ESMO 2014 Press Commentary: Anti-PD-L1 Antibody Shows Promising Activity in Advanced Bladder Cancer after Decades of Silence

Corrigendum:

Please note the updated data for the response rate is 52% instead of 43%

Lugano/Madrid, 29 September - Promising activity in advanced bladder cancer after decades of silence, according to Dr Maria De Santis, medical oncologist at the Centre for Oncology and Hematology and Kaiser Franz Josef Hospital, Vienna, Austria. De Santis said that emerging data on the antibody “give hope for a new and effective treatment strategy for advanced bladder cancer” as the latest research in the field was presented at the ESMO 2014 Congress in Madrid, Spain.

De Santis said: “Bladder cancer is the ninth most commonly diagnosed cancer worldwide, with more than 380,000 new cases each year and more than 150,000 deaths per year. It is a highly aggressive and deadly disease and no major progress has been made for more than a decade.”

She continued: “Cisplatin based combination chemotherapy is still the standard of care in advanced or metastatic bladder cancer. However, about 50% of patients are not eligible for standard cisplatin based chemotherapy because of a variety of reasons including poor performance status, impaired renal function and comorbidities.”

“Given the modest response durations with traditional cytotoxic chemotherapy, in particular in cisplatin-ineligible patients and those relapsing or progressing after platinum based combination chemotherapy, there has been an interest in exploring novel treatment strategies in this patient population,” added De Santis.

Commenting on the difficulty of treating urothelial bladder cancer, which is the most common type of bladder cancer, De Santis said: “Looking at the tumour itself, urothelial bladder cancer has a high mutational complexity. This fact makes it more difficult to treat with conventional chemotherapy and specific targeted therapies. This same fact offers the potential for many neo-antigens to be seen as foreign by the host immune system and might be an advantage for immunotherapy to work in bladder cancer.”

It has been known for many years that urothelial bladder cancer is an immune-responsive disease, said De Santis. “This goes back to the treatment of non-muscle invasive bladder cancer with instillation of bacillus Calmette-Guérin (BCG) into the bladder. BCG proved to be able to significantly reduce the progression to muscle invasive bladder cancer or to metastases and treatment with BCG resulted in superior 10 year disease specific survival.”

“The immune system is also active in muscle invasive urothelial bladder cancer,” continued De Santis. “CD8 tumour-infiltrating lymphocytes in the primary tumour have been shown to be predictive of survival.2 In addition the presence of some immune co-regulatory proteins (including PD-1) in advanced or metastatic urothelial cancer is frequent, and some of them correlated with survival.

Inhibition of PD-L1 interactions can restore antitumour T-cell activity and enhance the cellular immune attack on antigens. The anti-PD-L1 antibody MPDL3280A is a novel immunotherapeutic approach that has proven noteworthy activity in heavily pre-treated patients with metastatic urothelial bladder cancer in early phase trials. A promising 52% response rate ^corrigendum in a subset of patients was recently reported, including some complete responses and a considerable number of durable responses. “Such results have been lacking with conventional chemotherapy,” said De Santis.

PD-L1 inhibition is also being explored further as first-line treatment in cisplatin-ineligible patients. De Santis said: “Higher grade toxicities with MPDL3280A were very rare and there has been no evidence of renal toxicity so far. This fact is of major importance because many bladder cancer patients are elderly, have a decreased performance status and suffer from renal function impairment and other comorbidities.”

She concluded: “For the first time in many years exciting news has emerged for patients with bladder cancer. Immunotherapy and, more specifically, treatment with the engineered anti-PD-L1 antibody MPDL3280A may offer a new, effective, safe and well tolerated treatment option for advanced and metastatic bladder cancer patients while preserving quality of life. Further studies are needed to confirm the preliminary data. Most importantly, these early data are important enough for a breakthrough therapy designation that has been granted by the FDA.”

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Notes to Editors

808O: Inhibition of PD-L1 by MPDL3280A leads to clinical activity in pts with metastatic urothelial bladder cancer (UBC)

Corrigendum:

The updated data for the response rate is 52% instead of 43%

Session info

808O: Monday, September 29, 2014 – 11:00 AM – 12:30 PM - Hall Sevilla