Research Article

Validation of a drug-based score in advanced urothelial carcinoma treated with pembrolizumab

Department of Urology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan

Department of Urology, Kyorin University School of Medicine, 6-20-2 Shinkawa, Mitaka-shi, Tokyo, 181-8611, Japan

‡Contributed equally

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Taketo Kawai

*Author for correspondence: Tel.: +81 3 3964 1211;

E-mail Address: taketokawai@yahoo.co.jp

https://orcid.org/0000-0002-7279-2874

Department of Urology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan

Department of Urology, Teikyo University School of Medicine, 2-11-1 Kaga, Itabashi-ku, Tokyo, 173-8605, Japan

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Sebastiano Buti‡

https://orcid.org/0000-0003-0876-0226

Medicine & Surgery Department, University of Parma, Via Gramsci 14, Parma, 43126, Italy

‡Contributed equally

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Melissa Bersanelli

**Author for correspondence: Tel.: +39 0521 702316;

E-mail Address: bersamel@libero.it

https://orcid.org/0000-0002-6527-6281

Medical Oncology Unit, University Hospital of Parma, Via Gramsci 14, Parma, 43126, Italy

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Yukari Uemura

https://orcid.org/0000-0002-3013-7775

Biostatistics Section, Department of Data Science, Center of Clinical Sciences, National Center for Global Health & Medicine, 1-21-1 Toyama, Shinjuku-ku, Tokyo, 162-8655, Japan

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Kenjiro Kishitani

Department of Urology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan

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Jimpei Miyakawa

Department of Urology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan

Department of Urology, Kyorin University School of Medicine, 6-20-2 Shinkawa, Mitaka-shi, Tokyo, 181-8611, Japan

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Kazuma Sugimoto

Department of Urology, Kyorin University School of Medicine, 6-20-2 Shinkawa, Mitaka-shi, Tokyo, 181-8611, Japan

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Yu Nakamura

Department of Urology, Kyorin University School of Medicine, 6-20-2 Shinkawa, Mitaka-shi, Tokyo, 181-8611, Japan

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Fusako Niimi

Department of Urology, Teikyo University School of Medicine, 2-11-1 Kaga, Itabashi-ku, Tokyo, 173-8605, Japan

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Tomoyuki Kaneko

https://orcid.org/0000-0002-5762-7563

Department of Urology, Teikyo University School of Medicine, 2-11-1 Kaga, Itabashi-ku, Tokyo, 173-8605, Japan

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Jun Kamei

https://orcid.org/0000-0002-0069-7392

Department of Urology, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke-shi, Tochigi, 329-0498, Japan

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Daisuke Obinata

Department of Urology, Nihon University School of Medicine, 30-1 Oyaguchi Kami-cho, Itabashi-ku, Tokyo, 173-8610, Japan

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Kenya Yamaguchi

Department of Urology, Nihon University School of Medicine, 30-1 Oyaguchi Kami-cho, Itabashi-ku, Tokyo, 173-8610, Japan

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Shigenori Kakutani

Division of Urology, Mitsui Memorial Hospital, 1 Kanda-izumi-cho, Chiyoda-ku, Tokyo, 101-8643, Japan

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Koichiro Kanazawa

Department of Urology, The Fraternity Memorial Hospital, 2-1-11 Yokozuna, Sumida-ku, Tokyo, 130-8587, Japan

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Yuriko Sugihara

Department of Urology, The Fraternity Memorial Hospital, 2-1-11 Yokozuna, Sumida-ku, Tokyo, 130-8587, Japan

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Mayuko Tokunaga

Department of Urology, The Fraternity Memorial Hospital, 2-1-11 Yokozuna, Sumida-ku, Tokyo, 130-8587, Japan

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Yoshiyuki Akiyama

https://orcid.org/0000-0003-1439-5640

Department of Urology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan

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Yuta Yamada

https://orcid.org/0000-0002-9698-4301

Department of Urology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan

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Yusuke Sato

Department of Urology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan

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Daisuke Yamada

https://orcid.org/0000-0002-2296-6653

Department of Urology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan

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Yutaka Enomoto

Division of Urology, Mitsui Memorial Hospital, 1 Kanda-izumi-cho, Chiyoda-ku, Tokyo, 101-8643, Japan

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Hiroaki Nishimatsu

Department of Urology, The Fraternity Memorial Hospital, 2-1-11 Yokozuna, Sumida-ku, Tokyo, 130-8587, Japan

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Tetsuya Fujimura

Department of Urology, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke-shi, Tochigi, 329-0498, Japan

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Hiroshi Fukuhara

https://orcid.org/0000-0002-5404-600X

Department of Urology, Kyorin University School of Medicine, 6-20-2 Shinkawa, Mitaka-shi, Tokyo, 181-8611, Japan

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Tohru Nakagawa

https://orcid.org/0000-0003-4041-7241

Department of Urology, Teikyo University School of Medicine, 2-11-1 Kaga, Itabashi-ku, Tokyo, 173-8605, Japan

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Satoru Takahashi

Department of Urology, Nihon University School of Medicine, 30-1 Oyaguchi Kami-cho, Itabashi-ku, Tokyo, 173-8610, Japan

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Haruki Kume

Department of Urology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan

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Published Online:16 May 2023https://doi.org/10.2217/imt-2023-0028

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Abstract

Aim: To validate a ‘drug score’ that stratifies patients receiving immunotherapy based on concomitant medications (antibiotics/proton pump inhibitors/corticosteroids) in urothelial carcinoma (UC). Materials & methods: We assessed oncological outcomes according to the drug score in 242 patients with advanced UC treated with pembrolizumab. Results: The drug score classified patients into three risk groups with significantly different survivals. Heterogeneous treatment effect analyses showed that the primary cancer site (bladder UC [BUC] or upper-tract UC [UTUC]) significantly affected the prognostic capability of the drug score; it significantly correlated with survivals in BUC, while there were no such correlations in UTUC. Conclusion: A drug score was examined in advanced UC treated with pembrolizumab and was validated in BUC but not in UTUC.

Plain language summary

Drug treatment for cancer may be weakened by other drugs. We checked whether some kinds of drugs really weakened the effect of drug treatment for cancer. We found that it was true for some kinds of cancer but not for other kinds.

Tweetable abstract

A concomitant drug-based score was validated in advanced urothelial cancer treated with pembrolizumab. It was validated in bladder cancer but not in upper-tract urothelial cancer.

Keywords:

Papers of special note have been highlighted as: • of interest; •• of considerable interest

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Vol. 15, No. 11

Supplemental Materials

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History

Received 5 February 2023

Accepted 28 April 2023

Published online 16 May 2023

Published in print August 2023

Information

Keywords

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.futuremedicine.com/doi/suppl/10.2217/imt-2023-0028

Author contributions

S Taguchi and T Kawai contributed to the conception, study design, analysis and interpretation of data, and drafted the first manuscript. S Buti and M Bersanelli contributed to the conception, study design and supervision, and revised the manuscript critically for important intellectual content. Y Uemura contributed to the analysis and interpretation of data. K Kishitani, J Miyakawa, K Sugimoto, Y Nakamura, F Niimi, T Kaneko, J Kamei, D Obinata, K Yamaguchi, S Kakutani, K Kanazawa, Y Sugihara, M Tokunaga, Y Akiyama, Y Yamada, Y Sato and D Yamada contributed to acquisition of data. Y Enomoto, H Nishimatsu, T Fujimura, H Fukuhara, T Nakagawa, S Takahashi and H Kume supervised the study, helped to draft the manuscript and were involved in revising it critically for important intellectual content. All authors read and approved the final manuscript.

Acknowledgments

The authors thank Y Ikemori from Nihon University for helping with data collection.

Financial & competing interests disclosure

S Buti received honoraria as a speaker at scientific events and advisory role from Bristol-Myers Squibb (BMS), Pfizer, MSD, Ipsen, AstraZeneca and Novartis, outside the present work. M Bersanelli received, outside the present work, institutional research funding from Roche S.p.A., Pfizer, Seqirus UK, Novartis, BMS, Astra Zeneca and Sanofi Genzyme; personal honoraria as a speaker at scientific events by BMS, MSD, Novartis, Astra Zeneca, Pierre Fabre and Pfizer; personal honoraria for advisory role by Ipsen, Novartis, BMS and Pfizer; and personal fees for copyright transfer by Sciclone Pharmaceuticals, Pierre-Fabre, MSD and Sanofi Genzyme. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

This study was approved by the Institutional Review Board of the Graduate School of Medicine and Faculty of Medicine, The University of Tokyo (approval no. 10565), as well as that of each participating institution. All methods were conducted in accordance with the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards. Given the retrospective nature of the study, the requirement for written informed consent was waived.

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