The research is featured on the Nature cover
Professor Tom Powles and his clinical colleagues in the UK, USA, Spain and France, have made a breakthrough in developing a new therapy for advanced bladder cancer, for which there have been no major treatment advances in the past 30 years.
A new strategy
Published today in Nature, the trial tests an antibody called MPDL3280A that blocks a protein thought to help cancer cells evade immune detection: PD-L1 (programmed death ligand 1) is found on the surface of some bladder cancer cells.
The drug is known as an immune checkpoint blocking antibody and can renew anti-tumour immune system activity. If we thought of PD-L1 as a kind of cancer cell camouflage paint, MPDL2380A would be the soap that washes it away, making the cancer cells visible again to patrolling immune cells.
Bladder cancer is the 7th most common cancer in the UK and around 10% of diagnoses are advanced (meaning the cancer has already spread - metastasised - to another part of the body). This makes it very difficult to treat, with chemotherapy the only option. On average patients live 12-18 months following diagnosis, with many choosing to forego chemotherapy due to its toxicity and limited survival benefit.
The study recruited 68 metastatic urothelial bladder cancer (UBC) patients who had not responded previously to available standard treatments (platinum-based chemotherapy). In this phase one, multi-centre international clinical trial, they were given MPDL3280A, an immunotherapy being developed by Roche. Patients were also tested for PD-L1 expression, using immunohistochemistry on tumour biopsies, and just under half had PD-L1 positive tumours.
High-grade papillary urothelial carcinoma
(Nephron, Wikimedia Commons, cc-by-sa 3.0)
After six weeks of treatment, 43 per cent of PD-L1-positive patients found their tumour had shrunk. This rose to 52 per cent after 12 weeks’ follow up. Two patients’ (7 per cent) radiological imaging found no evidence of the cancer at all following the treatment. Among PD-L1 negative patients, 11 percent responded positively to treatment too.
Patients with positive responses found the benefits were prolonged, and safety results were also encouraging, with fatigue and loss of appetite most commonly reported as side effects – far more tolerable than non-targeted chemotherapy, especially in the older patients who commonly present with advanced UBC.
The early results of this trial are so promising that the MPDL3280A antibody drug has been given breakthrough therapy designation status by the FDA. This priority status is only given to drugs that are intended to treat life-threatening conditions and for which we have good clinical evidence to suggest they are significantly better than what is currently available.
Prof. Powles is Lead Author and Consultant Medical Oncologist. He said:
“This study is a hugely exciting step forward in the search for alternative advanced bladder cancer treatment. For decades chemotherapy has been the only option, with a poor outcome and many patients too ill to cope with it. Not only has this investigational drug had a striking response rate, we can target this therapy for patients by screening specific protein PD-L1.
“We now need larger trials to confirm our findings, and as this drug has been given breakthrough designation status by the FDA, we hope to fast track this process so we can begin to give hope to the thousands of people affected by advanced bladder cancer each year.”
Today the journal highlights this trial in a small selection of publications of interest. Also published in the same issue are broader results of this phase one study for the antibody MPDL3280A, with data from lung, kidney, colon, and head & neck cancers, authored by Professor Roy Herbst at the Yale Cancer Centre.
Nature research highlights in the issue; the research is featured in the antitumour immunity section
In addition to these early findings being exciting for bladder cancer patients, there have also been studies suggesting the antibody could help those with non-small cell lung cancer (NSCLC) and melanoma skin cancer.
We also take this opportunity to congratulate Professor Powles on delivering his inaugural lecture successfully on November 24th.
Left to right: Prof Mike Curtis (Deputy Vice-Principal for Health), Prof Tom Powles (lead author), Prof Nick Lemoine (BCI Director, Dr Rob Bennett (QMUL Chief Operating Officer).
Inaugural lectures are an opportunity for researchers to look back and tell us how they got to where they are, what drives them, to whom they are grateful and what they look forward to in the future.
Thank you all who attended and enjoyed the celebration!
MPDL3280A (Anti-PD-L1) treatment leads to clinical activity in metastatic bladder cancer.
T Powles, JP Eder, GD Fine, FS Braitch, Y Loriot, C Cruz, J Bellmunt, HA Burris, DP Petrylak, SM Teng, X Shen, Z Boyd, PS Hegde, DS Chen, NJ Vogelzang. (2014) Nature 515; 558–562
BBC News - Bladder cancer: 'Exciting' drug breakthrough
Daily Mail - Drug hope in fight against cancer of the bladder: New treatment that helps to turn patients' immune system back on shrank tumours
Telegraph - First major treatment for bladder cancer in 30 years discovered by scientists
Mirror - Wonder drug cures two bladder cancer patients and now more will be tested
Huffington Post - Scientists Discover 'Breakthrough' Drug That Could Cure Bladder Cancer
Science Magazine - Multiple boosts for cancer immunotherapy
Tech Times - Bladder Cancer Breakthrough Treatment Developed after 30 Years