Urothelial cancer of the bladder, renal pelvis, ureter, and other urinary organs is the fifth most common cancer in the United States, and systemic platinum-based chemotherapy remains the standard of care for first-line treatment of advanced/metastatic urothelial carcinoma (UC). Until recently, there were very limited options for patients who are refractory to chemotherapy, or do not tolerate chemotherapy due to toxicities and overall outcomes have remained very poor. While the role of immunotherapy was first established in non-muscle invasive bladder cancer in the 1970s, no systemic immunotherapy was approved for advanced disease until the recent approval of a programmed death ligand-1 (PD-L1) inhibitor, atezolizumab, in patients with advanced/metastatic UC who have progressed on platinum-containing regimens. This represents a significant milestone in this disease after a void of over 30 years. In addition to atezolizumab, a variety of checkpoint inhibitors have shown a significant activity in advanced/metastatic urothelial carcinoma and are expected to gain Food and Drug Administration (FDA) approval in the near future. The introduction of novel immunotherapy agents has led to rapid changes in the field of urothelial carcinoma. Numerous checkpoint inhibitors are being tested alone or in combination in the first and subsequent-line therapies of metastatic disease, as well as neoadjuvant and adjuvant settings. They are also being studied in combination with radiation therapy and for non-muscle invasive bladder cancer refractory to BCG. Furthermore, immunotherapy is being utilized for those ineligible for firstline platinum-based chemotherapy. This review outlines the novel immunotherapy agents which have either been approved, or are currently being investigated in clinical trials in UC.

Hemophagocytic lymphohistiocytosis (HLH) is a rare and life threatening disorder characterized by excessive immune activation with resulting tissue injury [1]. Ibrutinib is an irreversible inhibito...

495 Background: In the INTORSECT trial, not progression-free (PFS), but overall survival (OS) was higher with sorafenib vs. temsirolimus in 2^nd setting after 1^st sunitinib therapy. Here, we compare the PFS and OS between any vascular endothelial growth factor inhibitor (VEGF TKI) and mTOR inhibitors (mTORi) in 2^nd setting in mRCC after progression on 1^st VEGF TKI. Methods: Pts were identified from an institutional database. Survival estimates of PFS and OS were assessed from initiation of 2^nd therapy by Kaplan-Meier methodology and stratified by the median PFS of the 1^st therapy. Results: Of 142 pts, 66 received a VEGF TKI (n=24, 36%) or an mTORi (n=42, 64%) in 2^nd setting. Pts and disease characteristics with corresponding outcomes are presented in the table. Conclusions: A trend for improved PFS and OS was found with 2^nd therapy with a VEGF TKI over an mTORi. Longer OS with 2^nd VEGF TKI was seen in those on 1^st VEGF TKI <8 months suggesting that continued VEGF inhibition may be a reasonable strategy in these pts. Data need to be validated in a larger cohort. [Table: see text]