Metastatic Bladder Ca

Guru Sonpavde

Apr 10, 2021

To summarize, this is a relatively young 59 yo female treated with neoadjuvant cisplatin/gemcitabine followed by radical cystectomy who progressed within a year with bone and lung metastases. Tumor PD-L1 expression is low. Given this is a second-line post-platinum progressive setting by conventional definition (since progressed within a year of last peri-op chemo), pembrolizumab alone is reasonable, since the phase III KEYNOTE045 trial did demonstrate benefit regardless of PD-L1 status. Tumor genomics should be obtained and if an activating FGFR3/2 mutation/fusion is found, erdafitinib is an option for the post-platinum progressive disease setting. The optimal sequencing of post-platinum erdafitinib and PD1/L1 inhibitors is unclear; contrasting data suggest PD1/L1 inhibitors may exhibit similar or lower activity in patients with somatic FGFR3/2 alterations (as opposed to those with wild type FGFR3/2). Enfortumab Vedotin is currently approved for third line therapy following platinum and PD1/L1 inhibitors. Sacituzumab Govitecan, a novel antibody drug conjugate is emerging and could become available for use in the clinic this year (awaiting regulatory review of phase II trial showing a response rate 27% in post-platinum and PD1/L1 inhibitors). Bone protective agents (denosumab or zoledronic acid) with calcium + vitamin D orally should be added unless there is a contraindication. Clinical trials should be considered a preferred option if available (combination VEGF + immune checkpoint inhibitors appear promising).