Viktoria Stühler1, Jan Moritz Maas1, Jonas Bochem2, Inês Anselmo da Costa1, Tilman Todenhöfer1, Arnulf Stenzl1, Jens Bedke3. 1. Department of Urology, Eberhard Karls University Tübingen, Hoppe-Seyler-Str. 3, 72076, Tübingen, Germany. 2. Department of Dermatology, Eberhard Karls University Tübingen, Tübingen, Germany. 3. Department of Urology, Eberhard Karls University Tübingen, Hoppe-Seyler-Str. 3, 72076, Tübingen, Germany. jens.bedke@med.uni-tuebingen.de.
Abstract
INTRODUCTION: The survival of patients with metastatic urothelial cancer (mUC) is poor. During the last 40 years, chemotherapy was the predominant treatment modality for mUC. The discovery of the immune checkpoint inhibitors (ICI), especially the inhibitors of the programmed cell death 1 and its ligand (PD-1/PD-L1), has revolutionized cancer immunotherapy. The PD-1 and PD-L1 inhibitors provide a new and effective treatment option for patients with UC, particularly for patients with recurrence after platinum-based therapy and those who are ineligible for cisplatin. METHODS: A literature search on PubMed, ClinicalTrials.gov and selected annual congress abstracts was conducted in May 2018, using a combination of keywords, medical subject headings (MeSH) terms and free text incorporating urothelial bladder cancer; immunotherapy; immune checkpoint inhibition, biomarkers, PD1/PD-L1. RESULTS: Although some patients demonstrate complete and/or durable responses under ICI, the reliable prediction of response to ICI is not possible. In the clinical setting, physicians are not able to predict response to ICI in mUC and to adequately select patients who will benefit. Exploratory analysis of clinical trial data revealed that PD-L1 expression, tumor mutation burden, tumor-infiltrating lymphocytes and gene expression profiles might have some predictive and/or prognostic value in different patient populations. CONCLUSION: Validated robust biomarkers are still needed to overcome this hurdle to forecast response of ICI in UC patients.
INTRODUCTION: The survival of patients with metastatic urothelial cancer (mUC) is poor. During the last 40 years, chemotherapy was the predominant treatment modality for mUC. The discovery of the immune checkpoint inhibitors (ICI), especially the inhibitors of the programmed cell death 1 and its ligand (PD-1/PD-L1), has revolutionized cancer immunotherapy. The PD-1 and PD-L1 inhibitors provide a new and effective treatment option for patients with UC, particularly for patients with recurrence after platinum-based therapy and those who are ineligible for cisplatin. METHODS: A literature search on PubMed, ClinicalTrials.gov and selected annual congress abstracts was conducted in May 2018, using a combination of keywords, medical subject headings (MeSH) terms and free text incorporating urothelial bladder cancer; immunotherapy; immune checkpoint inhibition, biomarkers, PD1/PD-L1. RESULTS: Although some patients demonstrate complete and/or durable responses under ICI, the reliable prediction of response to ICI is not possible. In the clinical setting, physicians are not able to predict response to ICI in mUC and to adequately select patients who will benefit. Exploratory analysis of clinical trial data revealed that PD-L1 expression, tumor mutation burden, tumor-infiltrating lymphocytes and gene expression profiles might have some predictive and/or prognostic value in different patient populations. CONCLUSION: Validated robust biomarkers are still needed to overcome this hurdle to forecast response of ICI in UC patients.
Entities:
Keywords:
Biomarkers; Checkpoint inhibition; Immunotherapy; PD1/PD-L1; Urothelial bladder cancer (UBC)
Authors: Padmanee Sharma; Yu Shen; Sijin Wen; Sachiko Yamada; Achim A Jungbluth; Sacha Gnjatic; Dean F Bajorin; Victor E Reuter; Harry Herr; Lloyd J Old; Eiichi Sato Journal: Proc Natl Acad Sci U S A Date: 2007-02-27 Impact factor: 11.205
Authors: J P Stein; G Lieskovsky; R Cote; S Groshen; A C Feng; S Boyd; E Skinner; B Bochner; D Thangathurai; M Mikhail; D Raghavan; D G Skinner Journal: J Clin Oncol Date: 2001-02-01 Impact factor: 44.544
Authors: D Kaufman; D Raghavan; M Carducci; E G Levine; B Murphy; J Aisner; T Kuzel; S Nicol; W Oh; W Stadler Journal: J Clin Oncol Date: 2000-05 Impact factor: 44.544
Authors: H von der Maase; S W Hansen; J T Roberts; L Dogliotti; T Oliver; M J Moore; I Bodrogi; P Albers; A Knuth; C M Lippert; P Kerbrat; P Sanchez Rovira; P Wersall; S P Cleall; D F Roychowdhury; I Tomlin; C M Visseren-Grul; P F Conte Journal: J Clin Oncol Date: 2000-09 Impact factor: 44.544
Authors: Woonyoung Choi; Sima Porten; Seungchan Kim; Daniel Willis; Elizabeth R Plimack; Jean Hoffman-Censits; Beat Roth; Tiewei Cheng; Mai Tran; I-Ling Lee; Jonathan Melquist; Jolanta Bondaruk; Tadeusz Majewski; Shizhen Zhang; Shanna Pretzsch; Keith Baggerly; Arlene Siefker-Radtke; Bogdan Czerniak; Colin P N Dinney; David J McConkey Journal: Cancer Cell Date: 2014-02-10 Impact factor: 31.743
Authors: Guillaume Ploussard; Shahrokh F Shariat; Alice Dragomir; Luis A Kluth; Evanguelos Xylinas; Alexandra Masson-Lecomte; Malte Rieken; Michael Rink; Kazumasa Matsumoto; Eiji Kikuchi; Tobias Klatte; Stephen A Boorjian; Yair Lotan; Florian Roghmann; Adrian S Fairey; Yves Fradet; Peter C Black; Ricardo Rendon; Jonathan Izawa; Wassim Kassouf Journal: Eur Urol Date: 2013-10-09 Impact factor: 20.096
Authors: Ivan de Kouchkovsky; Li Zhang; Errol J Philip; Francis Wright; Daniel M Kim; Divya Natesan; Daniel Kwon; Hansen Ho; Son Ho; Emily Chan; Sima P Porten; Anthony C Wong; Arpita Desai; Franklin W Huang; Jonathan Chou; David Y Oh; Raj S Pruthi; Lawrence Fong; Eric J Small; Terence W Friedlander; Vadim S Koshkin Journal: J Immunother Cancer Date: 2021-05 Impact factor: 13.751
Authors: Jens Bedke; Axel S Merseburger; Yohann Loriot; Daniel Castellano; Ernest Choy; Ignacio Duran; Jonathan E Rosenberg; Daniel P Petrylak; Robert Dreicer; Jose L Perez-Gracia; Jean H Hoffman-Censits; Michiel S Van Der Heijden; Julie Pavlova; Lars Thiebach; Sabine de Ducla; Simon Fear; Thomas Powles; Cora N Sternberg Journal: Eur Urol Focus Date: 2020-11-06