WashingtonD.C. [USA], Oct. 9 (ANI
): Immunotherapy has shown promising results in the first and
second line treatment of metastatic bladder cancer in two phase trials, a recent research
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
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
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
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
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
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
"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
Commenting on the current management of bladder cancer, Maria De Santis, said, "There are
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. (ANI