Anti-Programmed Cell Death 1/Ligand 1 (PD-1/PD-L1) Antibodies for the Treatment of Urothelial Carcinoma: State of the Art and Future Development

Thomas Powles, Andrea Necchi, Galit Rosen, Subramanian Hariharan, Andrea B Apolo

Research output: Contribution to journalReview article

Abstract

Immunotherapy with programmed cell death 1/ligand 1 (PD-1/PD-L1) checkpoint inhibitors has expanded a previously limited pool of effective treatment options for patients with metastatic urothelial carcinoma, particularly those with recurring or refractory disease and those who are ineligible for cisplatin. This review reports key findings from completed and ongoing clinical trials that highlight the potential of PD-1/PD-L1 blockade in urothelial carcinoma. A literature search was performed of PubMed, Embase, ClinicalTrials.gov, and selected annual congress abstracts. Prospective studies, reviews, editorials, and descriptions of ongoing anti-PD-1/PD-L1 studies in bladder cancer were included. Anti-PD-1/PD-L1 monoclonal antibodies have shown efficacy and safety across patient subgroups with urothelial carcinoma, including those with poor prognostic factors. Efficacy was similar across different anti-PD-1/PD-L1 agents. Although these antibodies have demonstrated durable responses in a subset of patients with urothelial carcinoma, clinicians are currently unable to predict which patients may derive benefit from immune checkpoint blockade. Anti-PD-1/PD-L1 antibodies have shown favorable clinical activity and tolerability in patients with metastatic urothelial carcinoma refractory to platinum-based therapy or who are ineligible for cisplatin. The activity of PD-1/PD-L1 inhibitors is now also being studied as first-line monotherapy in cisplatin-eligible patients in combination with chemotherapy as maintenance therapy after first-line chemotherapy, and in earlier disease states, such as muscle-invasive and non-muscle-invasive bladder cancer. Better predictive tools to define target patient populations are needed, as are further investigations to define optimal combinations or sequencing of treatments.

Original languageEnglish
Pages (from-to)117-129
Number of pages13
JournalClinical Genitourinary Cancer
Volume16
Issue number2
DOIs
Publication statusPublished - Apr 2018

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CD274 Antigen
Carcinoma
Antibodies
Cisplatin
Urinary Bladder Neoplasms
Therapeutics
Health Services Needs and Demand
Patient Safety
Combination Drug Therapy
Platinum
PubMed
Immunotherapy
Monoclonal Antibodies
Clinical Trials
Prospective Studies
Drug Therapy
Muscles

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Anti-Programmed Cell Death 1/Ligand 1 (PD-1/PD-L1) Antibodies for the Treatment of Urothelial Carcinoma : State of the Art and Future Development. / Powles, Thomas; Necchi, Andrea; Rosen, Galit; Hariharan, Subramanian; Apolo, Andrea B.

In: Clinical Genitourinary Cancer, Vol. 16, No. 2, 04.2018, p. 117-129.

Research output: Contribution to journalReview article

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abstract = "Immunotherapy with programmed cell death 1/ligand 1 (PD-1/PD-L1) checkpoint inhibitors has expanded a previously limited pool of effective treatment options for patients with metastatic urothelial carcinoma, particularly those with recurring or refractory disease and those who are ineligible for cisplatin. This review reports key findings from completed and ongoing clinical trials that highlight the potential of PD-1/PD-L1 blockade in urothelial carcinoma. A literature search was performed of PubMed, Embase, ClinicalTrials.gov, and selected annual congress abstracts. Prospective studies, reviews, editorials, and descriptions of ongoing anti-PD-1/PD-L1 studies in bladder cancer were included. Anti-PD-1/PD-L1 monoclonal antibodies have shown efficacy and safety across patient subgroups with urothelial carcinoma, including those with poor prognostic factors. Efficacy was similar across different anti-PD-1/PD-L1 agents. Although these antibodies have demonstrated durable responses in a subset of patients with urothelial carcinoma, clinicians are currently unable to predict which patients may derive benefit from immune checkpoint blockade. Anti-PD-1/PD-L1 antibodies have shown favorable clinical activity and tolerability in patients with metastatic urothelial carcinoma refractory to platinum-based therapy or who are ineligible for cisplatin. The activity of PD-1/PD-L1 inhibitors is now also being studied as first-line monotherapy in cisplatin-eligible patients in combination with chemotherapy as maintenance therapy after first-line chemotherapy, and in earlier disease states, such as muscle-invasive and non-muscle-invasive bladder cancer. Better predictive tools to define target patient populations are needed, as are further investigations to define optimal combinations or sequencing of treatments.",
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