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Investigational immunotherapy MPDL3280A (anti-PDL1) shrinks tumours in 43% of people with advanced bladder cancer

A new investigational immunotherapy MPDL3280A has been shown to shrink tumours in 43% of people (13/30) who had previously been treated for advanced urothelial (UBC) with a specific type of tumour (PD-L1 positive).1 It is thought that PD-L1 plays a part in supressing the immune system in patients and MPDL3280A is designed to make cancer cells more vulnerable to the body’s immune system. The results of this Phase I trial are particularly important as metastatic bladder cancer – dubbed the ‘forgotten killer’2- is an area of high unmet need for which there have been no new advances in treatment methods for nearly 30 years.3 In 2011, there were 5,081 deaths from bladder cancer in the UK.4

Complete response (disappearance of visible tumours on scans) was demonstrated in 7% of patients (2/30).1 The results show that treatment-related Grade 3 (severe) adverse events (AEs) occurred in 4% (3/68) of people in the study and there were no life-threatening or fatal (grade 4-5) treatment related AEs.1 Roche is developing a companion immunohistochemistry (IHC) test to help identify people who are most likely to respond to MPDL3280A, which will be validated in pivotal trials. The results of the study are being presented as a late-breaking abstract by the lead investigator, Professor Thomas Powles, Barts Cancer Institute at the Queen Mary University of London at the American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago.

“We are excited by these early stage results which show promising outcomes for patients with advanced urothelial bladder cancer” said Professor Thomas Powles at Barts Cancer Institute’s Cancer Research UK Experimental Cancer Medicine Centre and Barts Health NHS Trust, “Bladder cancer is the seventh most common form of cancer in the UK and there have been no new treatment options for over 30 years. It is therefore imperative that we continue to investigate emerging therapeutic options, particularly in advanced forms of the disease where the outlook for patients is particularly poor.”

Approximately 10,400 people are diagnosed with bladder cancer each year in the UK, making it the seventh most common cancer overall and the fourth most common cancer among men.5 Advanced bladder cancer can be particularly difficult to treat and the outlook is poor for patients compared to those who have been diagnosed early.6 Research published recently in the Journal of Clinical Urology found that survival from bladder cancer is worsening in England.7 Despite the number of new cases in bladder cancer falling, the number of deaths has not reduced by a similar proportion and is currently higher than other countries in Europe with similar incidence rates.7

About 90% of bladder cancers in the UK are urothelial which means they have developed in the cells of the bladder lining (urothelium). Because they line the bladder, these cells come into contact with waste products in the urine that may cause cancer.8

Source

1 Powles T, et al. Inhibition of PD-L1 by MPDL3280A leads to clinical activity in pts with metastatic urothelial bladder cancer (UBC). Abstract number: #5011.

2 PR Newswire. Bladder Cancer: The Forgotten Killer. Available at: http://www.prnewswire.co.uk/news-releases/bladder-cancer-the-forgotten-killer-247013811.htmlLast accessed May 2014

3 The Cancer Genome Atlas Research Network. Comprehensive molecular characterization of urothelial bladder carcinoma. Nature. 2014; 507, 315-322

4 Cancer Research UK. Bladder cancer mortality statistics. Available at: http://www.cancerresearchuk.org/cancer-info/cancerstats/types/bladder/mortality/ Last accessed May 2014

5 Cancer Research UK. Bladder cancer incidence statistics. Available at: http://www.cancerresearchuk.org/cancer-info/cancerstats/types/bladder/incidence/ Last accessed May 2014

6 Cancer Research UK. Bladder Cancer Stats and Outlook. Available at: http://www.cancerresearchuk.org/cancer-help/type/bladder-cancer/treatment/bladder-cancer-statistics-and-outlook. Last accessed May 2014

7 Eylert MF, et al. Falling bladder cancer incidence from 1990 to 2009 is not producing universal mortality improvements. Journal of Clinical Urology. 2013; 0(0) 1-9

8 Cancer Research UK. Types of Bladder Cancer. Available at: http://www.cancerresearchuk.org/cancer-help/type/bladder-cancer/about/types-of-bladder-cancer. Last accessed May 2014

9 Chen DS, et al. Molecular pathways: next-generation immunotherapy – inhibiting programmed death-ligand 1 and programmed death-1. Clinical Cancer Research. 2012;18:6580-7

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