor shrinkage at the first post-baseline radiological evaluation conducted 4–8 weeks after initiating second-line targeted therapy.

Results

Of the 271 patients, 26 had ETS from −100 to −50 %, 70 from −49 to −25 %, 84 from −24 to 0 %, and the remaining 91 failed to achieve a reduction in the tumor size. The median OS following the initiation of second-line targeted therapy stratified according to ETS was 45.8, 30.9, 22.1 and 14.2 months, respectively. Univariate analysis identified prior nephrectomy, the Memorial Sloan-Kettering Cancer Center (MSKCC) risk classification, C-reactive protein (CRP) level, number of metastatic organs, sarcomatoid feature, introduced second-line agent and ETS induced by a second-line agent as parameters significantly associated with OS, of which, only the MSKCC classification, CRP level and ETS appeared to have independent impacts on OS on multivariate analysis.

Conclusions

These findings suggest that ETS at the first post-baseline assessment under treatment with a second-line targeted agent could serve as a useful parameter with an independent impact on OS in mRCC patients receiving second-line targeted therapy.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Figlin R, Sternberg C, Wood CG. Novel agents and approaches for advanced renal cell carcinoma. J Urol. 2012;188:707–15.

    Article  CAS  PubMed  Google Scholar 

  2. Patard JJ, Pignot G, Escudier B, et al. ICUD-EAU International Consultation on Kidney Cancer 2010: treatment of metastatic disease. Eur Urol. 2011;60:684–90.

    Article  PubMed  Google Scholar 

  3. Calvo E, Ravaud A, Bellmunt J. What is the optimal therapy for patients with metastatic renal cell carcinoma who progress on an initial VEGFr-TKI? Cancer Treat Rev. 2013;39:366–74.

    Article  CAS  PubMed  Google Scholar 

  4. Oudard S, Elaidi RT. Sequential therapy with targeted agents in patients with advanced renal cell carcinoma: optimizing patient benefit. Cancer Treat Rev. 2012;38:981–7.

    Article  CAS  PubMed  Google Scholar 

  5. Rini BI, Escudier B, Tomczak P, et al. Comparative effectiveness of axitinib versus sorafenib in advanced renal cell carcinoma (AXIS): a randomised phase 3 trial. Lancet. 2011;378:1931–9.

    Article  CAS  PubMed  Google Scholar 

  6. Motzer RJ, Escudier B, Oudard S, et al. Efficacy of everolimus in advanced renal cell carcinoma: a double-blind, randomised, placebo-controlled phase III trial. Lancet. 2008;372:449–56.

    Article  CAS  PubMed  Google Scholar 

  7. Al-Marrawi MY, Rini BI, Harshman LC, et al. The association of clinical outcome to first-line VEGF-targeted therapy with clinical outcome to second-line VEGF-targeted therapy in metastatic renal cell carcinoma patients. Target Oncol. 2013;8:203–9.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Hutson TE, Escudier B, Esteban E, et al. Randomized phase III trial of temsirolimus versus sorafenib as second-line therapy after sunitinib in patients with metastatic renal cell carcinoma. J Clin Oncol. 2014;32:760–7.

    Article  CAS  PubMed  Google Scholar 

  9. Levy A, Menard J, Albiges L, et al. Second line treatment of metastatic renal cell carcinoma: the Institut Gustave Roussy experience with targeted therapies in 251 consecutive patients. Eur J Cancer. 2013;49:1898–904.

    Article  PubMed  Google Scholar 

  10. Motzer RJ, Bacik J, Murphy BA, et al. Interferon-alfa as a comparative treatment for clinical trials of new therapies against advanced renal cell carcinoma. J Clin Oncol. 2002;20:289–96.

    Article  CAS  PubMed  Google Scholar 

  11. Heng DY, Xie W, Regan MM, et al. 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. 2009;27:5794–9.

    Article  CAS  PubMed  Google Scholar 

  12. Seidel C, Busch J, Weikert S, et al. 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. 2012;48:1023–30.

    Article  CAS  PubMed  Google Scholar 

  13. Seidel C, Busch J, Weikert S, et al. Tumour shrinkage measured with first treatment evaluation under VEGF-targeted therapy as prognostic marker in metastatic renal cell carcinoma (mRCC). Br J Cancer. 2013;109:2998–3004.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Abel EJ, Culp SH, Tannir NM, et al. Early primary tumor size reduction is an independent predictor of improved overall survival in metastatic renal cell carcinoma patients treated with sunitinib. Eur Urol. 2011;60:1273–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Krajewski KM, Franchetti Y, Nishino M, et al. 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. 2014;19:507–14.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Halabi S, Rini B, Escudier B, Stadler WM, Small EJ. Progression-free survival as a surrogate endpoint of overall survival in patients with metastatic renal cell carcinoma. Cancer. 2014;120:52–60.

    Article  CAS  PubMed  Google Scholar 

  17. Grünwald V, McKay RR, Krajewski KM, et al. Depth of remission is a prognostic factor for survival in patients with metastatic renal cell carcinoma. Eur Urol. 2015;67:952–8.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Stein A, Bellmunt J, Escudier B, et al. Survival prediction in everolimus-treated patients with metastatic renal cell carcinoma incorporating tumor burden response in the RECORD-1 trial. Eur Urol. 2013;64:994–1002.

    Article  CAS  PubMed  Google Scholar 

  19. Claret L, Mercier F, Houk BE, et al. Modeling and simulations relating overall survival to tumor growth inhibition in renal cell carcinoma patients. Cancer Chemother Pharmacol. 2015;76:567–73.

    Article  CAS  PubMed  Google Scholar 

  20. Miyake H, Miyazaki A, Imai S, et al. 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. Target Oncol. 2016;11:175–82.

    Article  PubMed  Google Scholar 

  21. Eisenhauer EA, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009;45:228–47.

    Article  CAS  PubMed  Google Scholar 

  22. Petrelli F, Barni S. Surrogate end points and postprogression survival in renal cell carcinoma: an analysis of first-line trials with targeted therapies. Clin Genitourin Cancer. 2013;11:385–9.

    Article  PubMed  Google Scholar 

  23. Motzer RJ, Bukowski RM, Figlin RA, et al. Prognostic nomogram for sunitinib in patients with metastatic renal cell carcinoma. Cancer. 2008;113:1552–8.

    Article  CAS  PubMed  Google Scholar 

  24. Sacré A, Barthélémy P, Korenbaum C, et al. Prognostic factors in second-line targeted therapy for metastatic clear-cell renal cell carcinoma after progression on an anti-vascular endothelial growth factor receptor tyrosine kinase inhibitor. Acta Oncol. 2016;55:329–40.

    Article  PubMed  Google Scholar 

  25. Ko JJ, Xie W, Kroeger N, Lee JL, et al. The International Metastatic Renal Cell Carcinoma Database Consortium model as a prognostic tool in patients with metastatic renal cell carcinoma previously treated with first-line targeted therapy: a population-based study. Lancet Oncol. 2015;16:293–300.

    Article  PubMed  Google Scholar 

  26. Bruno R, Mercier F, Claret L. Evaluation of tumor size response metrics to predict survival in oncology clinical trials. Clin Pharmacol Ther. 2014;95:386–93.

    Article  CAS  PubMed  Google Scholar 

  27. Bender BC, Schindler E, Friberg LE. Population pharmacokinetic-pharmacodynamic modelling in oncology: a tool for predicting clinical response. Br J Clin Pharmacol. 2015;79:56–71.

    Article  CAS  PubMed  Google Scholar 

  28. van Houwelingen HC, Putter H. Dynamic predicting by landmarking as an alternative for multi-state modeling: an application to acute lymphoid leukemia data. Lifetime Data Anal. 2008;14:447–63.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Urology, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan

    Hideaki Miyake, Ken-ichi Harada & Masato Fujisawa

  2. Department of Urology, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu, 431-3192, Japan

    Hideaki Miyake & Seiichiro Ozono

Authors
  1. Hideaki Miyake
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ken-ichi Harada
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Seiichiro Ozono
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Masato Fujisawa
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Hideaki Miyake.

Ethics declarations

Conflict of interest

Hideaki Miyake, Ken-ichi Harada, Seiichiro Ozono, and Masato Fujisawa have nothing to disclose.

Funding

This study received no direct or indirect industry or pharmaceutical company support.

Ethical approval and informed consent

The design of this study was approved by the local Ethics Committee of Kobe University Graduate School of Medicine (approval no. 1082). All procedures performed in this study involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration. Informed consent was obtained from all individual participants included in the study.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Miyake, H., Harada, Ki., Ozono, S. et al. Prognostic Significance of Early Tumor Shrinkage Under Second-Line Targeted Therapy for Metastatic Renal Cell Carcinoma: A Retrospective Multi-Institutional Study in Japan. Mol Diagn Ther 20, 385–392 (2016). https://doi.org/10.1007/s40291-016-0206-3

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40291-016-0206-3

Keywords

Search

Navigation