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Comparison of Outcomes Between Therapeutic Combinations Based on Immune Checkpoint Inhibitors or Tyrosine Kinase Inhibitor Monotherapy for First-Line Therapy of Patients with Advanced Renal Cell Carcinoma Outside of Clinical Trials: A Real-World Retrospective Multi-Institutional Study

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Abstract

Background

Clinical trials have demonstrated the superior efficacy of immune checkpoint inhibitor (ICI)-based combination therapy over sunitinib, a multi-target tyrosine kinase inhibitor (TKI), in patients with advanced renal cell carcinoma. However, such benefits have not been elucidated in populations outside of clinical trials.

Methods

We retrospectively evaluated data from 467 patients with advanced renal cell carcinoma who received ICI-based combination therapy or TKIs, as first-line therapy. Clinical outcome was compared between ICI-based combination therapy and TKIs in each population divided according to trial eligibility.

Results

Among 152 patients treated with ICI-based combination therapy and 315 patients treated with TKIs, 76 (50.0%) and 156 (49.5%) were trial ineligible, respectively. Overall survival (p = 0.0072) and objective response rate (p < 0.0001) were significantly higher in ICI-based combination therapy than in TKIs, but progression-free survival was comparable (p = 0.681). In the trial-eligible population, overall survival was longer (p = 0.0906) and the objective response rate was significantly higher (p = 0.0124) in ICI-based combination therapy than in TKIs. In the trial-ineligible population, overall survival (p = 0.0208) and objective response rate (p = 0.0006) were significantly higher with ICI-based combination therapy than with TKIs. A multivariate analysis also showed that ICI-based combination therapy was independently associated with prolonged overall survival (hazard ratio, 0.47; p = 0.0016). Regardless of trial eligibility, progression-free survival did not differ between ICI-based combination therapy and TKIs (trial eligible: p = 0.287; trial ineligible: p = 0.0708).

Conclusions

The present study, using real-world data, provides evidence indicating the therapeutic benefit of ICI-based combination therapy over TKIs for advanced renal cell carcinoma was more statistically significant in the trial-ineligible population than in the trial-eligible population.

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Acknowledgements

The authors thank Ms. Nobuko Hata (Department of Urology, Tokyo Women’s Medical University) for her secretarial efforts.

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Authors and Affiliations

  1. Department of Urology, Tokyo Women’s Medical University Adachi Medical Center, 4-33-1 Kouhoku, Adachi-ku, Tokyo, Japan

    Hiroki Ishihara, Yuki Nemoto, Hirohito Kobayashi & Tsunenori Kondo

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

    Yuki Nemoto, Kazutaka Nakamura, Takashi Ikeda, Hironori Fukuda, Kazuhiko Yoshida, Junpei Iizuka & Toshio Takagi

  3. Department of Urology, Jyoban Hospital, Uenodai 57, Joban Kamiyunagayamachi, Iwaki, Fukushima, Japan

    Kazutaka Nakamura & Hiroaki Shimmura

  4. Department of Urology, Saiseikai Kazo Hospital, 1680 Kamitakayanagi, Kazo, Saitama, Japan

    Hidekazu Tachibana

  5. Department of Urology, Saiseikai Kawaguchi General Hospital, 5-11-5 Nishikawaguchi, Kawaguchi, Saitama, Japan

    Yasunobu Hashimoto

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  1. Hiroki Ishihara
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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.

Conflicts of interest/competing interests

Toshio Takagi received honoraria from BristolMyers Squibb and Ono Pharmaceutical. Tsunenori Kondo received honoraria from Pfizer, Novartis, Bristol-Myers Squibb, and Ono Pharmaceutical. Hiroki Ishihara, Yuki Nemoto, Kazutaka Nakamura, Hidekazu Tachibana, Takashi Ikeda, Hironori Fukuda, Kazuhiko Yoshida, Hirohito Kobayashi, Junpei Iizuka, Hiroaki Shimmura, and Yasunobu Hashimoto have no conflicts of interest that are directly relevant to the content of this article.

Ethics approval

The study protocol was approved by the Institutional Ethics Review Board of each institution (Tokyo Women’s Medical University, Tokyo Women’s Medical University Adachi Medical Center, Saiseikai Kawaguchi General Hospital, Saiseikai Kazo Hospital, and Jyoban Hospital; ID: 2020-0009). The present study was performed according to the guidelines of the 1964 Declaration of Helsinki and its later amendments. Owing to the retrospective observational nature of this study, the need for informed consent was waived.

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All authors contributed to this study’s conception and design, data collection, and analysis. The first draft of the manuscript was written by HI and all authors commented on the previous drafts of the manuscript. All authors read and approved the final version of the manuscript.

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Ishihara, H., Nemoto, Y., Nakamura, K. et al. Comparison of Outcomes Between Therapeutic Combinations Based on Immune Checkpoint Inhibitors or Tyrosine Kinase Inhibitor Monotherapy for First-Line Therapy of Patients with Advanced Renal Cell Carcinoma Outside of Clinical Trials: A Real-World Retrospective Multi-Institutional Study. Targ Oncol 18, 209–220 (2023). https://doi.org/10.1007/s11523-023-00956-8

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