Breakthrough in the treatment of bladder cancer (and perhaps not only it)
Researchers at the Barts Institute of Oncology, part of Queen Mary University of London, in collaboration with colleagues from other institutions in the UK, as well as the USA, Spain and France, have made a breakthrough in the treatment of late-stage bladder cancer, which has hardly changed over the past 30 years.
A new approach is to use the immunotherapy drug MPDL3280A developed by Roche, the active ingredient of which is antibodies that block the PD-L1 protein (programmed cell death ligand-1) expressed on the surface of a part of bladder cancer cells. It is believed that this protein helps malignant cells to avoid recognition by the immune system.
The drug exerts its effect through the mechanism of restoring the antitumor activity of the immune system, known as "checkpoint blockade", or blockade of immune control points. If we imagine that the PD-L1 protein is a kind of camouflage paint that hides cancer cells from the immune system, then MPDL3280A antibodies act as a soap that washes off this paint and makes the cells visible to immune cells.
In the UK, bladder cancer ranks 7th in frequency of occurrence. At the same time, about 10% of cases are detected in the late stages of the disease, accompanied by metastasis of the tumor to other parts of the body. This makes treatment much more difficult, making chemotherapy the only acceptable approach. On average, patients die 12-18 months after diagnosis, while many of them refuse chemotherapy because of its high toxicity and low effectiveness.
The authors conducted an international multicenter phase I clinical trial of the new drug, which involved 68 patients with metastatic urothelial bladder cancer who did not respond to standard platinum chemotherapy. As part of the study, all participants were treated with MPDL3280A. In addition, a biopsy of tumor material was taken from each of them, which was immunohistochemically analyzed for PD-L1 protein expression. The analysis showed that almost half of the patients had PD-L1-positive tumors.
A survey conducted 6 months after the end of therapy showed that 43% of PD-L1-positive tumors decreased in size. 12 months after the therapy, this indicator increased to 52%. In two patients (7%), X-ray examination revealed no signs of a tumor at all. Also, a positive reaction to treatment was recorded in 11% of patients with PD-L1-negative tumors.
The patients who responded to therapy noted the stability and duration of positive effects. In addition, very promising safety research results have been obtained. The most common adverse events were chronic fatigue and lack of appetite, which distinguishes the new therapy from traditional chemotherapy drugs, which are much worse tolerated, especially by elderly patients who are usually diagnosed with severe forms of bladder cancer.
The early results of the clinical trial are so promising that the US Food and Drug Administration (FDA) has assigned the antibody drug MPDL3280A the status of breakthrough therapy. Such a priority status is assigned only to drugs intended for the treatment of life-threatening diseases, the higher effectiveness of which in comparison with traditional medicines has been proven by convincing clinical data.
According to the head of the study, Professor Tom Powles, at this stage it is necessary to conduct larger clinical trials. He hopes that, thanks to the status of breakthrough therapy assigned by the FDA, such studies will be launched as soon as possible.
Currently, the antibody drug MPDL3280A is also undergoing phase I clinical trials as a drug for the treatment of lung, kidney, rectal, head and neck cancers, as well as melanoma.
Article by et al. MPDL3280A (anti-PD-L1) treatment leads to clinical activity in metastatic blader cancer published in the journal Nature.
Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru based on the materials of the Barts Cancer Institute:
Nature: BCI-led trial of breakthrough therapy for advanced bladder cancer.
01.12.2014