Ročně v České republice diagnostikujeme kolem 6 000 nových případů karcinomu plic. Mutace receptoru 2 pro lidský epidermální růstový faktor (human epidermal growth factor receptor 2, HER2) patří mezi vzácné mutace, které se vyskytují cca u 1-4 % nemocných s NSCLC. V případě prokázané mutace HER2 je možné používat léčebně přípravek trastuzumab deruxtekan. Trastuzumab deruxtekan je konjugát protilátky a léku, který kombinuje humanizovanou monoklonální protilátku trastuzumab s inhibitorem topoizomerázy I deruxtekanem. Tento lék se váže na HER2 na nádorových buňkách. Cytostatikum deruxtekan je společně s HER2 internalizován do nádorové buňky, kde způsobí její destrukci. Kazuistika pacientky léčené trastuzumab deruxtekanem dokládá význam plošného použití sekvenování příští generace v indikovaných případech, zejména u nekuřáků s neskvamózní histologií. Dále ukazuje na nutnost správného čtení výsledků genetického testování a zaznamenávaní výsledků do dokumentace nemocného, aby se informace o přítomné řídicí mutaci v průběhu léčby neztratila.
Around 6,000 new cases of lung cancer are diagnosed annually in the Czech Republic. Human epidermal growth factor receptor 2 (HER2) mutations are rare mutations that occur in approximately 1-4% of patients with NSCLC. In the case of a proven HER2 mutation, it is possible to use the drug trastuzumab deruxtecan in the treatment. Trastuzumab deruxtecan is an antibody-drug conjugate that combines the humanized monoclonal antibody trastuzumab with the topoisomerase I inhibitor deruxtecan. This drug binds to HER2 receptors on tumor cells. The cytostatic drug deruxtecan, together with the HER2 receptor, is internalized into the tumor cell, where it causes its destruction. The case report of a patient treated with trastuzumab deruxtecan demonstrates the importance of widespread use of next generation sequencing in indicated cases, especially in non-smokers with non-squamous histology. It also points to the necessity of correct reading of the genetic testing results and recording the results in the patient's documentation so that information about the present control mutation is not lost during the treatment.
BACKGROUND/AIM: Cemiplimab in patients with non-small cell lung cancer (NSCLC) with PD-L1 (programmed death ligand type 1) expression ≥50% showed a significant improved overall survival (OS) with increasing expression of PD-L1. To our knowledge there exist no similar data published for pembrolizumab regarding the increased OS in relation to the PD-L1 expression. Therefore, the objective of our study was to determine whether improvement in OS reflects increased expression levels of PD-L1 (≥50%) in patients with NSCLC. PATIENTS AND METHODS: Retrospective data from 9 Czech and 1 Polish comprehensive oncology Centers were used. All patients with stage IV NSCLC and PD-L1 expression ≥50% treated with pembrolizumab in daily practice were included. The groups of patients according to the expression of PD-L1 were determined as follows: PD-L1 50-59%, 60-69%, 70-79%, 80-89% and 90-100%. The log-rank test and the Cox regression model were used to compare survival between study groups. RESULTS: A total of 617 patients were included in the study. We did not observe a statistically significant difference in OS between groups of patients with different levels of PD-L1 expression in the pooled comparison (p=0.445). Furthermore, we did not observe a statistically significant difference even when comparing OS in patients with PD-L1expression of 50-59% (reference) with the group of other patients according to the level of expression of PD-L1 in the Cox regression model including the effect covariates. CONCLUSION: PD-L1 expression showed no significant effect on OS in patients with NSCLC with PD-L1≥50% treated with pembrolizumab.
- MeSH
- antigeny CD274 * metabolismus genetika MeSH
- dospělí MeSH
- humanizované monoklonální protilátky * terapeutické užití MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádorové biomarkery metabolismus MeSH
- nádory plic * farmakoterapie mortalita metabolismus patologie genetika MeSH
- nemalobuněčný karcinom plic * farmakoterapie mortalita metabolismus patologie genetika MeSH
- prognóza MeSH
- protinádorové látky imunologicky aktivní terapeutické užití MeSH
- retrospektivní studie MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- staging nádorů MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Stage III non-small cell lung cancer (NSCLC) is a highly heterogeneous stage due to its subgroups (IIIA-IIIC) comprising both resectable and unresectable tumors. Accurate determination of the extent of the disease is essential for excluding stage IV and choosing the optimal treatment regimen. Whole body positron emission tomography and computed tomography scan (PET/CT) is recommended as an initial staging imaging in locally advanced NSCLC. Despite international guidelines for NSCLC diagnosis and treatment, they are not always adhered to due to various reasons. Even in such a groundbreaking study, the phase 3 trial PACIFIC investigating the efficacy of durvalumab as consolidation therapy in patients with stage III NSCLC PET/CT was not mandatory. With the premise that whole body PET/CT of the trunk is essential for diagnosing stage III NSCLC, we performed a retrospective study evaluating the relationship of the use of PET/CT versus conventional staging with CT of the chest and abdomen, in terms of survival. METHODS: This retrospective study of stage III NSCLC patients used the Czech lung cancer registry LUCAS, which was established in June 2018. As of the data export (up to February 9, 2022), a total of 703 patients were eligible for the analysis. Overall survival (OS) was compared using Kaplan-Meier analysis and a Cox regression model. Continuous variables were tested using the Mann-Whitney test, and categorical variables using the Pearson's Chi-square or Fisher's exact test. RESULTS: A total of 703 patients were included in the cohort with an average age of 69 years. PET/CT was performed on 354 patients, and conventional staging using chest and abdominal CT on 349 patients. The median OS among patients with PET/CT was 20.9 months [95% confidence interval (CI): 18.1-23.7], and it was statistically significantly higher (P<0.001) than among patients without PET/CT, where the median OS was 9.0 months (95% CI: 7.3-10.6). The observed effect of PET/CT was also statistically significant when comparing individual stages (IIIA, IIIB, IIIC). The multivariate Cox model confirmed the use of PET/CT as an independent prognostic factor. The most common reason for omission of PET/CT was the local or time unavailability of the examination. CONCLUSIONS: Omission of PET/CT can mean a significant decrement in survival for the patients in stage III NSCLC, likely due to poor staging and suboptimal treatment. Routine use of PET/CT is strictly recommended for the optimal management of stage III NSCLC patients even outside the high-income countries.
- Publikační typ
- časopisecké články MeSH
Resekce pokročilejších nemalobuněčných plicních karcinomů stadií II a III bez zajištění další léčbou vede k vysokému procentu recidiv. Samotná neo-/adjuvantní chemoterapie vede pouze k mírnému zlepšení přežití pacientů. Významný pokrok ve snížení šance na recidivu onemocnění přinesla až neoadjuvantní chemoimunoterapie (přičemž některé režimy pokračují i v adjuvantním podávání imunoterapie). Ačkoliv máme jasná data o účinnosti této léčby ze studií fáze III, pořád je řada otázek, na které známe jen částečnou či žádnou odpověď. Tento článek se snaží na některé z nich odpověď na podkladě současných poznatků.
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- Publikační typ
- abstrakt z konference MeSH
BACKGROUND/AIM: Targeted therapy has become increasingly important in treating lung adenocarcinoma, the most common subtype of lung cancer. Next-generation sequencing (NGS) enables precise identification of specific genetic alterations in individual tumor tissues, thereby guiding targeted therapy selection. This study aimed to analyze mutations present in adenocarcinoma tissues using NGS, assess the benefit of targeted therapy and evaluate the progress in availability of targeted therapies over last five years. PATIENTS AND METHODS: The study included 237 lung adenocarcinoma patients treated between 2018-2020. The Archer FusionPlex CTL panel was used for NGS analysis. RESULTS: Gene variants covered by the panel were detected in 57% patients and fusion genes in 5.9% patients. At the time of the study, 34 patients (14.3% of patients) were identified with a targetable variant. Twenty-five patients with EGFR variants, 8 patients with EML4-ALK fusion and one patient with CD74-ROS1 fusion received targeted therapy. Prognosis of patients at advanced stages with EGFR variants treated by tyrosine kinase inhibitors and patients with EML4-ALK fusion treated by alectinib was significantly favorable compared to patients without any targetable variant treated by chemotherapy (p=0.0172, p=0.0096, respectively). Based on treatment guidelines applicable in May 2023, the number of patients who could profit from targeted therapy would be 64 (27.0% of patients), this is an increase by 88% in comparison to recommendations valid in 2018-2020. CONCLUSION: As lung adenocarcinoma patients significantly benefit from targeted therapy, the assessment of mutational profiles using NGS could become a crucial approach in the routine management of oncological patients.
- MeSH
- adenokarcinom plic * farmakoterapie genetika MeSH
- erbB receptory genetika MeSH
- lidé MeSH
- mutace MeSH
- nádory plic * farmakoterapie genetika patologie MeSH
- protoonkogenní proteiny genetika MeSH
- tyrosinkinasové receptory genetika MeSH
- tyrosinkinasy genetika MeSH
- vysoce účinné nukleotidové sekvenování MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND/AIM: The aim of this study was to investigate possible association between adverse events of nivolumab therapy and the effectiveness of treatment in patients with non-small cell lung cancer (NSCLC). Focusing on serious adverse events (i.e., those of grade ≥3), we evaluated overall survival (OS), progression-free survival (PFS), as well as objective response rate (ORR) to treatment. PATIENTS AND METHODS: We retrospectively analyzed a set of patients from the TULUNG database of NSCLC treated with nivolumab in eight oncology centers. We evaluated OS data based upon this set. To reduce possible bias, we further evaluated a subgroup of patients treated at the University Hospital in Pilsen, where the occurrence of adverse events, PFS, and ORR were independently examined by two experienced physicians. Survival statistics were evaluated using the Kaplan-Meier method and Cox analysis. RESULTS: We observed significantly greater OS, PFS, and ORR in the group of patients experiencing adverse events upon nivolumab treatment versus in those patients without such events. Although the univariable model analyzing the data set of all patients demonstrated higher OS in patients with serious adverse events, only a nonsignificant trend was observed in the Cox multivariable model. In a subgroup of patients with PFS and ORR evaluation, we did observe significant, favorable effects for patients having had serious adverse effects. CONCLUSION: Patients experiencing severe adverse events show a tendency toward better OS, PFS, and ORR compared to patients without or having only mild adverse events with nivolumab treatment.
- Publikační typ
- časopisecké články MeSH
Operabilní nemalobuněčný plicní karcinom byl dlouhá léta spojen s vysokým procentem recidiv při omezené možnosti neo-/adjuvantní léčby v podobě samotné chemoterapie. V posledních letech byl však na tomto poli zaznamenán velký rozvoj. První studie fáze III přinesly pozitivní data pro adjuvantní užití osimertinibu, atezolizumabu a pembrolizumabu. Další pozitivní výsledky přineslo i neoadjuvantní užití nivolumabu spolu s chemoterapií a perioperační přístup s pembrolizumabem a chemoterapií. Cílem tohoto článku je proto přinést souhrn změn a nových poznatků v této oblasti a poukázat i na některé výzvy, kterým nadále čelíme.
For many years, operable non-small cell lung cancer has been associated with a high percentage of recurrences with a limited possibility of neo-/adjuvant treatment in the form of chemotherapy alone. However, recent years have seen great development in this field. The first phase III studies yielded positive data for the adjuvant use of osimertinib, atezolizumab and pembrolizumab. Neoadjuvant use of nivolumab together with chemotherapy and perioperative approach with pembrolizumab and chemotherapy also brought other positive results. The aim of this article is therefore to bring a summary of the changes and new findings in this area and to point out some of the challenges we continue to face.
- Klíčová slova
- osimertinib, atezolizumab, pembrolizumab,
- MeSH
- adjuvantní chemoterapie metody MeSH
- anaplastická lymfomová kináza MeSH
- cílená molekulární terapie metody MeSH
- geny erbB-1 MeSH
- humanizované monoklonální protilátky aplikace a dávkování terapeutické užití MeSH
- imunoterapie metody MeSH
- inhibitory kontrolních bodů aplikace a dávkování terapeutické užití MeSH
- inhibitory tyrosinkinasy aplikace a dávkování terapeutické užití MeSH
- lidé MeSH
- nemalobuněčný karcinom plic * patologie terapie MeSH
- neoadjuvantní terapie metody MeSH
- nivolumab aplikace a dávkování terapeutické užití MeSH
- protinádorové látky imunologicky aktivní aplikace a dávkování terapeutické užití MeSH
- protinádorové látky aplikace a dávkování terapeutické užití MeSH
- protokoly protinádorové kombinované chemoterapie aplikace a dávkování terapeutické užití MeSH
- Check Tag
- lidé MeSH
PURPOSE: The aim of our study was to evaluate if therapeutic success in the first-line of anticancer treatments in patients with NSCLC may predict treatment success in the following lines. METHODS: We analyzed the data of patients with NSCLC stage III/IV from the TULUNG registry separately for chemotherapy, TKIs, ALK inhibitors, and immunotherapy in the first line during the years 2011-2019. "Succesful treatment " was defined as PFS ≥ 6 months, a "good responder " was a patient with ˃50% of "successful treatment " lines. Treatment responses were analyzed separately for each drug group. Descriptive statistics, Fisher exact test, Pearson Chi-Squared test, log-rank test, and univariate/multivariate logistic regression models were used. RESULTS: The first-line TKI therapy was successful in 66.2%, while good responders accounted for 50.7% of the cohort and their rates were similar for all types of TKIs. First-line platinum-based chemotherapy was successful in 43.1% and 48.6% for combinations with pemetrexed and bevacizumab, respectively. Good responders accounted for 29.5% and 25.9%, respectively. In the group of ALK inhibitors, we observed treatment success in 52.3% of cases, while alectinib showed the highest effectiveness (up to 70%). Good responders constituted 50% of the group. In the first-line immunotherapy group, survival benefit was observed in 52.3%, and good responders constituted 52.3% of the cohort. CONCLUSION: We concluded that the treatment success in first-line therapies in patients with NSCLC may predict survival benefits in the subsequent lines, particularly in EGFR- or ALK-positive disease and immunotherapy-treated patients.
BACKGROUND/AIM: Non-invasive circulating tumor biomarkers in liquid biopsy, such as microRNAs (miRNA), provide for better personalization of treatment strategies. The aim of our study was to assess the prognosis of patients with melanoma undergoing tumor resection with curative intent based on analysis of selected circulating miRNAs. PATIENTS AND METHODS: A total of 22 patients with stage I to III melanoma were enrolled into this prospective study. Plasma samples were obtained pre-surgery and early post-surgery from peripheral blood draws. A panel of 23 candidate miRNAs was designed and expression of miRNAs were analyzed by reverse transcription-quantitative polymerase chain reaction with exogenous reference control cel-miR-39-3p. RESULTS: Higher preoperative expression levels of miR-99a (p=0.008), miR-320 (p=0.009), miR-1908 (p=0.001), miR-494 (p=0.018) and miR-4487 (p=0.048) were associated with a shorter disease-free interval. Similarly, higher preoperative plasma levels of miR-99a (p=0.017), miR-221 (p=0.026), miR-320 (p=0.016), miR-494 (p=0.009), miR-1260 (p=0.026) and miR-1908 (p=0.024) were associated with worse overall survival. No significant differences between pre- and postoperative plasma miRNA levels were observed. CONCLUSION: Liquid biopsy is a minimally-invasive approach which can lead to a better understanding of cancer behavior and offers the possibility of precise patient prognosis, allowing selection of the most appropriate treatment. Our study showed that preoperative plasma levels of miR-99a, miR-221, miR-320, miR-494, miR-1908 and miR-4487 were associated with disease-free interval and overall survival of patients with early-stage melanoma. This approach may help in decision-making about the appropriateness of modern adjuvant treatment administration in patients with resectable melanoma.
