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International Journal of Clinical Oncology

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01-05-2020 | Urothelial Cancer | Original Article

Prognostic outcomes and safety in patients treated with pembrolizumab for advanced urothelial carcinoma: experience in real-world clinical practice

Authors: Daichi Tamura, Noriaki Jinnouchi, Masakazu Abe, Daiki Ikarashi, Tomohiko Matsuura, Renpei Kato, Shigekatsu Maekawa, Yoichiro Kato, Mitsugu Kanehira, Ryo Takata, Wataru Obara

Published in: International Journal of Clinical Oncology | Issue 5/2020

Abstract

Background

Prognostic outcomes and safety following treatment with pembrolizumab in patients with advanced urothelial carcinoma (UC) have not been fully elucidated in clinical practice. The aim of this study was to evaluate the oncological efficacy and safety of pembrolizumab after failure of platinum-based chemotherapy in Japanese patients with advanced UC in a routine clinical setting.

Methods

This retrospective study included 41 consecutive Japanese patients with advanced UC treated with pembrolizumab as second-line or greater therapy at Iwate Medical University Hospital from January 2018 to April 2019.

Results

The mean follow-up period was 6.2 months. The objective response rate, median progression-free survival, and median overall survival were 15%, 2.5 months, and 11.9 months, respectively. Univariate analysis identified poor performance status (> 1), liver metastasis, two or more metastatic organs, low hemoglobin levels, two or more prior regimens, high baseline C-reactive protein levels, higher relative C-reactive protein level change after 6 weeks, and higher relative neutrophil-to-lymphocyte ratio change after 6 weeks as significant predictors of overall survival. Among these factors, poor performance status (> 1), two or more metastatic organs, and higher relative neutrophil-to-lymphocyte ratio change after 6 weeks were identified as independent predictors of overall survival in multivariate analysis.

Conclusions

The introduction of pembrolizumab can result in favorable cancer control outcomes in Japanese patients with advanced UC, and the prognosis of these patients can be stratified according to three potential parameters, including poor performance status, high number of metastatic organs, and higher relative neutrophil-to-lymphocyte ratio change.

Torre LA, Bray F, Siegel RL et al (2015) Global cancer statistics, 2012. CA Cancer J Clin 65:87–108CrossRef

Seront E, Machiels JP (2015) Molecular biology and targeted therapies for urothelial carcinoma. Cancer Treat Rev 41:341–353CrossRef

Bellmunt J, de Wit R, Vaughn DJ et al (2017) Pembrolizumab as second-line therapy for advanced urothelial carcinoma. N Engl J Med 376:1015–1026CrossRef

Hanahan D, Weinberg RA (2011) Hallmarks of cancer: the next generation. Cell 144:646–674CrossRef

Selders GS, Fetz AE, Radic MZ et al (2017) An overview of the role of neutrophils in innate immunity, inflammation and host-biomaterial integration. Regen Biomater 4:55–68CrossRef

Smith JA (1994) Neutrophils, host defense, and inflammation: a double-edged sword. J Leukoc Biol 56:672–686CrossRef

Petrie HT, Klassen LW, Kay HD (1985) Inhibition of human cytotoxic T lymphocyte activity in vitro by autologous peripheral blood granulocytes. J Immunol 134:230–234

Diakos CI, Charles KA, McMillan DC et al (2014) Cancer-related inflammation and treatment effectiveness. Lancet Oncol 15:493–503CrossRef

Heppt MV, Heinzerling L, Kähler KC et al (2017) Prognostic factors and outcomes in metastatic uveal melanoma treated with programmed cell death-1 or combined PD-1/cytotoxic T-lymphocyte antigen-4 inhibition. Eur J Cancer 82:56–65CrossRef

10.

Sacdalan DB, Lucero JA, Sacdalan DL (2018) Prognostic utility of baseline neutrophil-to-lymphocyte ratio in patients receiving immune checkpoint inhibitors: a review and meta-analysis. Onco Targets Ther 11:955–965CrossRef

11.

Capone M, Giannarelli D, Mallardo D et al (2018) Baseline neutrophil-to-lymphocyte ratio (NLR) and derived NLR could predict overall survival in patients with advanced melanoma treated with nivolumab. J Immunother Cancer 6:74CrossRef

12.

Tamiya M, Tamiya A, Hosoya K et al (2019) Efficacy and safety of pembrolizumab as first-line therapy in advanced non-small cell lung cancer with at least 50% PD-L1 positivity: a multicenter retrospective cohort study (HOPE-001). Investig New Drugs. https://doi.org/10.1007/s10637-019-00843-y(in press) CrossRef

13.

Li X, Ma X, Tang L et al (2016) Prognostic value of neutrophil-to-lymphocyte ratio in urothelial carcinoma of the upper urinary tract and bladder: a systematic review and meta-analysis. Oncotarget 8:62681–62692PubMedPubMedCentral

14.

Kim HS, Ku JH (2016) Systemic inflammatory response based on neutrophil-to-lymphocyte ratio as a prognostic marker in bladder cancer. Dis Markers. https://doi.org/10.1155/2016/8345286(in press) CrossRefPubMedPubMedCentral

15.

Tanaka N, Kikuchi E, Shirotake S et al (2014) The predictive value of C-reactive protein for prognosis in patients with upper tract urothelial carcinoma treated with radical nephroureterectomy: a multi-institutional study. Eur Urol 65:227–234CrossRef

16.

Suh KJ, Kim SH, Kim YJ et al (2018) Post-treatment neutrophil-to-lymphocyte ratio at week 6 is prognostic in patients with advanced non-small cell lung cancers treated with anti-PD-1 antibody. Cancer Immunol Immunother 67:459–470CrossRef

17.

Eisenhauer EA, Therasse P, Bogaerts J et al (2009) New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 45:228–247CrossRef

18.

National Cancer Institute (2010) Common terminology criteria for adverse events (CTCAE) version 4.0. Available via DIALOG. https://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.03/CTCAE_4.03_2010-06-14_QuickReference_5x7.pdf. Accessed Aug 2019

19.

Bellmunt J, Choueiri TK, Fougeray R et al (2010) Prognostic factors in patients with advanced transitional cell carcinoma of the urothelial tract experiencing treatment failure with platinum-containing regimens. J Clin Oncol 28:1850–1855CrossRef

20.

Sonpavde G, Pond GR, Fougeray R et al (2013) Time from prior chemotherapy enhances prognostic risk grouping in the second-line setting of advanced urothelial carcinoma: a retrospective analysis of pooled, prospective phase 2 trials. Eur Urol 63:717–723CrossRef

21.

Joseph RW, Elassaiss-Schaap J, Kefford R et al (2018) Baseline tumor size is an independent prognostic factor for overall survival in patients with melanoma treated with pembrolizumab. Clin Cancer Res 24:4960–4967CrossRef

22.

Katsurada M, Nagano T, Tachihara M et al (2019) Baseline tumor size as a predictive and prognostic factor of immune checkpoint inhibitor therapy for non-small cell lung cancer. Anticancer Res 39:815–825CrossRef

23.

Gao GD, Sun B, Wang XB et al (2017) Neutrophil to lymphocyte ratio as prognostic indicator for patients with esophageal squamous cell cancer. Int J Biol Markers 32:409–414CrossRef

24.

Marchioni M, Primiceri G, Ingrosso M et al (2016) The clinical use of the neutrophil to lymphocyte ratio (NLR) in urothelial cancer: a systematic review. Clin Genitourin Cancer 14:473–484CrossRef

25.

Yasuoka S, Yuasa T, Nishimura N et al (2019) Initial experience of pembrolizumab therapy in japanese patients with metastatic urothelial cancer. Anticancer Res 39:3887–3892CrossRef

26.

Lalani AA, Xie W, Martini DJ et al (2018) Change in neutrophil-to-lymphocyte ratio (NLR) in response to immune checkpoint blockade for metastatic renal cell carcinoma. J Immunother Cancer 6:5CrossRef

27.

Dusselier M, Deluche E, Delacourt N et al (2019) Neutrophil-to-lymphocyte ratio evolution is an independent predictor of early progression of second-line nivolumab-treated patients with advanced non-small-cell lung cancers. PLoS ONE 14:e0219060CrossRef

28.

Passiglia F, Galvano A, Castiglia M et al (2019) Monitoring blood biomarkers to predict nivolumab effectiveness in NSCLC patients. Ther Adv Med Oncol 11:1758835919839928CrossRef

29.

de Velasco G, Krajewski KM, Albiges L et al (2016) Radiologic heterogeneity in responses to anti-PD-1/PD-L1 therapy in metastatic renal cell carcinoma. Cancer Immunol Res 4:12–17CrossRef

Title: Prognostic outcomes and safety in patients treated with pembrolizumab for advanced urothelial carcinoma: experience in real-world clinical practice
Authors: Daichi Tamura
Noriaki Jinnouchi
Masakazu Abe
Daiki Ikarashi
Tomohiko Matsuura
Renpei Kato
Shigekatsu Maekawa
Yoichiro Kato
Mitsugu Kanehira
Ryo Takata
Wataru Obara
Publication date: 01-05-2020
Publisher: Springer Singapore
Keywords: Urothelial Cancer
Urothelial Cancer
Cytostatic Therapy
Published in: International Journal of Clinical Oncology / Issue 5/2020
Print ISSN: 1341-9625
Electronic ISSN: 1437-7772
DOI: https://doi.org/10.1007/s10147-019-01613-9

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