Anti–PD-L1 Monoclonal Antibody MPDL3280A in Metastatic Urothelial Bladder Cancer
Treatments are limited for patients with metastatic urothelial bladder cancer. MPDL3280A is a human monoclonal antibody that is directed against the immune checkpoint receptor programmed death-1 (PD-1) ligand 1 (PD-L1), disrupting PD-L1 binding to its receptors PD-1 and B7.1. At ESMO 2014, investigators reported the results from a phase 1a study that evaluated the monoclonal antibody MPDL3280A 15 mg/kg intravenously every 3 weeks for up to 16 cycles in 74 patients with metastatic urothelial bladder cancer (Bellmunt J, et al. ESMO 2014: Abstract 808O).
The analysis of PD-L1 expression by immunohistochemistry (IHC) showed that PD-L1 IHC level 2/3 expression was observed in 33 patients and IHC level 0/1 expression was seen in 36 patients. In the IHC level 2/3 expression cohort, the overall response rate (ORR) was 52%, including 2 complete responses, and the median progression-free survival (PFS) was 24 weeks. For patients with IHC level 0/1 expression, the ORR was 14%, and all were partial responses; the median PFS was 8 weeks. Overall, 19 of the 22 responders still continued to respond at the time of this analysis. The median time to first response was 42 days for the 17 responders. The median duration of response was not reached in the PD-L1–positive patients (range, 0.1+ to 42+ weeks) or the PD-L1–negative patients (range, 6+ to 19+ weeks).
All grade treatment-related adverse events occurred in 65% of the patients. Common adverse events included fatigue (15%), decreased appetite (12%), and nausea (11%). Treatment-related grade 3 adverse events were reported in 5% of the patients, including asthenia, thrombocytopenia, and decreased blood phosphorus; no treatment-related grade 4 adverse events or deaths were observed. There were no discontinuations resulting from treatment-related adverse events.
Overall, these preliminary results for MPDL3280A monotherapy in patients with heavily pretreated urothelial bladder cancer indicate that this monoclonal antibody is well-tolerated in this patient population and leads to antitumor responses that correlate with PD-L1 status.