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Changes in Real-World Outcomes in Patients with Metastatic Renal Cell Carcinoma from the Molecular-Targeted Therapy Era to the Immune Checkpoint Inhibitor Era

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Abstract

Background

Knowledge of changes in the outcome in patients with metastatic renal cell carcinoma from the molecular-targeted therapy era to the immune checkpoint inhibitor (ICI) era remains limited in the real-world setting.

Objectives

We aimed to clarify outcome changes from the previous molecular-targeted therapy era to the current ICI era in patients with metastatic renal cell carcinoma using multi-institution real-world data.

Methods

We retrospectively evaluated 415 patients with metastatic renal cell carcinoma who received first-line systemic therapy at five Japanese institutions between January 2008 and August 2021. We divided the patients into two groups based on the treatment era: molecular-targeted therapy era (January 2008–August 2018) and ICI era (September 2018–August 2021). According to the era, progression-free survival, overall survival, and objective response rate from first-line systemic therapy were compared.

Results

Overall, 304 (73.3%) and 111 (26.7%) patients were categorized into the molecular-targeted therapy and ICI eras, respectively. The proportion of patients without prior nephrectomy (p = 0.0030) or those with low Karnofsky Performance Status scores [≤ 70] (p = 0.0258) were significantly higher in the ICI era group. The patients in the ICI era group had significantly longer overall survival (median: not reached vs 23.2 months, p = 0.0001) and a higher objective response rate (47.8% vs 24.7%, p < 0.0001) than those in the molecular-targeted therapy era group, and progression-free survival tended to be longer in the ICI era group (median: 13.3 vs 8.75 months, p = 0.0579). Multivariate analysis further showed that the treatment era (ICI vs molecular-targeted therapy) was an independent factor for overall survival and objective response (both, p < 0.0001).

Conclusions

The present multi-institution real-world data showed the improved outcome of previously untreated patients with metastatic renal cell carcinoma in the ICI era group compared with that in the molecular-targeted therapy era group. These findings strongly encourage the use of ICI-based treatment for patients with metastatic renal cell carcinoma in the real-world setting. Further studies with extended follow-up periods are needed to confirm our findings.

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Acknowledgments

The authors are grateful to Ms. Nobuko Hata, from the Department of Urology, Tokyo Women’s Medical University, for secretarial assistance and to the patients from the participating institutions.

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Authors and Affiliations

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

    Hiroki Ishihara, Hirohito Kobayashi & Tsunenori Kondo

  2. Department of Urology, Saiseikai Kawaguchi General Hospital, Kawaguchi, Saitama, Japan

    Yuki Nemoto & Yasunobu Hashimoto

  3. Department of Urology, Jyoban Hospital, Iwaki, Fukushima, Japan

    Kazutaka Nakamura & Hiroaki Shimmura

  4. Department of Urology, Saiseikai Kurihashi Hospital, Kuki, Saitama, Japan

    Hidekazu Tachibana

  5. Department of Urology, Tokyo Women’s Medical University, Tokyo, Japan

    Hironori Fukuda, Kazuhiko Yoshida, Junpei Iizuka, Kazunari Tanabe & Toshio Takagi

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  1. Hiroki Ishihara
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  2. Yuki Nemoto
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  3. Kazutaka Nakamura
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Corresponding author

Correspondence to Hiroki Ishihara.

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Funding

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

Conflict of interest

Toshio Takagi received a speaker honorarium from Bristol-Myers Squibb and Ono Pharmaceutical. Tsunenori Kondo received a speaker honorarium from Pfizer, Novartis, Bristol-Myers Squibb, and Ono Pharmaceutical. Hiroki Ishihara, Yuki Nemoto, Kazutaka Nakamura, Hidekazu Tachibana, Hironori Fukuda, Kazuhiko Yoshida, Hirohito Kobayashi, Junpei Iizuka, Hiroaki Shimmura, Yasunobu Hashimoto, and Kazunari Tanabe declare that they have no conflict of interest.

Ethics approval

The study protocol was approved by the Institutional Review Boards of Tokyo Women’s Medical University, Tokyo Women’s Medical University Medical Center East, Saiseikai Kawaguchi General Hospital, Saiseikai Kurihashi Hospital, and Jyoban Hospital (ID: 2020-0009). This study conforms to the ethical guidelines of the 1964 Declaration of Helsinki. The requirement for written informed consent was waived because of the retrospective observational nature of the study.

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All authors contributed to the study conception and design, data collection, and data analysis. HI wrote the first draft of the manuscript, and all authors critically revised the manuscript for important intellectual content and approved the version to be published.

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Ishihara, H., Nemoto, Y., Nakamura, K. et al. Changes in Real-World Outcomes in Patients with Metastatic Renal Cell Carcinoma from the Molecular-Targeted Therapy Era to the Immune Checkpoint Inhibitor Era. Targ Oncol 17, 307–319 (2022). https://doi.org/10.1007/s11523-022-00879-w

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