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Immediate Progressive Disease in Patients with Metastatic Renal Cell Carcinoma Treated with Nivolumab: a Multi-Institution Retrospective Study

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Abstract

Background

Investigations on rapid disease progression in patients with urologic malignancies treated with immune checkpoint inhibitors are currently lacking.

Objective

The objective of this study was to assess cases of rapid disease progression/immediate development of progressive disease (immediate PD) in patients with pretreated metastatic renal cell carcinoma (mRCC) treated with nivolumab.

Patients and Methods

Forty patients were retrospectively evaluated. Immediate PD within the initial two cycles of nivolumab therapy was clinically or objectively diagnosed. Clinical diagnosis was defined as an acceleration of symptoms directly caused by tumor growth or systematic worsening of the general condition, such as cachexia. Objective diagnosis was based on imaging evaluation using the Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1).

Results

Seven patients (17.5%) developed immediate PD. For these patients, the median time from the initiation of nivolumab treatment to PD was 14 days; all seven patients subsequently died from the cancer. Progression-free survival (0.66 vs. 10.5 months; p < 0.0001) and overall survival (1.41 months vs. not reached; p < 0.0001) were significantly shorter in patients with immediate PD than in those without immediate PD. Further, female sex (p = 0.0434), poor Memorial Sloan Kettering Cancer Center (MSKCC) prognostic score (p = 0.0263), and shorter prior-line time to progression (p = 0.0218) were associated with immediate PD.

Conclusions

The development of immediate PD in mRCC patients treated with nivolumab can severely worsen patient prognosis. Sex, MSKCC score, and prior-line time to progression may be involved in the development of immediate PD. Prospective studies are needed to further assess these findings.

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Acknowledgements

The authors thank Dr. Kana Iwamoto (Department of Urology, Tokyo Women’s Medical University Medical Center East) for assisting with the data collection and Nobuko Hata (Department of Urology, Tokyo Women’s Medical University) for secretarial work.

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Authors and Affiliations

  1. Department of Urology, Tokyo Women’s Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, 162-8666, Japan

    Hiroki Ishihara, Toshio Takagi, Hironori Fukuda, Kazuhiko Yoshida, Junpei Iizuka, Hirohito Kobayashi & Kazunari Tanabe

  2. Department of Urology, Tokyo Women’s Medical University Medical Center East, 2-1-10 Nishiogu, Arakawa-ku, Tokyo, 116-8567, Japan

    Tsunenori Kondo & Hidekazu Tachibana

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  1. Hiroki Ishihara
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  2. Tsunenori Kondo
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Correspondence to Tsunenori Kondo.

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Funding

No external funding was used in the preparation of this manuscript.

Disclosure of Conflict of Interest

Tsunenori Kondo received honoraria from Pfizer, Bayer, and Novartis. Hiroki Ishihara, Toshio Takagi, Hidekazu Tachibana, Hironori Fukuda, Kazuhiko Yoshida, Junpei Iizuka, Hirohito Kobayashi, and Kazunari Tanabe declare that they have no conflicts of interest that might be relevant to the contents of this manuscript.

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Ishihara, H., Kondo, T., Takagi, T. et al. Immediate Progressive Disease in Patients with Metastatic Renal Cell Carcinoma Treated with Nivolumab: a Multi-Institution Retrospective Study. Targ Oncol 13, 611–619 (2018). https://doi.org/10.1007/s11523-018-0591-0

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  • DOI: https://doi.org/10.1007/s11523-018-0591-0

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