- MeSH
- antibakteriální látky terapeutické užití MeSH
- febrilní neutropenie vyvolaná chemoterapií diagnóza etiologie farmakoterapie prevence a kontrola MeSH
- lidé MeSH
- nádory plic * komplikace MeSH
- riziko MeSH
- syndrom systémové zánětlivé reakce diagnóza farmakoterapie MeSH
- zánět * etiologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
Amivantamab (Rybrevant©) je bispecifická monoklonální protilátka, blokující extracelulární domény receptoru mezenchymálně-epiteliální tranzice (mesenchymal-epitelial transition, MET) a receptoru epidermálního růstového faktoru (epidermal growth factor receptor, EGFR). Působí skrze narušení interakce mezi ligandem a receptorem a blokuje ligandem indukovanou fosforylaci EGFR a c-MET.1 Aktivační mutace EGFR představují řídicí mutaci v 10-15 % případů nemalobuněčného karcinomu plic v Evropě.2 S nasazením tyrosinkinázových inhibitorů třetí generace, zejména osimertinibu, do první linie léčby, se nejčastějším mechanismem rezistence stává amplifikace receptoru MET (15-22 %).3 Účinnost blokády různých mutací EGFR amivantamabem se liší v závislosti na potřebě či absenci potřeby dimerizace pro aktivní signalizaci mutovaného receptoru.4 K zesílení blokády non-dimerizujících mutací byl proto do uspořádání registrační studie MARIPOSA-2 zařazen tyrosinkinázový inhibitor EGFR třetí generace lazertinib.5 Ten však v České republice není dostupný. Na základě teoretické vědy je předpoklad možnosti jeho nahrazení jiným adekvátním tyrosinkinázovým inhibitorem. Prezentujeme případ pacientky s mutací EGFR - delecí v exonu 19, u které došlo k rozvoji získané rezistence na osimertinib pomocí amplifikace MET. Po selhání systémové chemoterapie bylo opět dosaženo léčebné odpovědi kombinací amivantamabu a osimertinibu.
Amivantamab (Rybrevant©) is a bispecific monoclonal antibody that blocks the extracellular domains of MET and EGFR receptors. It acts through disruption of ligand-receptor interaction and blocks ligand-induced phosphorylation of EGFR and c-MET.1 Activating EGFR mutations represent the driving mutation in 10-15% of non-small cell lung cancer cases in Europe.2 With the introduction of the 3rd generation tyrosine kinase inhibitors, especially osimertinib, into first-line therapy, MET receptor amplification becomes the most common mechanism of resistance (15-22%).3 The efficacy of blockade of different EGFR mutations varies depending on the need (or lack of need) of dimerization for active mutant receptor signalling.4 The 3rd generation EGFR tyrosine kinase inhibitor lazertinib was therefore included in the design of the MARIPOSA-2 registration study.5 Unfortunately, lazertinib is not available in the Czech Republic. However, based on theoretical science, it should be possible to replace lazertinib other adequate tyrosine kinase inhibitors. We present the case of a patient with EGFR exon 19 deletion mutation, who developed acquired resistance to osimertinib through MET amplification. After failure of systemic chemotherapy, a therapeutic response was again achieved with the combination of amivantamab and osimertinib.
Entrektinib (Rozlytrek©) je aktuálně jediný inhibitor mutované tyrosinkinázy ROS1 (a kináz NTRK a ALK) hrazený v České republice. Translokace ROS1 představuje řídicí mutaci u 1-2 % případů neskvamózního nemalobuněčného karcinomu plic (non-small cell lung cancer, NSCLC). Medián doby trvání léčebné odpovědi činí 20,5 měsíce. Rezistence na entrektinib je zprostředkována jak sekundárními mutacemi genu ROS1 (např G2032R), tak aktivací alternativních signálních drah (MET, KRAS aj.). Mezinárodní doporučené postupy NCCN aj. doporučují rebiopsii a cílení léčby na sekundární mutaci, v případě nemožnosti pak repotrektinib nebo lorlatinib jako lék druhé linie. Prezentujeme případ pacientky s ROS1 mutovaným NSCLC, u které se lorlatinibem podařilo dosáhnout znovu remise intrakraniálních metastáz.
Entrectinib (Rozlytrek©) is currently the only reimbursed inhibitor of mutated ROS1 tyrosine kinase (and NTRK and ALK kinases) in the Czech Republic. ROS1 translocation represents the driving mutation in 1-2 % of non-squamous non-small cell lung cancer (NSCLC). The median duration of response is 20.5 months. Resistance to entrectinib is mediated by both secondary mutations in the ROS1 gene (e.g. G2032R) and activation of alternative signalling pathways (MET, KRAS, etc.). International guidelines, like NCCN, recommend rebiopsy, identification and targeting of the secondary mutation, and in case of impossibility to do so, repotrectinib or lorlatinib as a second-line treatment. We present the case of a patient with ROS1 mutated NSCLC who achieved remission of intracranial metastases with lorlatinib.
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
Non-small cell lung cancer (NSCLC) is largely promoted by a multistep tumorigenesis process involving various genetic and epigenetic alterations, which essentially contribute to the high incidence of mortality among patients with NSCLC. Clinical observations revealed that NSCLC also co-opts a multifaceted immune checkpoint dysregulation as an important driving factor in NSCLC progression and development. For example, a deregulated PI3K/AKT/mTOR pathway has been noticed in 50-70% of NSCLC cases, primarily modulated by mutations in key oncogenes such as ALK, EGFR, KRAS, and others. Additionally, genetic association studies containing patient-specific factors and local reimbursement criteria expose/reveal mutations in EGFR/ALK/ROS/BRAF/KRAS/PD-L1 proteins to determine the suitability of available immunotherapy or tyrosine kinase inhibitor therapy. Thus, the expression of such checkpoints on tumors and immune cells is pivotal in understanding the therapeutic efficacy and has been extensively studied for NSCLC treatments. Therefore, this review summarizes current knowledge in NSCLC tumorigenesis, focusing on its genetic and epigenetic intricacies, immune checkpoint dysregulation, and the evolving landscape of targeted therapies. In the context of current and future therapies, we emphasize the significance of antibodies targeting PD-1/PD-L1 and CTLA-4 interactions as the primary therapeutic strategy for immune system reactivation in NSCLC. Other approaches involving the promising potential of nanobodies, probodies, affibodies, and DARPINs targeting immune checkpoints are also described; these are under active research or clinical trials to mediate immune regulation and reduce cancer progression. This comprehensive review underscores the multifaceted nature, current state and future directions of NSCLC research and treatment.
- MeSH
- antigeny CD274 metabolismus MeSH
- erbB receptory metabolismus MeSH
- fosfatidylinositol-3-kinasy metabolismus MeSH
- karcinogeneze MeSH
- lidé MeSH
- nádorová transformace buněk MeSH
- nádory plic * farmakoterapie genetika MeSH
- nemalobuněčný karcinom plic * farmakoterapie genetika MeSH
- protoonkogenní proteiny p21(ras) MeSH
- tyrosinkinasové receptory metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy 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.
Prezentuje kazuistiku pacientky s metachronní nádorovou duplicitou, která byla léčena durvalumabem v udržovací léčbě po konkomitantní chemoradioterapii nemalobuněčného karcinomu plic. Současně nabízíme krátký přehled informací o této monoklonální protilátce, která nedávno získala úhradu též v léčbě malobuněčného karcinomu plic, a nabízí tak zlepšení prognózy nemocných v obou indikacích.
This article presents a case report of a patient with metachronous tumor occurrence, who was treated with durvalumab as maintenance therapy following concomitant chemoradiotherapy for non-small cell lung cancer. Simultaneously, we offer a brief review of this monoclonal antibody, which has recently received approval for reimbursement also in the treatment of small cell lung cancer, thus offering an improved prognosis for patients in both indications.
- Klíčová slova
- durvalumab,
- MeSH
- diagnostické zobrazování metody MeSH
- lidé MeSH
- monoklonální protilátky * farmakologie terapeutické užití MeSH
- nádory vaječníků chirurgie farmakoterapie MeSH
- nemalobuněčný karcinom plic * diagnóza farmakoterapie MeSH
- senioři MeSH
- Check Tag
- lidé MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
- Publikační typ
- abstrakt z konference MeSH
