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Efficacy of fourth-line targeted therapy in patients with metastatic renal cell carcinoma: a retrospective analysis

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Abstract

Introduction

Evidence for sequencing targeted therapy (TT) in patients with metastatic renal cell carcinoma (mRCC) beyond third line is limited. Treatment decisions for these sequence options are largely based on individual preferences and experience. The aim of this study was to describe the efficacy and toxicity of fourth-line TT.

Materials and methods

We retrospectively reviewed patients treated with fourth-line TT for mRCC after failure of previous treatment lines at a German academic high-volume center. Out of 406 patients treated in first line, 56 patients (14.8 %) were identified with more than three lines of TT. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan–Meier method. Cox proportional hazards models were applied to explore predictors of PFS and OS in uni- and multivariable analysis.

Results

For the fourth-line treatment, disease control rate was 35.7 %. Median OS from beginning of first-line therapy was 47.4 months (IQR 31.0–76.5). Primary resistance at first-line TT, metastatic disease at initial diagnosis and an intermediate MSKCC score were independent predictors of shorter OS from start of first-line TT. Median OS from the time of initiation of fourth-line therapy was 10.5 months (IQR 5.6–22.6). The corresponding median PFS for fourth-line TT was 3.2 months (IQR 1.6–8.0) and was not correlated with treatment response in first-line TT. The rate of toxicity-induced treatment termination was 16.1 %. Limitations are the retrospective and unicentric design with a limited number of patients.

Conclusions

Patients might benefit from subsequent treatment lines independently from treatment response in first line.

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Acknowledgments

B Ralla is a participant in the Charité—Junior Clinical Scientist Program funded by the Charité—Universitaetsmedizin Berlin and the Berlin Institute of Health. J Busch is a participant in the Charité—Twinning Grant Program funded by the Charité—Universitaetsmedizin Berlin and the Berlin Institute of Health.

Author contributions

B Ralla contributed to data collection, data analysis and manuscript writing; J Busch and C Kempkensteffen analyzed the data and edited the manuscript; K Miller, A Magheli and S Hinz edited the manuscript; B Erber collected the data; A Flörcken collected the data and edited the manuscript.

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Authors and Affiliations

  1. Department of Urology, Charité Universitaetsmedizin Berlin, Charité Platz 1, 10117, Berlin, Germany

    Bernhard Ralla, Barbara Erber, Irena Goranova, Luise von der Aue, Stefan Hinz, Carsten Kempkensteffen, Ahmed Magheli, Kurt Miller & Jonas Busch

  2. Department of Hematology, Oncology and Tumor Immunology, Charité Universitaetsmedizin Berlin, Berlin, Germany

    Anne Floercken

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  1. Bernhard Ralla
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  2. Barbara Erber
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  3. Irena Goranova
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  4. Luise von der Aue
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  5. Anne Floercken
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  6. Stefan Hinz
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  7. Carsten Kempkensteffen
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  8. Ahmed Magheli
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  9. Kurt Miller
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  10. Jonas Busch
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Corresponding author

Correspondence to Bernhard Ralla.

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Conflicts of interest

B Ralla and L von der Aue: none; J Busch: advisor to Pfizer, Novartis, GSK, Roche, Mologen; K Miller: advisor to Pfizer, Novartis, Roche, BMS, MSD; A Magheli advisor to Pfizer; B Erber: advisor to Pfizer, Novartis, GSK, Roche; C Kempkensteffen advisor to Astellas, Jansen-Cilag, Bayer, Pfizer; S Hinz: advisor to Pfizer and Novartis; A Flörcken: advisor to Bayer, Pfizer; I Goranova: advisor to Novartis.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

Informed consent

The study was approved by the Charité – University Hospital Ethics Committee. Informed consent was obtained from the participants.

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Ralla, B., Erber, B., Goranova, I. et al. Efficacy of fourth-line targeted therapy in patients with metastatic renal cell carcinoma: a retrospective analysis. World J Urol 34, 1147–1154 (2016). https://doi.org/10.1007/s00345-015-1740-z

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  • DOI: https://doi.org/10.1007/s00345-015-1740-z

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