Immunotherapy shows positive results in metastatic bladder cancer treatment

Immunotherapy has shown promising results in the first and

second line treatment of metastatic bladder cancer in two phase trials, a recent research

suggests.

Up to half of the patients with metastatic bladder cancer are not eligible for survival

prolonging first line treatment with cisplatin-based chemotherapy.

Survival in these patients is just nine to ten months with currently available alternative

chemotherapy.

The phase II KEYNOTE-052 trial1 evaluated the efficacy and safety of PD-1 blockade with

pembrolizumab as first line therapy in cisplatin ineligible patients with metastatic or locally

advanced bladder cancer.

The researchers presented the preliminary analysis of the first 100 patients enrolled in the

trial.

The primary endpoint of objective response rate was 24 percent.

The biomarker cut point to identify the patients, who are most likely to respond to the drug

was determined to be 10 percent or greater total PD-L1 expression in immune cells or tumor

cells.

Thirty patients had this level of expression of whom 11 (37 percent) responded to treatment.

The median duration of response has not yet been reached and treatment was well tolerated.

Lead author Arjun Balar, said: "Pembrolizumab has substantial activity with a favourable safety

profile as first line therapy in cisplatin ineligible patients with metastatic bladder cancer.

"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," he added.

For several decades, there had been no global standard of care for second line treatment of

patients with metastatic bladder cancer who progress despite platinum-based chemotherapy until

the recent development of immune checkpoint blockade.

In another study, the phase II CheckMate 275 trial2 assessed the activity and safety of the

PD-1 inhibitor nivolumab in 270 patients with metastatic bladder cancer who have progressed

despite first line platinum-based chemotherapy.

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

In the 265 patients who could be evaluated for efficacy, the primary endpoint of objective

response rate was 19.6 percent.

The median duration of response has not yet been reached, with a median follow-up of seven

months.

In both patients with tumors expressing higher and lower levels of PD-L1 (including those with

less than 1 percent PD-L1), the objective response rate was above that achieved historically

with chemotherapy.

"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 author Professor Matthew Galsky.

"Immune checkpoint blockade has become the most promising approach for these patients," he

added.

Commenting on the current management of bladder cancer, Maria De Santis, said, "There are

insufficient treatment options for patients ineligible for cisplatin and for those progressing

on cisplatin-based chemotherapy."

"This year the first immune check point inhibitor, atezolizumab, was approved for patients with

bladder cancer and CheckMate 275 provides similar results with nivolumab in the second line

setting," she said.

"KEYNOTE-052 confirms that immunotherapy is also active as first line therapy in cisplatin

ineligible patients, with a slightly lower response rate than chemotherapy. However, the

duration of response with pembrolizumab seems to exceed that of chemotherapy in historical

controls. The protocol included a new biomarker definition and cut-off which needs further

evaluation," said De Santis.

She concluded: "Immune check point 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."

The study is presented in ESMO 2016.