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Early C-reactive protein kinetics predict survival of patients with advanced urothelial cancer treated with pembrolizumab

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Abstract

Objective

To assess the prognostic and predictive ability of early C-reactive protein (CRP) kinetics, dynamic changes in CRP levels, in patients with advanced urothelial cancer treated with pembrolizumab.

Patients and methods

We retrospectively evaluated 97 patients with advanced urothelial cancer treated with pembrolizumab in second-line or later settings. Patients were divided into three early CRP kinetics groups: non-elevated (baseline CRP < 5 mg/L), responder (baseline CRP ≥ 5 mg/L and CRP decreased below baseline at least once within 30 days), and non-responder (baseline CRP ≥ 5 mg/L and CRP never decreased to baseline within 30 days). Association between early CRP kinetics and pembrolizumab efficacy including objective response rate (ORR), disease control rate (DCR), and overall survival (OS) were evaluated.

Results

Based on early CRP kinetics, 40, 27, and 30 patients were classified as non-elevated, responder, and non-responder, respectively. ORR and DCR were 33% and 60% in non-elevated, 30% and 48% in responder, and 17% and 40% in non-responder; without a statistically significant difference. OS was significantly different among the non-elevated, responder, and non-responder groups (p < 0.01), with 1-year survival rates of 69%, 61%, and 31%, respectively. Early CRP kinetics could discriminate the OS of patients without objective response. Non-responder was an independent predictor for OS (HR 3.65, p < 0.01), as well as liver metastasis and ECOG PS ≥ 2.

Conclusion

Early CRP kinetics is associated with survival of advanced urothelial cancer patients treated with pembrolizumab and could be a potential biomarker for clinical benefit from immune checkpoint inhibitors.

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Abbreviations

CI:

Confidence interval

CR:

Complete response

CRP:

C-reactive protein

DCR:

Disease control rate

ICI:

Immune checkpoint inhibitor

iCPD:

Immune confirmed progressive disease

irAE:

Immune related adverse event

iUPD:

Immune undetermined progressive disease

LDH:

Lactate dehydrogenase

NLR:

Neutrophil to lymphocyte ratio

ORR:

Objective response rate

OS:

Overall survival

PD:

Progressive disease

PD-1:

Programmed cell death protein 1

PR:

Partial response

RECIST:

Response Evaluation Criteria in Solid Tumors

SD:

Stable disease

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Acknowledgements

We would like to thank Editage (www.editage.com) for English language editing.

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Authors and Affiliations

  1. Department of Urology, Tokyo Medical and Dental University Graduate School, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan

    Toshiki Kijima, Hina Yamamoto, Kazutaka Saito, Soichiro Yoshida, Minato Yokoyama, Yoh Matsuoka & Yasuhisa Fujii

  2. Department of Breast and Medical Oncology, National Cancer Center Hospital East, Kashiwa, Japan

    Shota Kusuhara & Nobuaki Matsubara

  3. Department of Urology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan

    Noboru Numao, Takeshi Yuasa & Junji Yonese

  4. Department of Urology, Saitama Cancer Center, Saitama, Japan

    Yasuyuki Sakai & Yukio Kageyama

  5. Department of Urology, National Cancer Center Hospital East, Kashiwa, Japan

    Hitoshi Masuda

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  1. Toshiki Kijima
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  2. Hina Yamamoto
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Correspondence to Kazutaka Saito.

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Conflicts of interest

Y.F. and N.M received honoraria for lectures from MSD K.K., a subsidiary of Merk & Co., Inc., Kenilworth, NJ, USA. All other authors declare no conflicts of interest.

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Kijima, T., Yamamoto, H., Saito, K. et al. Early C-reactive protein kinetics predict survival of patients with advanced urothelial cancer treated with pembrolizumab. Cancer Immunol Immunother 70, 657–665 (2021). https://doi.org/10.1007/s00262-020-02709-2

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