Investigational Immunotherapy Demonstrates Response in Patients With PD-L1–Positive Metastatic Bladder Cancer

Get Permission

Thomas Powles, MD

Daniel P. Petrylak, MD

Sandra Horning, MD

[The study results] point to a new era in cancer treatment for a disease that has not seen a major advancement since the introduction of cisplatin-based combination chemotherapy in the 1980s.

—Daniel P. Petrylak, MD

The investigational immunotherapy agent MPDL3280A (also known as anti-PDL1) produced an overall response rate of 43% in a phase I study of patients previously treated for metastatic urothelial bladder cancer whose tumors were characterized as programmed death ligand 1 (PD-L1)-positive. Results of the study were presented at the 2014 ASCO Annual Meeting by Thomas Powles, MD, Clinical Professor of Genitourinary Oncology, Barts Cancer Institute at the Queen Mary University of London, United Kingdom.1 Daniel P. Petrylak, MD, Professor of Medicine and Urology at Yale Cancer Center and Yale School of Medicine, was the senior author of the study.

The anti–PD-L1 agent ­MPDL3280A is an investigational monoclonal antibody designed to interfere with the PD‑L1 protein. MPDL3280A is designed to target PD-L1 expressed on tumor cells and tumor-infiltrating immune cells, preventing it from binding to PD-1 and B7.1 on the surface of T cells. By inhibiting PD-L1, ­MPDL3280A may enable the activation of T cells, restoring their ability to effectively detect and kill tunor cells.

Study Details and Results

Dr. Powles presented results from the phase I single-arm, multicenter, open-label trial, which included a cohort of 68 people with previously treated, meta­static bladder cancer.  Thirty patients were identified as having tumors positive for PD-L1 (immunohistochemistry [IHC] 2/3) using an investigational PD-L1 diagnostic test being developed by Roche. Patients received 15 mg/kg of MPDL3280A intravenously every 3 weeks for up to 1 year.

After 6 weeks of follow-up, the objective response rate for the entire study population (both PD-L1–positive and PD-L1–negative), as measured by RECIST criteria was 43% (13/30). After 12 weeks, the objective response rate was 52% (13/25) in people with PD-L1–positive tumors.  A complete response (no radiographic evidence of tumor) was observed in 7% of patients with PD-L1–positive tumors (2/30).

The objective response rate was 11% (4/35) in people whose tumors were identified as PD-L1–negative (IHC 0/1) by the investigational test. The median time to response was 42 days.

Safety and Toxicity

Treatment-related grade 3 adverse events occurred in 4% (3/68) of people in the study. These included asthenia in 2%, thrombocytopenia in 2%, and blood phosphorus decrease in 2%). The most common adverse events observed to date occurring in more than 5% of people in the study were decreased appetite (12%), fatigue (12%), nausea (12%), fever (9%), and asthenia (7%).

Metastatic urothelial bladder cancer is associated with a poor prognosis and limited treatment options. According to the American Cancer Society, it is estimated that more than 74,000 Americans will be diagnosed with bladder cancer in 2014, with approximately 15,000 new diagnoses made when the disease is in advanced stages.

The study results in advanced bladder cancer patients “point to a new era in cancer treatment for a disease that has not seen a major advancement since the introduction of cisplatin-based combination chemotherapy in the 1980s,” said Dr. ­Petrylak.

FDA Grants Breakthrough Therapy Designation

The U.S. Food and Drug Administration (FDA) has granted MPDL3280A Breakthrough Therapy designation to expedite the development and review of the drug and to help ensure patients have access to it through FDA approval as soon as possible. The agent is being evaluated in a broad range of tumors, noted Sandra Horning, MD, Chief Medical Officer and Head of Global Product Development for Genentech. Dr. Horning noted that MPDL3280A pivotal studies including a diagnostic test have been started in lung and bladder ­cancers. ■

Disclosure: Dr. Powles has served in a consultant or advisory role for Genentech and GlaxoSmithKline. Dr. Petrylak has received honoraria from Genentech. For disclosure information for all study authors, visit


1. Powles T, Vogelzang NJ, Fine GD, et al: Inhibition of PD-L1 by ­MPDL3280A and clinical activity in patients with metastatic urothelial bladder cancer. Abstract 5011. Presented at the 2014 ASCO Annual Meeting, May 31, 2014.