Immunotherapy and urothelial carcinoma: An overview and future prospectives.

Urothelial carcinoma (UC) is a common malignancy with a high mortality rate when metastatic. Traditionally, systemic therapy consisted in platinum-based regimens as first-line, with Taxanes or Vinflunine as further lines. Recently, checkpoint inhibitors (CPIs) immunotherapy has emerged as a new therapeutic option. We searched in Medline, Pubmed and ClinicalTrial.gov databases for the relevant literature, reviewing the results of published trials and the design of ongoing studies involving CPIs in UC. Strong evidence supports the use of CPIs after failure of Cisplatin-based chemotherapy, although no predictive parameter is available so far. Expression of Programmed-Death-1-Ligand has given conflicting results, and is currently indicated only for the selection of Cisplatin-ineligible patients who should receive CPIs. The therapeutic landscape of UC is rapidly changing due to the availability of CPIs. Neoadjuvant trials with CPIs and trials combining two CPIs are promising and will further expand the use of immunotherapy.

Pierantoni F ，Maruzzo M ，Gardi M ，Bezzon E ，Gardiman MP ，Porreca A ，Basso U ，Zagonel V ... -  《-》

Update of systemic immunotherapy for advanced urothelial carcinoma.

Until recently, therapeutic options for metastatic urothelial carcinoma (UC) were limited to cytotoxic chemotherapy. Cisplatin-based combination chemotherapy has proven benefit in the perioperative settings for muscle-invasive disease and for metastatic disease. A large proportion of patients is cisplatin-ineligible and limited to less effective chemotherapeutic options. However, treatment options have recently expanded with the development of systemic immunotherapy with checkpoint inhibitors (CPIs).Herein we review the clinical trial data supporting the use of CPIs in UC. We also describe ongoing clinical trials that are exploring CPIs in novel combinations and in a variety of disease settings. A comprehensive literature review was performed using Medline/Pubmed and clinical trials. Based on results of the IMvigor 210 clinical trial, the anti-programmed death-ligand1 antibody atezolizumab gained regulatory approval in May 2016 for use in locally advanced and metastatic UC in patients with progression of disease despite prior platinum-based chemotherapy. Since that time, additional CPIs (avelumab, durvalumab, nivolumab, and pembrolizumab) have gained regulatory approval in the postplatinum setting. The approval of pembrolizumab was supported by KEYNOTE-045, the first reported randomized, phase III trial of a CPI in UC. Atezolizumab and pembrolizumab are also approved for first-line therapy for cisplatin-ineligible patients with locally advanced or metastatic disease. The rapid expansion of therapeutic options in UC has shifted the treatment paradigm.

Gartrell BA ，He T ，Sharma J ，Sonpavde G ... -  《-》

From Clinical Trials to Real-life Clinical Practice: The Role of Immunotherapy with PD-1/PD-L1 Inhibitors in Advanced Urothelial Carcinoma.

A number of PD-1/PD-L1 inhibitors have recently been approved for use in patients with locally advanced or metastatic urothelial carcinoma (UC) on the basis of results from several clinical trials. To review the evidence from these trials and consider what it means for the use of these drugs in first-line and post-platinum settings in real-life clinical practice. PubMed was searched for full reports of clinical trials of single-agent PD-1/PD-L1 inhibitors in advanced UC. Twelve publications were included. Responses to PD-1/PD-L1 inhibitors appear to be durable but are only achieved in 17-26% of patients. These drugs offer different toxicity and efficacy profiles to standard chemotherapy regimens. This should be considered when choosing a treatment strategy for each patient. PD-1/PD-L1 inhibitors represent a major step forward in the management of advanced UC, although several questions remain regarding their optimal use in routine clinical practice. A validated predictive biomarker of response is yet to be defined, and this is perhaps the most significant unmet need for currently available drugs. We reviewed the results from clinical trials that investigated how well certain types of anticancer drugs called PD-1/PD-L1 inhibitors worked in patients with bladder cancer. We found that more research is required to identify (1) the factors that might predict which patients with bladder cancer will respond to PD-1/PD-L1 inhibitors and (2) the optimum duration of treatment with these drugs.

Hussain SA ，Birtle A ，Crabb S ，Huddart R ，Small D ，Summerhayes M ，Jones R ，Protheroe A ... -  《European Urology Oncology》

Immunotherapy for Urothelial Carcinoma: Current Evidence and Future Directions.

Tripathi A ，Plimack ER 《-》

[Immunotherapy in bladder cancer-quo vadis? Update on current trials and developments].

Todenhöfer T ，Boegemann M 《-》