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 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 ... -  《-》

Emerging Role of Immunotherapy in Advanced Urothelial Carcinoma.

Koshkin VS ，Grivas P 《-》

Urothelial Carcinoma of the Bladder and the Rise of Immunotherapy.

With the advent of platinum-based chemotherapy, survival rates for metastatic urothelial carcinoma have plateaued, giving way to the modern immunotherapy paradigm. Although immunotherapy as an effective treatment dates back to the live, attenuated bacillus Calmette-Guérin vaccine, the recent impact of immune checkpoint inhibitors targeting programmed death/programmed death-ligand 1 (PD-1/PD-L1) coupled with the promise of both anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) antibodies and indoleamine-2, 3-dioxygenase-1 (IDO-1) inhibitors have provided a resurgence. To date, pembrolizumab, a PD-1 inhibitor, has been granted full FDA approval based on its high antitumor activity, tolerability, and efficacy, with notable prolonged durable responses in the second-line setting. Nivolumab (a PD-1 inhibitor) and atezolizumab, durvalumab, and avelumab (PD-L1 inhibitors) have also gained accelerated drug approval in the second-line setting. In addition, atezolizumab and pembrolizumab have been approved for platinum-ineligible patients in the first-line setting. Effective 2-drug combinations reported include nivolumab plus the CTLA-4 antibody ipilimumab and pembrolizumab plus the IDO-1 inhibitor epacadostat. Further expansion of immunotherapy will hinge in part on the ability to define responders versus nonresponders through the use of biomarkers like PD-L1 or mutational load. Clinical trials with immunotherapy for metastatic disease as single agents or in combination are ongoing. This review explores the rise of immunotherapy and presents the current treatments and challenges posed with development of biomarkers, and provides a summary of ongoing phase III clinical trials.

Chism DD 《-》