The Evolution of Immune Checkpoint Inhibitors in Advanced Urothelial Carcinoma

Abstract

Urothelial carcinoma is an aggressive cancer and development of metastases remains a challenge for clinicians. Immune checkpoint inhibitors (ICIs) are significantly improving the outcomes of patients with metastatic urothelial cancer (mUC). These agents were first used in monotherapy after failure of platinum-based chemotherapy, but different strategies explored the optimal use of ICIs in a first-line metastatic setting. The “maintenance” strategy consists of the introduction of ICIs in patients who experienced benefit from first-line chemotherapy in a metastatic setting. This allows an earlier use of ICIs, without waiting for disease progression. We review the optimal management of mUC in the era of ICIs, based on the key clinical messages arising from the pivotal trials.

The Association between a Decrease in On-Treatment Neutrophil-to-Eosinophil Ratio (NER) at Week 6 after Ipilimumab Plus Nivolumab Initiation and Improved Clinical Outcomes in Metastatic Renal Cell Carcinoma

“…Immune checkpoint inhibitors (ICIs) targeting program-cell death 1 or its ligand (anti-PD1/anti-PDL1) and cytotoxic T-lymphocyte associated protein 4 (anti-CTLA-4) have revolutionized the treatment paradigm for multiple cancers and have brought unprecedented deep and durable treatment efficacy to patients with metastatic disease [ 1 , 2 , 3 , 4 , 5 ]. Kidney cancer is one of the leading examples demonstrating how immune checkpoint inhibitors enable sustained long-term overall survival in metastatic disease: after a minimal 5-year follow-up of the CheckMate 214 trial [ 6 ], almost 50% of the ipilimumab/nivolumab treated metastatic clear cell renal cell carcinoma (mccRCC) patients were still alive, with a median overall survival of 56 months, compared to that of 38 months in the sunitinib arm among the intention-to-treatment population.…”

A phase II study of retifanlimab, a humanized anti-PD-1 monoclonal antibody, in patients with solid tumors (POD1UM-203)

“…The development of checkpoint inhibitors, including monoclonal antibodies against cytotoxic T-lymphocyte-associated protein 4, programmed cell death protein-1 (PD-1), and programmed death-ligand 1 (PD-L1), has revolutionized the treatment of a wide range of cancers. 1 , 2 Immune checkpoint inhibitors, including PD-(L)1 inhibitors, either as monotherapy or in combination with other anticancer therapies, have shown high levels of efficacy and become standard of care for a number of solid tumor types, including melanoma, 3 non-small-cell lung cancer (NSCLC), 4 urothelial carcinoma, 5 and renal cell carcinoma (RCC). 6 …”

Cutoff values of PD‐L1 expression in urinary cytology samples for predicting response to immune checkpoint inhibitor therapy in upper urinary tract urothelial carcinoma

“…In recent years, as a result of an improved understanding of cancer immunobiology, systemic immunotherapies targeting immune checkpoint inhibitors (ICIs) have been explored and clinically applied for the treatment of urothelial carcinoma. 11 According to the results of several current clinical trials, PD-L1 expression is a biomarker that can indicate which patients will benefit the most from PD-1/PD-L1 −targeted therapies. 12,13 Several studies have demonstrated that PD-L1 expression can be evaluated in resection specimens and tissue microarray of UTUC, and have suggested that PD-L1 expression is associated with adverse pathological features and is an independent predictor of worse cancer-specific and overall survival.…”

“…In recent years, as a result of an improved understanding of cancer immunobiology, systemic immunotherapies targeting immune checkpoint inhibitors (ICIs) have been explored and clinically applied for the treatment of urothelial carcinoma 11 . According to the results of several current clinical trials, PD‐L1 expression is a biomarker that can indicate which patients will benefit the most from PD‐1/PD‐L1−targeted therapies 12,13 .…”