Klaudia Regináčová, Martina Kubecová
Helena Čoupková, Renata Chloupková, Marek Konečný, Magda Bařinová, Jana Skřičková, Miloš Pešek, Vítězslav Kolek, František Salajka, Milada Zemanová, Leona Koubková, Libor Havel, Kateřina Košatová
Štěpán Rusín, Petr Jelínek
Jan Prokš, Josef Dvořák
Neoadjuvant chemotherapy is able to convert unresectable breast tumors to resectable tumors and to provide more conservative surgery in some mastectomy candidates. Chemotherapy agents, including taxanes, which are recommended in the adjuvant setting, are also considered in the neoadjuvant setting. A number of clinical studies with nab paclitaxel have also been performed in the neoadjuvant setting. Nab-paclitaxel demonstrated antitumor activity and an acceptable safety profile in the neoadjuvant treatment of breast cancer. In some clinical trials, nab-paclitaxel was more effective than paclitaxel. Ongoing and future trials will further evaluate preoperative nab-paclitaxel in breast cancer, including in combination with many novel immunological targeted therapies.
Neoadjuvant chemotherapy is a systemic treatment, which is given before a local procedure that leads to the removal of the tumor. In the treatment of breast cancer, it is intended especially for the patients in whom we want to achieve the downstaging of the tumor in order to improve its operability and to achieve breast conserving surgery. Although there is currently no longer long-term survival in patients who undergo neoadjuvant chemotherapy, patients who achieve complete pathological remission (pCR) have a better long-term prognosis. In patients with HER2 positive tumors, a significantly higher number of pCR is achieved if trastuzumab is added to neoadjuvant treatment, when dual blockade is added to the combination via simultaneous administration of trastuzumab and pertuzumab with chemotherapy, the pCR almost doubles. For this reason, pertuzumab should be used as a essential component of neoadjuvant chemotherapy in patients with high-risk HER2-positive breast cancer in combination with trastuzumab.
Trastuzumab represents one of the fundamental targeted molecule in oncological practice. Due to the high breast cancer incidence, constantly increasing patient survival with HER2 positive breast cancer the overall treatment cost is increasing rapidly. Since the patent of Herceptin has expired there is an intense effort to replace the Herceptin with cheaper equivalents. Biosimilars represents one of the possible option. Recently there are several trastuzumab biosimilars registered by EMA (Ontruzant, Kanjinti, Herzuma) and further molecules are in the approval process. The usage of the biosimilars may represent the saving about 20-30% of the original price and this could possible extend the insurance reimbursement to further indications. Biosimilars are used in Czech Republic for many years with generally good experience however due to the different approval proces of the biosimilars compared with original drugs there has to be a caution about possible side effects which may not manifest during the testing on relatively small group of patients.
Hormonal therapy allows patients with metastatic hormone-positive tumours to control disease while maintaining the best quality of life. The problem of its long-term administration is the emergence of resistance. CDK4/6 inhibitors represent a new therapeutic group of drugs when combined with hormonal agents provide significant benefit in delaying resistance and prolonging progression free survival with a favourable safety profile. The greatest benefit is apparently achieved with the use of CDK4/6 inhibitors already in the first line, but even in the 2nd line, therapy is very beneficial. Common inclusion of CDK4/6 inhibitors in therapeutic practice is expected soon, but we have to wait for results of clinical trials for the optimal therapeutic sequence.
Discrepancies between the histological findings of biopsy and the surgical specimen of breast cancer
The introduction of a thick needle core cut biopsy in the diagnosis of non-palpable and palpable breast lesions at the beginning of the 1990s gradually replaced surgical diagnostic excision. A minimally invasive method which, under a stereotactic, ultrasound or magnetic resonance guidance, allows to obtain pieces of tissue that in contrast to a fine needle biopsy can be processed by a standard histological procedure, brought the acceleration of diagnostics of malignant tumors, saved patients with benign lesions from unnecessary surgery and, last but not least, reduced costs. On the other hand, it opens the question of reliability of diagnostics, based on the minimum tissue sample, i.e. the representativeness of this sample from the viewpoint of both the basic typing of the tumor and the determination of the prognostic and predictive parameters that are the basis for subsequent treatment. The histological result of core cut biopsy is the essential source of tumor information for the indication of neoadjuvant therapy, and often the only available tumor tissue in case of complete pathological response. These facts underline the importance of the accuracy of the core biopsy diagnosis and the need for awareness of the possible discrepancies between the histological findings of biopsy and the surgical specimen, and their causes. However, they also raise pressure on introducing of measures or new methods, in an effort to eliminate these discrepancies.
Breast cancer metastases to ovaries occur either in advanced, metastatic disease. In daily practice distinguish between primary and secondary ovarian tumours is often difficult. Ultrasound is irreplaceable in diagnosis. Definitive answer often gives surgery and histological findings.
Take home message of this article is, besides technical aspects of breast surgery view by general surgeon and plastic surgeon, opening eyes to surgeons, plastic surgeons, oncologists and at least management of Czech health system. That in other countries, even in Romania, or Hungary, treatment of breast cancer is on a higher level than in our country, at least surgical and oncoplastic part of complex breast cancer therapy. Even the numbers of breast cancer are increasing. Immediate breast reconstruction should be available for every woman patient with breast carcinoma and of course the right indication.
Adjuvant radiotherapy in breast cancer using proton bundles is not yet part of any recommendations despite undisputable dosimetric benefits, including mainly lower doses for the heart, the lungs and the second-sided breast. The reason is the lack of clinical data on proton radiotherapy in breast cancer, which would confirm its theoretical advantage in practice. The results of studies evaluating cardiovascular morbidity after irradiation of the left side of the chest are not unambiguous; however, cardiac doses should be monitored and reduced even when performing photon radiotherapy. Modern techniques that allow this to happen include the technique of breath holding or irradiating only tumor beds in a certain group of patients, or by placing a patient on the abdomen using a so-called breast board. Questions about the clinical benefit of proton RT in breast cancer should be answered by ongoing clinical trials.
Precision oncology implies customizing treatment for each individual and cancer based on unique molecular and biologic characteristics. In the pregenomic era cancers are classified based on tumor site and histology. In the upcoming genomic era malignant diseases are reclassified based on molecular and biologic characteristics which results in increased number of cancer types. In the future, more and more identifiers of tumor diversity will be defined and the end of the pregenomic era of rare tumors can be expected.
The possibilities of non-small-cell lung cancer treatment are expanding on the basis of a better understanding of the molecular biology of the tumors. Identification of genetic changes has led to the development of a number of small molecule tyrosine kinase inhibitors, designed to disrupt altered signaling pathways in tumors with these genetic changes. One of these genetic changes is the anaplastic lymphoma kinase (ALK) gene transformation, in which ALK inhibitors are indicated. ALK inhibitor of the 2nd generation alectinib has proven its efficacy not only in the first-generation treatment ALK failure, but also in the first line of treatment, also thanks to its effectiveness in the CNS.
Erlotinib in the treatment of advanced non‑small cell lung cancer – present experience and results in the Czech Republic
Erlotinib is an inhibitor of epidermal growth factor receptor (EGFR) tyrosine-kinase activity, a potent drug in non-small-cell lung cancer (NSCLC) treatment. In this paper, we report a population of patients suffering from advanced NSCLC who are being treated with erlotinib in the Czech Republic under the terms of the TULUNG drug registry (excluding the patients from the University Hospital of Ostrava). By October 2nd 2017, 3763 patients were treated with erlotinib in this cohort. The overall response rate (ORR) in the entire group was 8,7 %, the disease control rate was 58,5 %. Survival data were updated on May 21st 2018. Progression-free survival and overall survival were 3,1 months and 7,7 months, respectively. In our evaluation, we noticed a statistically significant difference both in overall survival (OS) and progression free survival (PFS) in patients grouped according to status of EGFR mutation, performance status, gender and smoking habits. Moreover, there was a statistically significant difference in PFS among patients grouped according to treatment line. Based on our results, skin toxicity appears to be a prognostic factor. The efficacy difference in squamous and non-squamous carcinomas was not statistically significant. From the 3763 patients included in the safety analysis, 1592 (42,3 %) experienced therapy-related adverse events, the most common was rash (35,3 %) and diarrhea (16,3 %). Serious adverse events (G3/4) were reported in 13,6 % patients, the most common was rash (9 %) and diarrhea (3 %). Our results confirm the efficacy and safety of the erlotinib therapy in the first and in the following lines of advanced NSCLC.
Merkel cell carcinoma (MCC) is a rare neuroendocrine tumor of the skin. Approximately 80% of tumors are Merkel cell polyomavirus (MCPyV) positive and in the rest 20% high rates of UV induced mutations is proven. MCC is very aggressive malignancy with tendency to metastasize into skin, lymph nodes and distant organs. Recently used chemotherapy had quite high response rate, achieved in some cases almost 60%, but the responses were short term and they did not project into prolongation of overall survival. Implementation of immunotherapy with inhibitory monoclonal antibodies against PD-1 and PD-L1 receptors led to significant prolongation of progression free survival and overall survival in patients with metastatic MCC (mMCC). The only checkpoint inhibitor, which is currently approved by FDA (Food and Drug Administration) and EMA (European Medicines Agency) for the treatment of mMCC is avelumab. It is IgG1 monoclonal antibody against PD-L1, highly efficient in the first and further lines of treatment.
Author in this article describes crucial periods and changes in the attitude to the therapy of the local progressive and metastatic bronchogenic carcinoma during the last three decades with the accent on the rapid progress in the personalized target therapy and immunotherapy of this disease together with next perspectives in the research and clinical practice.
Bone tumors and bone metastases are one of the main sources of pain at patients with advanced oncological diseases and thus one of the main causes of lowering with quality of the in lives. They represent the loss of functional independence of a patient, limit the ability to participate in common daily activities, are often associated with the terminal oncological illness and lead to far, anxiety and depression. Prevalence of pain in bone tumors is 85-100 %.
Patient with metastatic colorectal cancer treated in the third line of therapy with trifluridin/tipiracil
2015 was approved, after the placebo controled phase III trial RECOURSE, trifluridin/tipiracil (Lonsurf®, formerly TAS 102) for the treatment of patients with metastatic colorectal cancer who have been treated with fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy, an anti-VEGF biological therapy, and if RAS wild-type, an anti-EGFR therapy. Trifluridin/tipiracil is an oral analog of fluoropyrimidin in combination with thymidinfosforylase inhibitor. Following case report demonstrates efficiency and good tolerance in the third line of therapy of the patient with metastatic colorectal cancer.
The review explains historical development of pricing and reimbursement regulation of pharmaceuticals in the Czech Republic. It mentions time milestones with references to the key parts of the legislation related to the process of appraisal and assessment in pricing and reimbursement of therapies. In the CR, the determined reimbursement prices and conditions are a result of a complex evaluation of the added value represented by the assessed pharmaceutical, which reflects its level of comparative efficacy, safety, and quality-of-life benefits, compared to the other medicinal approaches and technologies reimbursed from the public health insurance resources in the relevant indication.