Advertisement

External validation of nomograms for prediction of progression-free survival and liver toxicity in patients with advanced renal cell carcinoma treated with pazopanib

  • Yasuyoshi Okamura
  • Nobuyuki HinataEmail author
  • Tomoaki Terakawa
  • Junya Furukawa
  • Kenichi Harada
  • Yuzo Nakano
  • Ichiro Nakamura
  • Takaaki Inoue
  • Takayoshi Ogawa
  • Masato Fujisawa
Original Article
  • 94 Downloads

Abstract

Background

Nomograms have been developed for the prediction of progression-free survival (PFS) and liver toxicity in patients with advanced renal cell carcinoma (RCC) who are treated with pazopanib. The objectives of this study were to review clinical outcomes, to perform an external validation of these nomograms and to develop a new nomogram in Japanese patients.

Methods

A retrospective chart review of 150 Japanese patients with advanced RCC who received pazopanib at Kobe University Hospital and affiliated hospitals from March 2014 to June 2017 was performed. We evaluated the clinical efficacy and safety of pazopanib using logistic regression analysis to analyze the prognostic factors for overall survival (OS) and PFS. For nomogram validation, concordance index (C-index) and calibration were used.

Results

The median PFS and OS in this study was 13.1 and 37.4 months, respectively. Multivariate analyses identified prognostic factors for OS (number of metastasis, white blood cell (WBC) count and lactate dehydrogenase) and PFS (number of metastasis, WBC count). The C-index of nomograms for 12-month PFS was 0.598. The C-index of nomograms for liver toxicity was 0.558. A new Nomogram for predicting 12-month PFS for patients who received pazopanib was developed and performed internal validation. The C-index of the nomogram was 0.768.

Conclusion

The clinical effect and safety of pazopanib reported in this study was similar to previous studies. This study suggests careful application of nomograms to Japanese patients treated with pazopanib. We have developed a new nomogram for predicting 12-month PFS with pazopanib therapy from Japanese patients.

Keywords

Renal cell carcinoma Pazopanib Nomogram Validation Japanese 

Notes

Acknowledgements

We thank all the patients, their families and investigators who participated in this study. We thank Michael W. Kattan for provision of the logistic regression model for the liver toxicity nomogram. We thank Sarah Bubeck, Ph.D., from Edanz Group (http://www.edanzediting.com/ac), for editing a draft of this manuscript.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

References

  1. 1.
    Kane CJ, Mallin K, Ritchey J et al (2008) Renal cell cancer stage migration: analysis of the National Cancer Data Base. Cancer 113:78–83CrossRefPubMedGoogle Scholar
  2. 2.
    Kjaer M, Iversen P, Hvidt V et al (1987) A randomized trial of postoperative radiotherapy versus observation in stage II and III renal adenocarcinoma. A study by the Copenhagen Renal Cancer Study Group. Scand J Urol Nephrol 21(4):285–289CrossRefPubMedGoogle Scholar
  3. 3.
    Motzer RJ, Russo P (2000) Systemic therapy for renal cell carcinoma. J Urol 163(2):408–417CrossRefPubMedGoogle Scholar
  4. 4.
    Frampton JE (2017) Pazopanib: a review in advanced renal cell carcinoma. Target Oncol 12:543–554CrossRefPubMedGoogle Scholar
  5. 5.
    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(1):289–296CrossRefPubMedGoogle Scholar
  6. 6.
    Ljungberg B, Bensalah K, Bex A et al (2018) EAU guidelines on renal cell carcinoma 2018. http://uroweb.org/guideline/renal-cellcarcinoma/. Accessed 15 Jun 2018
  7. 7.
    National Comprehensive Cancer Network (2018) NCCN clinical practice guidelines in oncology: kidney cancer. https://www.nccn.org/professionals/physician_gls/pdf/kidney.pdf. Accessed 15 Jun 2018
  8. 8.
    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 27:5794–5799CrossRefPubMedGoogle Scholar
  9. 9.
    Motzer RJ, Bukowski RM, Figlin RA et al (2008) Prognostic nomogram for sunitinib in patients with metastatic renal cell carcinoma. Cancer 113:1552–1558CrossRefPubMedGoogle Scholar
  10. 10.
    Kattan MW, Sternberg CN, Mehmud F et al (2015) Development and validation of a prognostic nomogram for progression-free survival in patients with advanced renal cell carcinoma treated with pazopanib. Oncology 89:235–241CrossRefPubMedGoogle Scholar
  11. 11.
    Kattan MW, Winette TA, Powles T et al (2017) Development of a prognostic nomogram for liver toxicity in patients treated with pazopanib. J Clin Oncol 35:6_suppl 455–455CrossRefGoogle Scholar
  12. 12.
    Sternberg CN, Davis ID, Mardiak J et al (2010) Pazopanib in locally advanced or metastatic renal cell carcinoma: results of a randomized phase III trial. J Clin Oncol 28(6):1061–1068CrossRefPubMedGoogle Scholar
  13. 13.
    Motzer RJ, Hutson TE, McCann L et al (2014) Overall survival in renal cell carcinoma with pazopanib versus sunitinib. N Engl J Med 370(18):1769–1770CrossRefPubMedGoogle Scholar
  14. 14.
    Tomita Y, Shinohara N, Yuasa T et al (2010) Overall survival and updated results from a phase II study of sunitinib in Japanese patients with metastatic renal cell carcinoma. Jpn J Clin Oncol 40:1166–1172CrossRefPubMedGoogle Scholar
  15. 15.
    Lee S, Bang Y, Mainwaring P et al (2014) Sunitinib in metastatic renal cell carcinoma: an ethnic Asian subpopulation analysis for safety and efficacy. Asia Pac J Clin Oncol 10(3):237–245CrossRefPubMedGoogle Scholar
  16. 16.
    Choueiri TK, Garcia JA, Elson P et al (2007) Clinical factors associated with outcome in patients with metastatic clear-cell renal cell carcinoma treated with vascular endothelial growth factor-targeted therapy. Cancer 110:543–550CrossRefPubMedGoogle Scholar
  17. 17.
    Negrier S, Escudier B, Gomez F et al (2002) Prognostic factors of survival and rapid progression in 782 patients with metastatic renal carcinomas treated by cytokines: a report from the Groupe Francais d’Immunotherapie. Ann Oncol 13:1460–1468CrossRefPubMedGoogle Scholar
  18. 18.
    Manola J, Royston P, Elson P et al (2011) Prognostic model for survival in patients with metastatic renal cell carcinoma: results from the international kidney cancer working group. Clin Cancer Res 17:5443–5450CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Climent MA, Muñoz-Langa J, Basterretxea-Badiola L et al (2018) Systematic review and survival meta-analysis of real world evidence on first-line pazopanib for metastatic renal cell carcinoma. Crit Rev Oncol Hematol 121:45–50CrossRefPubMedGoogle Scholar
  20. 20.
    Powles T, Bracarda S, Chen M et al (2015) Characterisation of liver chemistry abnormalities associated with pazopanib monotherapy: a systematic review and meta-analysis of clinical trials in advanced cancer patients. Eur J Cancer 51(10):1293–1302CrossRefPubMedGoogle Scholar
  21. 21.
    Yoo C, Kim JE, Lee JL et al (2010) The efficacy and safety of sunitinib in Korean patients with advanced renal cell carcinoma: high incidence of toxicity leads to frequent dose reduction. Jpn J Clin Oncol 40:980–985CrossRefPubMedGoogle Scholar
  22. 22.
    Guo J, Jin J, Huang Y et al (2013) Comparison of PFS and safety for Asian compared to North American and European populations in the phase III trial of pazopanib versus sunitinib in patients with treatment-naive RCC (COMPARZ). J Clin Oncol 31(Suppl 6):Abstr 366CrossRefGoogle Scholar

Copyright information

© Japan Society of Clinical Oncology 2019

Authors and Affiliations

  • Yasuyoshi Okamura
    • 1
  • Nobuyuki Hinata
    • 1
    Email author
  • Tomoaki Terakawa
    • 1
  • Junya Furukawa
    • 1
  • Kenichi Harada
    • 1
  • Yuzo Nakano
    • 1
  • Ichiro Nakamura
    • 2
  • Takaaki Inoue
    • 3
  • Takayoshi Ogawa
    • 4
  • Masato Fujisawa
    • 1
  1. 1.Department of UrologyKobe University Graduate School of MedicineKobeJapan
  2. 2.Department of Urology, Kobe City Hospital OrganizationKobe City Medical Center West HospitalKobeJapan
  3. 3.Department of UrologyHyogo Cancer CenterAkashiJapan
  4. 4.Department of UrologyHimeji Red Cross HospitalHimejiJapan

Personalised recommendations