Response Rate to Chemotherapy After Immune Checkpoint Inhibition in Metastatic Urothelial Cancer

Immune checkpoint inhibitors (ICIs) are active in metastatic urothelial carcinoma (MUC). They have joined chemotherapy (CT) as a standard of care. Here, we investigate the activity of CT after progression on ICIs. Two cohorts of sequential patients with MUC were described (n=28). Cohort A received first-line ICIs followed by CT after progression. Cohort B received CT after failure of first-line platinum-based CT followed by ICIs. Response rate (RR) to CT was assessed using Response Evaluation Criteria in Solid Tumors (RECIST v1.1) by a designated radiologist. Best RR for cohort A was 64%. Two patients experienced clinical progression and died before the first radiographic assessment. RR for cohort B was 21%, which was significantly lower than that for cohort A. Progression of disease occurred in 43% of cohort B patients by the end of CT. These data suggest a lack of cross resistance between CT and ICIs in MUC. Therefore, the sequencing of these drugs is likely to be important to maximise outcomes. This is particularly true after first-line ICIs as subsequent CT has significant activity.

In this report, we studied the effect of chemotherapy in metastatic bladder cancer, which relapsed after immune checkpoint inhibitors. We found that the activity of chemotherapy was maintained despite previous exposure to immune therapy. This underlines the importance of sequencing these agents to maximise outcomes.

European urology. 2017 Sep 13 [Epub ahead of print]

Bernadett Szabados, Nick van Dijk, Yen Zhi Tang, Michiel S van der Heijden, Akhila Wimalasingham, Alfonso Gomez de Liano, Simon Chowdhury, Simon Hughes, Sarah Rudman, Mark Linch, Thomas Powles

Barts Cancer Institute, Queen Mary University of London, London, UK; Department of Urology, University of Munich, Klinikum Grosshadern, Germany., Netherlands Cancer Institute, Amsterdam, The Netherlands., Barts Cancer Institute, Queen Mary University of London, London, UK., Guys and St Thomas' Hospital, London, UK., University College London, London, UK., Barts Cancer Institute, Queen Mary University of London, London, UK. Electronic address: .