Selected articles

Articles for label Poprach Alexandr are displayed.. Show all articles

Combination immunotherapy and tyrosine kinase inhibitors with immunotherapy in patients with metastatic renal cell carcinoma

04/2020 MUDr. Alexandr Poprach, Ph.D.; MUDr. Radek Lakomý, Ph.D.
The treatment of patients with mRCC is still palliative, but recently we have the results of several studies combining modern therapy, where we have seen a significant increase in time to disease progression and overall survival compared to tyrosine kinase inhibitors (TKI), as well as the numbers of overall treatment responses. We must not forget that if there is a therapeutic response to immunotherapy, it is often long-term again compared to TKI, which is particularly underlined for complete remissions. In this review below we will present the current results of three studies combining advanced immunotherapy with TKI or a combination of anti-programmed cell death protein 1 (anti-PD-1) antibody with anti-cytotoxic T-lymphocyte associated antigen 4 (anti-CTLA-4) antibody.
ENTIRE ARTICLE

Advances in adjuvant treatment for high‑risk BRAF mutated malignant melanoma

05/2019 MUDr. Radek Lakomý, Ph.D., MUDr. Alexandr Poprach, Ph.D.
Surgical excision is the curative treatment in most cases of early cutaneous melanoma. Prognosis of patients with high-risk primary melanoma or with nodal involvement remains poor. Impact of adjuvant interferon alfa on overall survival is limited. The recently published results from the randomized phase III trials with immunotherapy - anti-PD-1 antibodies (nivolumab, pembrolizumab) and with targeted therapy (dabrafenib + trametinib) are very promising. These new adjuvant treatment modalities are able significantly reduce the rate of disease recurrence. However, there are many unresolved questions. Especially, we do not know what is better in BRAF mutant melanoma, if targeted therapy or modern immunotherapy? We need reliable biomarkers of tumor progression and prognosis for better selection really high-risk patients and the optimal type of adjuvant treatment. The side effect profile of treatment and patient preference will play an important role in decision-making process.
ENTIRE ARTICLE

The fatal side‑effect after the first dose of nivolumab – case report

03/2019 Doc. MUDr. Alexandr Poprach, Ph.D.; MUDr. Radek Lakomý, Ph.D.
The patients with metastatic malignant melanoma had a very poor prognosis in the past, chemotherapy was highly palliative and not so efficient. The use of checkpoint inhibitors (such as the anti-PD-1 antibody nivolumab) changed the prognosis and treatment results. The probability of 5-years overall survival is approximately 50 % by using the combination of anti-CTLA-4 and anti-PD-1 antibodies. However, the use of checkpoint inhibitors could cause the immune-related side effects that may be fatal. Herein we introduce a story of our patient with metastatic renal cell carcinoma with Guillain-Barré syndrome after the first dose of nivolumab. We had treated him with combined immunosuppressive therapy, plasmapheresis and intensive supportive care but he died of this complication in the end. The onset of first signs of this side effect was 5 days after the first dose of nivolumab which is remarkable.
ENTIRE ARTICLE

The indication of immunotherapy in renal cell carcinoma and other urological tumours

Supplementum 01/2019 Imunoterapie
MUDr. Alexandr Poprach, Ph.D.; MUDr. Radek Lakomý, Ph.D.
The checkpoint inhibitors now belong to standard treatment options with metastatic renal cell carcinoma patients and significantly prolong overall survival of these patients. The results of the study phase I with combinations of targeted therapy and immunotherapy are also very promising, high response rates and prolonging of progression-free survivals/overall survivals were reached. But we have to wait for studies phase III results. Immunotherapy is also successful with urothelial cancers patients, especially with responders to this treatment. There is a high need to unify various methods of assessments PD-L1 expression which has both predictive and prognostic value. It was proven that combination of PD-L1 expressions and mutations loads of urothelial tumors improve estimation of response rate to the immunotherapy. The immunotherapy is very expensive, so it is important to have valid and reliable predictive factors. In this review, we summarize the up-to-date results of studies with immunotherapy, with renal cell carcinoma patients and urothelial cancers patients.
ENTIRE ARTICLE

The development of checkpoint inhibitors and their clinical use

Supplementum 01/2019 Imunoterapie
MUDr. Radek Lakomý, Ph.D.; MUDr. Alexandr Poprach, Ph.D.
The progress in anticancer immunotherapy has been remarkable in the last decade. The concept of immune checkpoint blocade with monoclonal antibodies (checkpoint inhibitors) has opened a new way in the treatment of cancers. Immune checkpoint inhibitors restore and augment antitumor functions of cytotoxic T cells. Efficacy and acceptable safety of immune checkpoint inhibitors have been demonstrated in many clinical trials. Checkpoint inhibitors are now approved for treatment of variety cancers and intensive research on others is under way. There are still many challenges. More than anything else we urgently need reliable biomarkers of efficacy and toxicity. Then we will be able to better select suitable patients for treatment. Immunotherapy is rightly considered to be the fifth pillar of anticancer treatment, next to surgery, radiotherapy, chemotherapy and targeted therapy.
ENTIRE ARTICLE

Cabozantinib in the treatment of renal cell carcinoma

05/2017 MUDr. Alexandr Poprach, Ph.D., MUDr. Radek Lakomý, Ph.D.
Disseminated renal cell carcinoma is incurable. In the second line of palliative treatment, we can now usually use everolimus or axitinib. The breakthrough in treatment in the second line is the results of Phase 3 studies (METEOR - Cabozantinib study and CHECKMATE 025 - Nivolumab study). Nivolumab prolonged overall survival when compared to everolimus, the time to progression was the same, but cabozantinib prolonged both progression and overall survival when compared to everolimus. Cabozantinib is an oral inhibitor of many receptor tyrosine kinases. Unlike other commonly used multi-enzyme inhibitors that are used in renal cell carcinoma, it also inhibits MET and AXL protein kinases. These are more pronounced in patients after sunitinib treatment and also in patients in a poor prognostic group. In this review we will look at cabozantinib - the mechanism of its effect, the characteristics of the drug and the recent results of the studies.
ENTIRE ARTICLE

Immunotherapy of malignant melanoma

02/2017 MUDr. Alexandr Poprach, Ph.D., MUDr. Radek Lakomý, Ph.D.
Metastatic and/or locally advanced inoperable melanoma is still an incurable disease. On the other hand the progress in the new treatment's options causes significant prolongation of time to progression and overall survival. Treatment of metastatic melanoma could be divided into three goups. Checkpoint inhibitors - anti-CTLA-4 (cytotoxic T-lymphocyte-associated protein 4) and anti-PD-1 (programmed death 1) or PD-L1 inhibitors - are in the first group, BRAF and MEK inhibitors belong to the second group. Cytostatics are in the last group. We will point out drugs from the first group in this review and the results of the actual studies will be mentioned.
ENTIRE ARTICLE