Response to Platinum Reintroduction After Immune Checkpoint Inhibitors for Metastatic Urothelial Carcinoma - Expert Commentary

Immune checkpoints inhibitors (ICIs) are approved as a second line of treatment for metastatic urothelial carcinoma (mUC) patients with progression on cisplatin-based chemotherapy. Chemotherapy is rarely reintroduced in these patients after the ICI.

A new study published by Gravis et al. in the European Journal of Cancer conducted a retrospective analysis to assess responses to the reintroduction of cisplatin-based chemotherapy after ICIs in mUC patients with progressive disease less than a year after the first-line platinum-based chemotherapy. The analysis included 12 patients from 4 centers. The authors found that the objective response rate (ORR) was 66.7% with eight out of the twelve patients responding. The median progression-free survival was 7.9 months, and the median survival was 11.2 months.

The biological mechanisms underlying the observed restoration of platinum sensitivity are unclear. The authors hypothesize that ICIs induce CD4+ T-cell activation improves cancer angiogenesis which in turns increases the diffusion of chemotherapy into the tumor and restores its chemosensitivity. If confirmed in additional series of patients, this interesting observation can inform the prospective testing of optimized ICI and chemotherapy sequencing strategies to improve clinical outcomes. 

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

Abstract Reference: 
Gravis G, French Genito-Urinary Tumor Group (GETUG) et al. Unexpected response to cisplatin rechallenge after immune checkpoint inhibitors in patients with metastatic urothelial carcinoma refractory to platinum regimen Eur J Cancer. 2018 Nov;104:236-238. doi: 10.1016/j.ejca.2018.09.002. Epub 2018 Oct 11.