Efficacy and Safety of Neoadjuvant Pembrolizumab in Patients with Muscle-Invasive Bladder Cancer - Expert Commentary

Neoadjuvant chemotherapy followed by radical cystectomy (RC) with lymph node dissection is the standard of care in patients with muscle-invasive urothelial bladder carcinoma (MIBC). Unfortunately, many patients are ineligible or unwilling to receive cisplatin-based neoadjuvant chemotherapy.

A new study published by Necchi et al. in the Journal of Clinical Oncology evaluated the efficacy and safety of Pembrolizumab as neoadjuvant therapy before RC in MIBC patients. The investigators enrolled fifty patients who were treated at two centers in Milan, Italy. Of these, 27 patients (54%) had cT3 tumor, 21 (42%) cT2 tumor, and two (4%) cT2-3N1 tumor. Patients received Pembrolizumab 200mg intravenously every three weeks for three cycles, followed by restaging before RC.

Twenty one patients achieved  pT0 (42%; 95% CI, 28.2% to 56.8%), 3 patients had pTa, 2 patients with pTis and 1 patient with pT1. 27 patients had down-staging to pT < 2 (54%; 95% CI, 39.3% to 68.2%).  Patients with a high CPS score had higher rates of  pT0. The most common adverse event was thyroid dysfunction. A biomarker analysis showed that 26 patients (52%) had deleterious DNA damage response and repair (DDR) and/or RB1 gene alterations. These patients also had a higher median tumor mutational burden (TMB). Interestingly, post-pembrolizumab TMB was significantly lower compared with the baseline TMB score. It is not clear whether these TMB estimates were adjusted for the clonality and tumor purity across different samples.

This important study highlights the potential for moving immune checkpoint inhibition to earlier stages of the treatment of bladder cancer patients. Combinations of immune checkpoints with chemotherapy and radiotherapy are currently being tested as definitive therapy for locally advanced muscle-invasive bladder cancer.


Written by: Bishoy M. Faltas, MD, Director of Bladder Cancer Research, Englander Institute for Precision Medicine, Weill Cornell Medicine

Abstract Reference: 
Necchi A. et al. Pembrolizumab as Neoadjuvant Therapy Before Radical Cystectomy in Patients With Muscle-Invasive Urothelial Bladder Carcinoma (PURE-01): An Open-Label, Single-Arm, Phase II Study. J Clin Oncol. 2018 Oct 20:JCO1801148. doi:10.1200/JCO.18.01148.


email news signup