Immune checkpoint inhibitors for urothelial cancer: New hope with new options

Platinum-based chemotherapy has been the mainstay of treatment for urothelial cancer

Platinum-based chemotherapy has been the mainstay of treatment for urothelial cancer; however, targeted biologics are now gaining prominence in this setting. Programmed death-1 (PD-1/PD-L1) checkpoint inhibitors facilitate tumour infiltration by T cells, resulting in targeted destruction by the immune system.

Earlier this year, the PD-L1 inhibitor atezolizumab was approved by the US FDA for the treatment of locally advanced/metastatic urothelial cancer. Late-breaking results for other PD-1/PD-L1 inhibitors in urothelial cancer offer hope for the future treatment of metastatic urothelial cancer in the post-chemotherapy setting. 

Pembrolizumab has been investigated as a first-line treatment for metastatic urothelial cancer in 374 patients enrolled in the open-label phase II KEYNOTE-052 study as reported on Saturday by Dr Arjun Balar of the NYU Langone Medical Center, New York, USA (Abstract LBA32_PR). Preliminary results were very promising, with objective and complete response rates of 24% and 6%, respectively, in the overall population. Notably, in a subpopulation of 30 patients with combined tumour and immune cell PD-L1 expression of ≥10%—the cut-off point determined to identify those patients most likely to respond to pembrolizumab—11 patients (objective response rate 37%) responded to treatment. At a median 8-month follow-up, the median duration of response is yet to be reached in any patient subgroup in this study and toxicity was manageable.

The PD-1 inhibitor nivolumab is approved for the treatment of a number of advanced cancers. Results from CheckMate 275—to date, the largest phase II trial of nivolumab in locally advanced urothelial cancer—were presented on Saturday by Professor Matthew Galsky from Mount Sinai School of Medicine, New York, USA (Abstract LBA31_PR). While objective and complete responses were seen in 19.6% and 2.3%, respectively, of the 265 patients evaluated for efficacy, higher respective objective and complete response rates of 28.4% and 4.9% were reported in 81 patients with tumour cell PD-L1 expression of ≥5%. At a median follow-up of 7 months, the median duration of response had not been reached. Professor Galsky added that these data will now be used to support the US registration of nivolumab for the treatment of metastatic urothelial cancer after failure of platinum-based chemotherapy, an indication for which the US FDA has granted Breakthrough Therapy Designation. 

Commenting on his results, Dr Balar said, “These findings, together with results from a previous study with atezolizumab, suggest that in the very near future immunotherapy will become a potential standard of care in the first-line setting for these patients.”

This article appeared in the Tuesday edition of the Daily Reporter