State of effects: a database of dangerous side effects of advanced cancer drugs has been created in the Russian Federation

A database has been created in Russia that contains information about the serious adverse effects of immuno-oncological drugs. This is an advanced class of drugs, for the development of which the Nobel Prize was awarded in 2018. However, during treatment, patients often experience immune reactions, endocrine disorders, disorders of the gastrointestinal tract and other dangerous phenomena. Developers of new drugs will use the created tool when planning clinical trials to select the optimal dosage of the drug without losing its effectiveness. Read more about the innovation in the Izvestia article.

Immuno-oncological drugs in the Russian Federation

Scientists at the Center for Mathematical Modeling in Drug Development at Sechenov University have created and registered the first database that contains information about the side effects of checkpoint inhibitors and their combinations in immuno-oncological drugs. These drugs have changed the approach to cancer treatment and opened a new era in cancer therapy, the developers said.

However, despite the significant advances in the treatment of the disease achieved with their help, they also have undesirable effects that need to be taken into account. The database will be used by developers of new drugs to select the optimal dosage of the drug when planning clinical trials.

Photo: IZVESTIA/Eduard Kornienko

"We started collecting the database back in 2018, the year we received the Nobel Prize," Kirill Peskov, head of the Center for Mathematical Modeling in Drug Development at Sechenov University, told Izvestia. — At that time, all major checkpoint inhibitors were already available on the market and a pool of clinical data on the safety of various types of therapies had accumulated.

Photo: IZVESTIA/Eduard Kornienko

Currently, several key checkpoint inhibitors are available on the Russian and foreign markets — PD-1 molecule inhibitors (drugs Pembrolizumab, Nivolumab); PD-L1 inhibitors (Durvalumab, Atezolizumab) and CTLA-4 inhibitors (Ipilimumab, Tremelimumab). These drugs are used to treat melanoma, various types of lung cancer, kidney cancer, bladder cancer and other cancers, both as monotherapy and in combination with several drugs or in combination with chemotherapy. Side effects that may occur when using immuno—oncological drugs include immune reactions, endocrine disorders, disorders of the gastrointestinal tract, and others. Their monitoring is important not only for monitoring the patient's condition during treatment, but also for selecting the optimal dosage regimen for new drugs under development.

Database of undesirable effects of cancer drugs

The developed database contains information on serious adverse events of immuno-oncological drugs registered during clinical trials. It included information on the frequency of such side effects, the specifics of taking medications (dosage and frequency of administration, dosage regimen, use in combination with other drugs, line of therapy), as well as data on the features of the study design — the type of cancer, age and gender of patients.

The database is constantly updated. The developers include information on the results of clinical trials of innovative checkpoint inhibitors and biosimilars that are appearing in Russia and around the world. The technology will become part of a digital platform for mathematical modeling of oncological diseases for the development of new drugs being created at Sechenov University.

Photo: IZVESTIA/Sergey Lantyukhov

— Having evaluated different safety profiles of drugs related to their dose and concentration in the body, we set ourselves the task of creating a new tool for predicting the safety of immuno-oncological therapies as part of a digital platform. It will allow drug developers to find optimal solutions for the combination of drugs, dose, and dosage regimen of each component. We also plan to include data on the effectiveness of such drugs in the model. This will significantly expand the application value of our digital platform," Kirill Peskov added.

This database is very important for predicting adverse events against the background of drug treatment of cancer patients, said Oleg Kaganov, an expert at the NTI Bionic Engineering in Medicine Competence Center at SamSMU.

"Based on it, we can accurately assess the risk of complications and adjust therapy," he said.

This is an important tool for the development of personalized therapy in oncology, said Andrey Lomonosov, Deputy head of the NTI HealthNet Biomedicine working group, Scientific Consultant at R-Pharm JSC.

Photo: IZVESTIA/Eduard Kornienko

— I must say that the main breakthrough of the last decades in the treatment of cancer has become immuno-oncological drugs. Now these drugs are already part of the treatment of the most severe forms of cancer. And one of the significant factors for the successful use of such drugs is the ability to minimize undesirable side effects from them. There are situations when therapy needs to be discontinued due to side effects, which, of course, adversely affects the results of treatment. The use of personalized dosing and prescribing of such drugs, based on a large amount of evidence, will hopefully improve the effectiveness of treatment," the specialist told Izvestia.

This is important right now, when the use of immuno-oncological drugs in a convenient injectable form, in the form of automatic injectors, begins to enter clinical practice, which will simplify their use outside the hospital, emphasized Andrey Lomonosov. In outpatient settings, when constant medical supervision is not available, the risks of severe side effects may be higher.