ESMO 2016: Anti-PD-1 Therapy for Cisplatin Ineligible Bladder Cancer Patients

New immunotherapies that target PD-1 are now showing promise for first-line and second-line treatment of metastatic bladder cancer, according to the latest results from two phase II trials presented at the European Society for Medical Oncology (ESMO) 2016 Congress, held Oct. 7-11, 2016, Copenhagen, Denmark.

Up to 50% of patients with metastatic bladder cancer are not eligible for first-line treatment with cisplatin-based chemotherapy. Survival in these patients is just 9 to 10 months with currently available alternative chemotherapy.  Now, two studies presented at this meeting are suggesting immune checkpoint inhibitors may alter the therapeutic landscape for this patient population.

The phase II KEYNOTE-052 trial 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. Pembrolizumab blocks the interaction between PD-1 and its ligands (PD-L1 and PD-L2).

Researchers presented (abstract LBA32_PR) the preliminary analysis of the first 100 patients enrolled in the trial. The primary endpoint of objective response rate was 24%. The biomarker cut-off 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 tumor cells. The researchers found that 30 patients had this level of expression and 11 patients (37%) responded to treatment. The median duration of response has not yet been reached as of October 8, 2016. The treatment was well-tolerated.

“Pembrolizumab has substantial activity with a favorable 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,” said lead study author Arjun Balar, MD, who is an Assistant Professor at NYU Langone Medical Center.

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 (abstract LBA31_PR) at this meeting, 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 had progressed despite first-line platinum-based chemotherapy.

In this particular study, 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. CheckMate 275 is the largest study of a PD-1 inhibitor in bladder cancer reported to date. The median duration of response has not yet been reached, with a median follow-up of 7 months.

Lead study author Matthew Galsky, MD, who is a Professor of Medicine, Mount Sinai School of Medicine, New York, said these data are being submitted to the US Food and Drug Administration (FDA) in the hopes that nivolumab can now be granted breakthrough therapy designation in this study population.