Immunotherapy Shows Potential in Advanced Bladder Cancer

Two phase 2 trials of multiple immunotherapies showed promising results in first- and second-line treatment of metastatic bladder cancer.

Findings from the KEYNOTE-052 and CheckMate 275 trial were presented at the European Society for Medical Oncology (ESMO) in Copenhagen.

In the KEYNOTE-052 trial, researchers evaluated the safety and efficacy of PD-1 blockade with pembrolizumab as first-line therapy in cisplatin ineligible patients with locally advanced or metastatic bladder cancer.

At the conference, researchers presented the preliminary analysis of the first 100 patients who were enrolled in the trial. The primary endpoint of the objective response was 24%.

To identify patients who were most likely to respond to the treatment, researchers defined the biomarker cut point as 10%, or greater total PD-L1 expression in tumor of immune cells. There were 30 participants who had this level of expression, of whom 11 responded to treatment.

Researchers found that in the KEYNOTE-052 trial, the treatment was well-tolerated. Currently, the median duration of response has not yet been reached.

“Pembrolizumab has substantial activity with a favorable safety profile as first-line therapy in cisplatin ineligible patients with metastatic bladder cancer,” said lead study author Arjun Balar. “The biomarker cut point will need to be validated in the larger study population, but seems to identify patients most likely to respond to pembrolizumab well. Immunotherapy is rapidly redefining our treatment approach for patients facing this dreadful disease.”

In patients suffering from metastatic bladder cancer, up to half are not eligible for survival prolonging first-line treatment with cisplatin-based chemotherapy, and available chemotherapy alternatives only gives these patients 9 to 10 months of survival.

Additionally, for several decades there had been no global standard-of-care for second-line therapy of metastatic bladder cancer patients who progress, despite platinum-based chemotherapy. That is, until the recent development of immune checkpoint blockade.

“There are insufficient treatment options for patients ineligible for cisplatin and for those progressing on cisplatin-based chemotherapy,” said researcher Maria De Santis. “This year the first immune checkpoint inhibitor, atezolizumab, was approved for patients with bladder cancer and CheckMate 275 provides similar results with nivolumab in the second-line setting.

“Immune checkpoint inhibitors have started to alter the therapeutic landscape for bladder cancer. We expect even more dramatic changes in the coming years with the use of immunotherapy in other clinical stages and as combination therapy.”

In the phase 2 CheckMate 275 trial, researchers assessed the safety and activity of the PD-1 inhibitor nivolumab. Included in the study were 270 metastatic bladder cancer patients who progressed despite first-line platinum-based chemotherapy.

There were 265 patients who could be evaluated for efficacy, of which, the primary endpoint of objective response rate was 19.6%. The median duration of response has not been reached at this time, with a median follow-up of 7 months.

In both patients who had tumors that expressed higher and lower levels of PD-L1, which included those with less than 1% of PD-L1, the objective response rate was above the rate achieved historically with chemotherapy.

The CheckMate 275 study of a PD-1 inhibitor in bladder is the largest to date.

“This data is being submitted to support registration of nivolumab for patients with metastatic urothelial cancer that has progressed despite platinum-based chemotherapy, an indication for which the US Food and Drug Administration has granted breakthrough therapy designation to nivolumab,” said lead study author Matthew Galsky. “Immune checkpoint blockade has become the most promising approach for these patients.”