Igor Richter, Josef Dvořák, Jiří Bartoš
Jaromír Roubec, Jaromír Richter
Vladimír Červeňák, Alena Berková, Zdeněk Chovanec, Jiří Vaníček, Tomáš Hanslík, Sabina Svobodová
Zdeněk Chovanec, Michal Reška, Alena Berková, Vladimír Červeňák, Jiří Veselý, Zdeněk Dvořák, Tomáš Hanslík, Adam Peštál, Vadym Prudius, Ivan Čapov
The systemic treatment of malignant tumors has undergone significant changes in recent years. In addition to the hormonal treatment and chemotherapy, we have new therapeutic approaches as immunotherapy or targeted treatment. Many new drugs are added in the treatment of malignant tumor every year. The treatment guidelines have been updated and changed. The aim of this review is to provide summary of new drugs in treatment of solid tumors. This article presents an overview of the two groups of agents as tyrosine kinase inhibitors and monoclonal antibodies, due to extensive issues.
Epidermal growth factor receptor – its importance, diagnosis and development of treatment in non‑small cell lung cancer
The epidermal growth factor receptor (EGFR) is a transmembrane glycoprotein with a binding site for a family of extracellular protein epidermal growth factor ligands. The epidermal growth factor receptor is a member of the ErbB (erythroblastic leukemia viral oncogene) receptor family, which consists of a total of four members of closely related receptor tyrosine kinases: EGFR (ErbBI or HER1), ErbB2/neu (HER2), ErbB3 (HER3) and ErbB4 (HER4). Epidermal growth factor and its receptor were discovered by Stanley Cohen. In 1986, Cohen shared the Nobel Prize in Medicine with Rita Levi-Montalcini for his discovery of growth factors. The signal from EGFR can be transmitted by a number of intracellular transporters RAS-RAF-MAPK (leading to cell proliferation), or the singular pathways JAK-STAT3 or PI3K-AKT (affecting cell survival) are activated. Examination of the mutational status of this receptor plays a crucial role in deciding on the treatment of non-small cell lung cancer and is the goal of so-called biological treatment.
Metastatic non-small cell lung cancer represents a disease with poor prognosis. Introducing tyrosine kinase inhibitors of specific mutations into daily practice improved the prognosis of a group of patients, however for majority of the patients before the era of immunotherapy the chemotherapy was the only option. Several molecules working as immunotherapeutic agents have proven their effectivity and safety in the first and second line of palliative treatment of the lung cancer. Recently the combination of nivolumab with ipilimumab was introduced into the clinical practice based on the CheckMate 227 and CheckMate 9LA trials. Combined immunotherapy with nivolumab and ipilimumab represents a new treatment option for patients with non-small cell lung cancer without specific mutations regardless of programmed cell death-ligand 1 (PD-L1) expression. Registration in the Czech Republic as well as health care reimbursement is unfortunately missing at this moment for this new combination.
Consolidation immunotherapy with durvalumab in the treatment of locally advanced non‑small cell lung cancer
In about a quarter of cases, non-small cell lung cancer (NSCLC) is diagnosed at the stage of locally advanced disease. The standard treatment for these patients is concomitant chemotherapy and radiotherapy. Currently, immunotherapy is an integral part of the treatment of the NSCLC treatment algorithm, especially anti-PD-1 and anti-PD-L1 check-point inhibitors. Data from the PACIFIC study demonstrated a significant benefit of consolidating immunotherapy with the anti-PD-L1 monoclonal antibody durvalumab after cessation of radiotherapy, including prolongation of overall survival. Durvalumab is currently the reference molecule in this indication. Tolerance and safety profile are favorable, early diagnosis and treatment of immune-related adverse events is necessary.
In the overview the authors discuss the actual approaches in the concomitant chemoradiotherapy based on the previous results and meta-analysis and discuss the new possibilities in the combined chemoradiotherapy and immunotherapy of the locoregional advanced non-small cell lung cancer.
Non-melanoma skin cancer represents the most frequent cancer overall. Radiotherapy and surgery are the main treatment modalities; however, the best choice depends on tumor location, patient age, comorbidities and also patienťs preference. A small portion of these patients unfortunately progress into locally advanced or metastatic form when surgery and radiotherapy are not possible. Cemiplimab represents another check-point inhibitor molecule (belongs among programmed cell death protein 1 receptor inhibitors [PD-1]) which has proven effectivity and safety in clinical trials for the treatment of locally advancedor metastatic squamous cell and basal cell carcinoma where surgery and radiotherapy are not feasible. Cemiplimab is another reasonable treatment choice for this group of patients since effectivity of conventional chemotherapy is limited.
Immunotherapy in the adjuvant treatment of malignant melanoma in patients with the highest risk of metastases
Adjuvant treatment of malignant melanoma developed significantly in recent 20 years. Twenty years ago, just interferon-based therapy was available in adjuvant treatment of malignant melanoma. Recently, due to beginning of anti-programmed death-1(anti-PD-1) therapy era is this therapy significant benefit for patient suffering malignant melanoma. In 2015 CHECKMATE 238 trial was published proving efficacy of anti-PD-1 therapy in adjuvant setting. Later, another trial - KEYNOTE 054 trial was published, confirming efficacy of pembrolizumab in adjuvant setting. Recently, we can use anti-PD-1 therapy in adjuvant treatment of malignant melanoma routinely. The most significant advantage of anti-PD-1 therapy is efficacy and safety with small rate of serious adverse effects. But we should mind, even the rate of serious adverse event is low, the risk of serious complications is still present. In this reason should be used in patients which would have benefit from this treatment.
Prostate cancer represents a most frequent tumor among men. Despite high success rate of locoregional treatment some patients will finally relapse and develop castration resistant disease even without metastases. Apalutamid represents a new treatment modality in the treatment of this stage of prostate cancer. Apalutamid has shown statistically significant prolongation of the median of the metastasis-free survival as well as time to symptomatic progression. Apalutamid represents new possibility in the treatment of castration resistant prostate cancer without distant metastases.
Metastatic breast cancer is still an uncurable disease. The prognosis of patients with HER2-positive metastatic breast cancer before the implementation of trastuzumab was poor. This targeted treatment to receptors dramatically improved the fate of patients regarding overall survival and a decrease in difficulties. A number of effective drugs has been invented since trastuzumab was implemented as the standard treatment in the last century - pertuzumab, trastuzumab emtansin (T-DM1) and lapatinib. Despite this almost all patients will suffer progression of disease and it is necessary to develop new drugs and methods. This type of cancer metastasizes to the brain very often and new drugs seem to be effective in that situation.
Diffuse large B-cell lymphoma represents heterogenous group of diseases. Standard therapy of first line is R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) leading to 60% probability of long-term remission. Approximately 40% of patients relapse or the disease is primary refractory. Prognosis of this patient is unfavourable. Standard treatment approach in younger relapsed DLBCL patients is salvage chemotherapy with autologous stem cell transplantation. Only few options are available in group of elderly patients with relapsed DLBCL, mostly combination of bendamustine and rituximab or gemcitabine-based regimens. There are several new treatment options, especially therapy with genetically modified T-lymphocytes (CAR-T), polatuzumab vedotin in combination with bendamustine and rituximab or bispecific antibodies. This targeted therapy to DLBCL subtypes will surely be a large part of how to successfully treat the relapsed DLBCL patients in future.
The advances in molecular biology of gastrointestinal stromal tumors (GIST) in recent years has allowed to distinguish various tumor subtypes that respond differently to anticancer therapy. This fact together with the development of new active drugs has led to the changes in standards of care in both adjuvant and palliative settings.
Bone metastases are the major cause of morbidity and sometime mortality of patients with malignant tumours. The cancer with metastases is an incurable disease, however bone metastases are well influenced by modern systemic treatment targeted to bone - bisphosphonates and denosumab - bone modifying agents (BMA). This treatment significantly improves the quality of life of patients with bone metastases and often prolongs their life. However, it is necessary to be able to handle these substances. It is very important to start treatment early, long-term treatment, cooperation with patient and prevention and management of side effects. Bisphosphonates and denosumab are also indicated in the treatment of osteoporosis, but at a much lower dose than in the treatment of bone metastases. BMA therapy related osteonecrosis of the jaw is very difficult to treat and often leads to interruption or termination of this therapy. It is extremely important to prevent this undesirable situation.
In the case report, we can present atypical course of primary central nervous system lymphoma (PCNSL) in the patient, who was exposed to long-term immunosuppressive therapy for idiopathic bowel disease. In the literature and in clinical practice as well, the PCNSL are thought to exclusively occur in the CNS. Our rare case brings the evidence about extracerebral systemic relapse. It is questionable, if this course is related to previous exposition to immunosuppression.
Long‑term response to sequential treatment with tyrosine kinase inhibitors in a patient with EGFR+ adenocarcinoma – case report
Lung cancer is one of the tumours with very bad prognosis. Patients with epidermal growth factor receptor (EGFR) positive lung cancer are treated with tyrosine kinase inhibitors with good treatment tolerance and statistically significant improved survival outcome. Case report presents long survival of the 78 years old patient with EGFR positive non-small cell lung cancer on targeted therapy.
Lung cancer is the third most common malignant process in both women and men. Lung adenocarcinoma with lepidic growth is a variant that is characterized by its proliferative growth along intact alveolar walls. More women and non-smokers tend to be affected. Early diagnosis reveals a tumor process in the non-invasive or mini-invasive stage, and the prognosis for five-year survival is around 100%. The imaging method of choice is computed tomography, where a typical image of carcinoma with lepidic growth is the subsolid nodule. Theoretical information concerning this unusual diagnosis is supplemented in the article by a clear case report of a female patient with colorectal cancer and a subsolid nodulus of the left upper pulmonary lobe, in which histological examination confirmed the diagnosis of lung adenocarcinoma with lepidic growth.
This case report presents the case of a 68-year-old man, who presented with slow-growing, slightly painful infiltration in the lower half of the sternum observed for two years. According to the performed computed tomography examination, a 7 * 6 * 6.5 cm infiltration of the middle part of the sternum was found. Lesion was extending 1 cm ventrally and 4 cm dorsally into the surrounding soft tissues. An open biopsy was performed with the finding of moderately differentiated (grade 2) conventional chondrosarcoma. Subsequently a multidisciplinary team composed of: the Musculoskeletal tumour committee of the Masaryk Oncology Institute in Brno, the 1st Orthopaedic Clinic of St. Anne's Faculty Hospital in Brno and the 1st Surgical Clinic of St. Anne's Faculty Hospital in Brno had referred the patient to plan and perform the surgical resection of the tumours lesion. A partial resection of the sternum with the tumor was performed, followed by reconstruction of the defect with two condensed polytetrafluoroethylene meshes using the so called „sandwich technique". Then the defect was strengthened using titanium splints and subsequently reconstructed by pectoralis major muscle flap. Definitive histology confirmed the finding of grade 2 conventional sternal chondrosarcoma.