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Effectiveness of pembrolizumab in trial-ineligible patients with metastatic urothelial carcinoma

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Abstract

Background

The KEYNOTE-045 trial showed that pembrolizumab therapy improved the survival of patients with advanced urothelial carcinoma (UC). However, its effectiveness in trial-ineligible patients remains unclear.

Materials and methods

We conducted a multicenter retrospective study to evaluate the effectiveness of pembrolizumab in patients with metastatic UC who were trial-ineligible. The data of 164 consecutive patients with platinum-treated metastatic UC who received pembrolizumab as second-line therapy were analyzed. Trial eligibility was assessed using the KEYNOTE-045 criteria. Inverse probability of treatment weighting (IPTW) was used to balance patient characteristics. Overall survival (OS) and progression-free survival (PFS) were examined using the IPTW-adjusted Kaplan–Meier method. IPTW-adjusted restricted mean survival times (RMSTs) were compared between ineligible and eligible patients.

Results

Seventy-five patients (45.7%) were classified as ineligible based on the KEYNOTE-045 criteria. Baseline hemoglobin concentration of less than 9.0 g/dL was the most common reason for trial protocol violation (N = 23 [14.0%]). An IPTW-adjusted logistic regression model showed that the trial-eligibility was not significantly associated with objective response (OR: 0.65, 95% CI: 0.32 to 1.29, P = 0.22). Ineligible patients had similar RMST for PFS (difference: 3.8 months, 95% CI: −1.6 to 9.3, P = 0.17) and RMST for OS (difference: 1.4 months, 95% CI: −5.4 to 8.2, P = 0.93) compared with eligible patients.

Conclusions

This study suggests that the effectiveness of pembrolizumab may be retained in ineligible patients with platinum-treated metastatic UC. Expanding trial eligibility criteria for these patients may be beneficial.

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Data availability

All data relevant to this retrospective study are included in the article.

Abbreviations

BMI:

Body mass index

CI:

Confidence interval

CPI:

Checkpoint inhibitor

ECOG:

Eastern cooperative oncology group

iCPD:

Immune-confirmed progressive disease

iCR:

Immune complete response

iPR:

Immune partial response

iSD:

Immune stable disease

iUPD:

Immune-unconfirmed progressive disease

IPTW:

Inverse probability of treatment weight

iRECIST:

Immunotherapy Response Evaluation Criteria in Solid Tumors

NLR:

Neutrophil-to-lymphocyte ratio

OR:

Odds ratio

OS:

Overall survival

PD-1:

Programmed cell death protein-1

PFS:

Progression-free survival

RMST:

Restricted mean survival time

SMD:

Standardized mean difference

trAE:

Treatment-related adverse event

UC:

Urothelial carcinoma

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Funding

The authors declare that no funds, grants, or other support were received during the preparation of this manuscript.

Author information

Authors and Affiliations

  1. Department of Urology, The Jikei University School of Medicine, 3-25-8 Nishi-shimbashi, Minato-ku, Tokyo, 105-8461, Japan

    Wataru Fukuokaya, Takafumi Yanagisawa, Masaki Hashimoto, Shutaro Yamamoto, Yuhei Koike, Yu Imai, Kosuke Iwatani, Hajime Onuma, Kagenori Ito, Fumihiko Urabe, Shunsuke Tsuzuki, Shoji Kimura, Jun Miki & Takahiro Kimura

  2. Department of Medical Oncology, Kameda Medical Center, 929 Higashi-cho, Kamogawa City, Chiba, 296-8602, Japan

    Yu Oyama

  3. Department of Urology, Kameda Medical Center, 929 Higashi-cho, Kamogawa City, Chiba, 296-8602, Japan

    Hirokazu Abe

Authors
  1. Wataru Fukuokaya
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  2. Takafumi Yanagisawa
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  3. Masaki Hashimoto
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  4. Shutaro Yamamoto
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  13. Jun Miki
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  14. Yu Oyama
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  15. Hirokazu Abe
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  16. Takahiro Kimura
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Contributions

Conception/design: WF, TK; collection and/or assembly of data: WF, TY, MH, SY, YK, YI, KI, HO, KI, FU, ST, SK, YO, and HA; data analysis and interpretation: WF, TY, YI, KI, HO, KI, FU, ST, SK, JM, YO, HA, and TK; manuscript writing: WF, TY, and TK; final approval of the manuscript: WF, TY, MH, SY, YK, YI, KI, HO, KI, FU, ST, SK, JM, YO, HA, and TK.

Corresponding author

Correspondence to Wataru Fukuokaya.

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Conflict of interest

The authors have no conflict of interests regarding this study.

Ethics approval

The study was approved by the Ethics Committee of The Jikei University School of Medicine for Biomedical Research and was conducted in accordance with Good Clinical Practice Guidelines and the Declaration of Helsinki.

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Fukuokaya, W., Yanagisawa, T., Hashimoto, M. et al. Effectiveness of pembrolizumab in trial-ineligible patients with metastatic urothelial carcinoma. Cancer Immunol Immunother 72, 841–849 (2023). https://doi.org/10.1007/s00262-022-03291-5

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  • DOI: https://doi.org/10.1007/s00262-022-03291-5

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