Immunotherapy has shown promising results in first and second line treatment of metastatic bladder cancer in two phase II trials presented at the ESMO ( European Society for Medical Oncology ) Congress in Copenhagen.
Up to half of 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 trial has evaluated the efficacy and safety of PD-1 blockade with Pembrolizumab ( Keytruda ) as first line therapy in Cisplatin ineligible patients with metastatic or locally advanced bladder cancer.
Researchers have presented the preliminary analysis of the first 100 patients enrolled in the trial.
The primary endpoint of objective response rate was 24%.
The biomarker cut point to identify patients who are most likely to respond to the drug was determined to be 10% or greater total PD-L1 expression in immune cells or tumour cells.
Thirty patients had this level of expression of whom 11 ( 37% ) responded to treatment.
The median duration of response has not yet been reached and treatment was well tolerated.
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 the treatment approach for patients facing this dreadful disease.
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 presented, the phase II CheckMate 275 trial assessed the activity and safety of the PD-1 inhibitor Nivolumab ( Opdivo ) 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%.
The median duration of response has not yet been reached, with a median follow-up of seven months.
In both patients with tumours expressing higher and lower levels of PD-L1 ( including those with less than 1% PD-L1 ), the objective response rate was above that achieved historically with chemotherapy.
Source: NYU Langone Medical Centre, New York, 2016