Anti-PD-L1 Antibody Shows Activity in Metastatic Urothelial Bladder Cancer
As reported in a letter to Nature by Powles et al, the anti–PD ligand-1 (PD-L1) antibody MPDL3280A has shown good activity in patients with metastatic urothelial bladder cancer in a phase I study. Outcomes were best in patients with PD-L1 immunohistochemistry (IHC) expression of 2 or 3 in tumor-infiltrating immune cells. On the basis of data from the study, the U.S. Food and Drug Administration granted MPDL3280A Breakthrough Therapy status for bladder cancer in May 2014.
Study Details
In the study, 68 patients received MPDL3280A at 15 mg/kg every 3 weeks, with treatment continuing for the earlier of 16 cycles or 1 year or until disease progression. Among 67 patients evaluable for efficacy, PD-L1 IHC expression scores for tumor-infiltrating immune cells were 0 in 12 (18%), 1 in 23 (34%), 2 in 20 (30%), 3 in 10 (15%), and unknown in 2 (3%). Overall, 93% had received previous cisplatin- or carboplatin-based chemotherapy, and 72% had received two or more previous systemic treatments.
Response Rates
Among patients with ≥ 6 weeks of follow-up, objective response rates were 43% (including complete response in 7%) among those with IHC 2/3 tumors and 11% among those with IHC 0/1 tumors. Among patients with IHC 2/3 tumors and ≥ 12 weeks of follow-up, the response rate was 52% (13/25). All but 1 of 17 responders had ongoing response and all continued on treatment at the time of data cutoff.
Median duration of response was not reached, with durations ranging from 0.1+ to 30.3+ weeks in patients with IHC 2/3 tumors and from 0.1+ to 6.0+ weeks in those with IHC 0/1 tumors. Response was associated with tumor-infiltrating immune cell IHC scores (P = .026) but not tumor cell IHC scores (P = .93).
Adverse Events
Treatment-related adverse events of any grade occurred in 57% of patients, with the most common being decreased appetite, fatigue, and nausea (12% each). Treatment-related grade 3 or 4 adverse events occurred in 4.4%, consisting of grade 3 asthenia, thrombocytopenia, and decreased phosphorus in one patient each. No immune-related toxicities were reported.
The investigators concluded: “Further investigation of MPDL3280A in [urothelial bladder cancer] is warranted, in multiple settings, including in patients who have failed or are intolerable towards initial chemotherapy. Clinical studies are enrolling patients to study MPDL3280A in bladder and other cancers.”
Thomas Powles, MD, of Barts Cancer Institute, Queen Mary University of London, is the corresponding author for the Nature article.
The work was supported by F. Hoffmann-La Roche Ltd. For full disclosures of the study authors, visit www.nature.com/nature.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
