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Comparison of the Impact of Immune-Related Adverse Events Due to Immune Checkpoint Inhibitor Dual Combination Therapy and Immune Checkpoint Inhibitor Plus Tyrosine Kinase Inhibitor Combination Therapy in Patients with Advanced Renal Cell Carcinoma

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Abstract

Background

The prognostic impact of immune-related adverse events during immune checkpoint inhibitor-based combination therapy for advanced renal cell carcinoma remains unclear, especially in terms of differences between regimens.

Objective

We aimed to clarify the prognostic impact of immune-related adverse events in patients with advanced renal cell carcinoma receiving immune checkpoint inhibitor dual combination therapy (IO-IO) or immune checkpoint inhibitor plus tyrosine kinase inhibitor combination therapy (IO-TKI).

Methods

We retrospectively evaluated the data of 148 patients who received immune checkpoint inhibitor-based combination therapy as first-line therapy. Patients were divided into two groups based on regimens, namely IO-IO and IO-TKI. The associations between immune-related adverse event development and outcomes, such as progression-free survival, overall survival, and objective response rate, were compared between the two groups.

Results

In the IO-IO and IO-TKI groups, 67 of 91 (74%) and 31 of 57 (54%) patients, respectively, experienced at least one immune-related adverse event and the rate was significantly higher in the IO-IO group (p = 0.0204), where immune-related adverse events development was significantly associated with longer progression-free survival (p < 0.0001) and overall survival (p = 0.0102), and a higher objective response rate (p = 0.0028). A multivariate analysis revealed immune-related adverse event development as an independent factor for longer progression-free survival (hazard ratio, 0.25; p < 0.0001) and overall survival (hazard ratio, 0.42; p = 0.0287). There were no significant associations between immune-related adverse events and progression-free survival, overall survival, or objective response rate in the IO-TKI group.

Conclusions

The development of immune-related adverse events was positively associated with the outcome of patients with advanced renal cell carcinoma treated with IO-IO combination therapy; no such correlation was observed for IO-TKI combination therapy.

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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

    Hiroki Ishihara, Yuki Nemoto, Kazutaka Nakamura, 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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Correspondence to Hiroki Ishihara.

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Funding

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

Conflicts of interest

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, 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 the 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 the Impact of Immune-Related Adverse Events Due to Immune Checkpoint Inhibitor Dual Combination Therapy and Immune Checkpoint Inhibitor Plus Tyrosine Kinase Inhibitor Combination Therapy in Patients with Advanced Renal Cell Carcinoma. Targ Oncol 18, 159–168 (2023). https://doi.org/10.1007/s11523-022-00940-8

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