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International Journal of Clinical Oncology

, Volume 23, Issue 3, pp 559–567 | Cite as

Efficacy and safety of third-line molecular-targeted therapy in metastatic renal cell carcinoma resistant to first-line vascular endothelial growth factor receptor tyrosine kinase inhibitor and second-line therapy

  • Hiroki Ishihara
  • Toshio Takagi
  • Tsunenori Kondo
  • Hidekazu Tachibana
  • Kazuhiko Yoshida
  • Kenji Omae
  • Junpei Iizuka
  • Hirohito Kobayashi
  • Kazunari Tanabe
Original Article
  • 194 Downloads

Abstract

Background

The number of studies evaluating the efficacy and safety of third-line molecular-targeted therapy for metastatic renal cell carcinoma (mRCC) is limited.

Methods

The data for 48 patients with disease progression after first-line vascular endothelial growth factor receptor tyrosine kinase inhibitor (TKI) and second-line targeted therapy were evaluated. Patients with prior cytokine therapy were excluded. Overall survival (OS) after first- and second-line therapy initiation was compared between patients with and without third-line therapy. In addition, dose-limiting toxicities (DLTs) were evaluated.

Results

Twenty-two of 48 patients (45.8%) received third-line therapy, and TKI and mammalian target of rapamycin inhibitor were each administered in 11 patients (50%). Patients with third-line therapy had significantly longer median OS after first-line therapy (26.6 vs. 14.6 months, p = 0.0010) and second-line therapy (18.2 vs. 7.4 months, p < 0.0001) compared to those without third-line therapy. Multivariate analysis showed that the use of third-line therapy following second-line therapy was an independent prognosticator for longer OS (hazard ratio 0.29, 95% confidence interval 0.14–0.58, p = 0.0005). The median progression-free survival and OS after third-line therapy was 2.76 and 8.71 months, respectively. Although a high frequency of DLTs was observed (n = 10, 45.5%), the frequencies were similar among the sequential therapies.

Conclusions

Third-line therapy has a beneficial therapeutic effect in patients with mRCC that is resistant to previous therapies. However, there is a need to evaluate in detail the high frequency of adverse events, including DLTs.

Keywords

Renal cell carcinoma Targeted therapy Third-line therapy Tyrosine kinase inhibitor mTORi Metastasis 

Notes

Acknowledgements

The authors thank Editage for English language editing and Nobuko Hata for secretarial support.

Compliance with ethical standards

Conflict of interest

Tsunenori Kondo received honoraria from Pfizer, Bayer, and Novartis. None of the other authors have any conflicts of interest to declare.

Supplementary material

10147_2018_1241_MOESM1_ESM.tif (139 kb)
Fig. S1a–b. Overall survival after first- and second-line therapy according to the use of third-line therapy in 34 patients with a diagnosis of clear-cell carcinoma. Patients with third-line therapy (n = 16) had a significantly longer overall survival after first- and second-line therapy than those without third-line therapy. a Median overall survival after first-line therapy: 30.6 vs. 18.5 months, p = 0.0110. b Median overall survival after second-line therapy: 21.8 vs. 8.34 months, p = 0.0013. (TIFF 138 kb)
10147_2018_1241_MOESM2_ESM.tif (74 kb)
Fig. S2. Waterfall plot analysis. The waterfall plot analysis shows the objective response rate according to the third-line agents used in each patient. mTORi mammalian target of rapamycin inhibitor (TIFF 69 kb)

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Copyright information

© Japan Society of Clinical Oncology 2018

Authors and Affiliations

  1. 1.Department of Urology, Kidney CenterTokyo Women’s Medical UniversityTokyoJapan
  2. 2.Department of UrologyTokyo Women’s Medical University Medical Center EastTokyoJapan
  3. 3.Department of Healthcare EpidemiologyKyoto University Graduate School of Medicine/School of Public HealthKyotoJapan
  4. 4.Center for Innovative Research for Communities and Clinical ExcellenceFukushima Medical UniversityFukushima CityJapan

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