Anti-PD-L1 Drug Shows Promise in Bladder Cancer

December 10, 2014

A large phase I study showed that the PD-L1 antibody known as MPDL3280A has promising activity in patients with urothelial bladder cancer.

A large phase I study showed that the PD-L1 antibody known as MPDL3280A has promising activity in patients with urothelial bladder cancer (UBC), particularly in those with high expression of PD-L1 tumor-infiltrating immune cells.

“There have been no major advances for the treatment of metastatic UBC in the last 30 years,” wrote researchers led by Thomas Powles, MD, of Barts Cancer Institute at Queen Mary University in London. Chemotherapy remains the standard of care in these patients, and outcomes are generally poor. An interesting hallmark of UBC is a high rate of somatic mutations, which could aid in an immune response that would recognize tumor cells as foreign; expression of PD-L1, though, limits that response. Thus, the anti-PD-L1 drug was considered as an option, results of this phase I expansion study were published online ahead of print in Nature.

The study included 68 patients with safety data, and 67 available for efficacy evaluation. It began only with patients with PD-L1-positive immunohistochemistry (IHC), but was then expanded to include any PD-L1 status to see if others respond to the drug. Of the efficacy-evaluable patients, 18% had tumors ranked as IHC 0 in terms of PD-L1 expression, 34% were ranked as IHC 1, 30% as IHC 2, 15% as IHC 3, and 3% as unknown.

For patients with IHC 2/3 tumors, the objective response rate (ORR) to MPDL3280A was 43%. In sharp contrast, the ORR was only 11% in those with IHC 0/1 tumors. Two of the IHC 2/3 responses (7%) were complete responses. Specifically among the IHC 2/3 tumors with at least 12 weeks of follow-up, the ORR was 52%. “Sixteen of the seventeen responders had ongoing responses, and all seventeen responders continued on treatment with MPDL3280A at the data cutoff,” the researchers wrote. The median duration of response had not yet been reached.

The researchers also noted that responses were generally rapid, occurring at a median of 42 days from the start of treatment.

“There is an urgent need for efficacious and well-tolerated therapies in metastatic UBC, as even first-line chemotherapy is poorly tolerated in a large proportion of individuals,” the authors wrote. “The study results presented here demonstrate that not only can MPDL3280A treatment achieve high response rates, but also that the likelihood of response can be increased by determining the PD-L1 status of tumor-infiltrating immune cells.”

The drug was granted breakthrough designation by the US Food and Drug Administration earlier this year. Trials in several malignancies are now ongoing, including a phase II study in untreated advanced renal cell carcinoma and a randomized phase III trial in locally advanced or metastatic non-small-cell lung cancer.