Slovenske smernice sistemskega zdravljenja pljučnega raka 2017

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Priporočila za obravnavo bolnikov s pljučnim rakom

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Lung cancer - Slovenian clinical practice guidelines in systemic treatment 2017

Rak pljuč je najbolj pogost rak (če upoštevamo nemelanocitni rak kože) in smrt zaradi raka pljuč je najbolj pogost vzrok smrti zaradi raka na svetu. V Sloveniji je po pogostosti na 4. Mestu in najbolj pogost vzrok smrti zaradi raka. Slabo preživetje bolnikov z rakom pljuč (5 letno srednje preživetje je okoli 12 %) v preteklosti se z uporabo novih sistemskih zdravljen v zadnjem času izboljšuje. Sistemsko zdravljenje je pomemeben del zdravljenja raka pljuč v vseh stadijih bolezni in pri vseh patohistoloških podtipih. Sistemsko zdravljenje na osnovi platine po operaciji v sklopu adjuvantnega zdravljenja se priporoča pri večini bolnikov. Kemoterapija se uporabija sočasno sz radioterapijo pri lokalno napredovali bolezni. Sistemsko zdravljenje je osnova zdravljenja razširjene bolezni. Vrsta sistemskega zdravljnja je odvisna od patohistološkega podtipa, molekularne analize, starosti, splošnega stanja zmogljivosti, sočasnih obolenj in bolnikovih želja. Sistemsko terapijo naj bi prejeli vsi bolniki z razširjeno boleznijo s PS 0-2. Zaželjeno je, da se način zdravlejnja določi na multidisciplinarnem konziliju, izvaja pa specialist internist onkolog, z znanjem in izkušnjami glede sistemske terapije. Slovenske smernice obravnave pljučnega raka so bile zadnjič objavljene leta 2006. V pripravi so nove celostne smernice obravnave raka pljuč v Sloveniji. V članku predstavljamo posodobljenje smernice sistemskega zdravljenja, ki so plod sodelovanja strokovnjakov treh ustanov, ki se ukvarjajo s sistemskim zdravljenjem raka pljuč v Sloveniji: Onkološki inštitut Ljubljana, Univerzitetna klinika Golnik in Univerzitetni klinični center Maribor.Primary lung cancer is the most common malignancy after non-melanocytic skin cancer, and deaths from lung cancer exceed those from any other malignancy worldwide. In Slovenia, it is the fourth most common cancer in males and in females, and the leading cause of death due to cancer. The historically poor survival rates of lung cancer patients (5-year relative survival of approx. 12 %) are improving, mainly due to the introduction of novel systemic therapies in the treatment algorithms. Systemic treatment is an important part of treatment in all stages of the disease as well as in all pathohistological subtypes of lung cancer. In operable disease, adjuvant systemic therapy with platinum- based schemas is recommended for a vast majority of patients. In locoregional disease, chemotherapy is used as concomitant with radiotherapy. Systemic treatment is the cornerstone of treatment in metastatic disease. The treatment strategy should take into account factors like histology, molecular pathology, age, PS, co-morbidities and the patient’s preferences. Systemic therapy should be considered in all stage IV patients with PS 0-2. Treatment decisions should ideally be discussed within a multidisciplinary tumor board, while the systemic treatment has to be performed by a specialist highly educated and skilled in systemic treatment of cancer. Slovenian guidelines for diagnosis, treatment and follow up were last published in 2006. In near future, a new, updated version will be published. Hereby, we only present the updated guidelines for systemic treatment. These guidelines were developed in a collaboration of the specialists from three institutions: Institute of Oncology Ljubljana, University Clinic Golnik, and University Clinical Centre Maribor

Solid cancer patients achieve adequate immunogenicity and low rate of severe adverse events after SARS-CoV-2 vaccination

Background: SARS-CoV-2 vaccination in cancer patients is crucial to prevent severe COVID-19 disease course. Methods: This study assessed immunogenicity of cancer patients on active treatment receiving mRNA-based SARS-CoV-2 vaccine by detection of anti-SARS-CoV-2 S1 IgG antibodies in serum, before, after the first and second doses and 3 months after a complete primary course of vaccination. Results were compared with healthy controls. Results: Of 112 patients, the seroconversion rate was 96%. A significant reduction in antibody levels was observed 3 months after vaccination in patients receiving immune checkpoint inhibitors versus control participants (p < 0.001). Adverse events were mostly mild. Conclusion: Immunogenicity after mRNA-based vaccine in cancer patients is adequate but influenced by the type of anticancer therapy. Antibody levels decline after 3 months, and thus a third vaccination is warranted

Selpercatinib in RET fusion-positive non-small-cell lung cancer (SIREN) : a retrospective analysis of patients treated through an access program

Introduction: Rearranged during transfection (RET) gene fusions are rare genetic drivers in non-small cell lung cancer (NSCLC). Selective RET-inhibitors such as selpercatinib have shown therapeutic activity in early clinical trialshowever, their efficacy in the real-world setting is unknown. Methods: A retrospective efficacy and safety analysis was performed on data from RET fusio-%positive NSCLC patients who participated in a selpercatinib access program (named patient protocol) between August 2019 and January 2021. Results: Data from 50 patients with RET fusion-positive advanced NSCLC treated with selpercatinib at 27 centers in 12 countries was analyzed. Most patients were Non-Asian (90%), female (60%), never-smokers (74%), with a median age of 65 years (range, 38-89). 32% of the patients had known brain metastasis at the time of selpercatinib treatment. Overall, 13 patients were treatment-naïve, while 37 were pretreated with a median of three lines of therapy (range, 1-8). The objective response rate (ORR) was 68% [95% confidence interval (CI), 53-81] in the overall population. The disease control rate was 92%. The median progression-free survival was 15.6 months (95% CI, 8.8-22.4) after a median follow-up of 9 months. In patients with measurable brain metastases (n=8) intracranial ORR reached 100%. In total, 88% of patients experienced treatment-related adverse events (TRAEs), a large majority of them being grade 1 or 2. The most common grade >/=3 TRAEs were increased liver enzyme levels (in 10% of patients), prolonged QTc time (4%), abdominal pain (4%), hypertension (4%), and fatigue/asthenia (4%). None of patients discontinued selpercatinib treatment for safety reasons. No new safety concerns were observed, nor where there any treatment-related death. Conclusions: In this real-world setting, the selective RET-inhibitor selpercatinib demonstrated durable systemic and intracranial antitumor activity in RET fusion-positive NSCLC and was well tolerated

Real-world experience with capmatinib in MET exon 14-mutated non-small cell lung cancer (RECAP) : a retrospective analysis from an early access program

Background: Patients with non-small cell lung cancer (NSCLC) presenting with mesenchymal–epithelial transition (MET) exon 14 skipping mutation have an unfavorable prognosis with standard treatments. Capmatinib is a selective MET inhibitor, which showed promising efficacy in this patient population in early trials. Methods: We performed a retrospective, international, multicenter efficacy and safety analysis in patients with NSCLC treated with capmatinib in an early access program between March 2019 and December 2021. Results: Data from 81 patients with advanced MET exon 14 mutated NSCLC treated with capmatinib in first- or later-line therapy were analyzed. Median age was 77years (range, 48–91), 56% were women, 86% had stage IV disease, and 27% had brain metastases. For all patients, the objective response rate (ORR) to capmatinib was 58% (95% CI, 47–69), whereas it was 68% (95% CI, 50–82) in treatment-naïve and 50% (95% CI, 35–65) in pretreated patients. The median progression-free survival was 9.5months (95% CI, 4.7–14.3), whereas it was 10.6months (95% CI, 5.5–15.7) in first-line and 9.1months (95% CI, 3.1–15.1) in pretreated patients. After a median follow-up of 11.0months, the median overall survival was 18.2 months (95% CI, 13.2–23.1). In patients with measurable brain metastases (n=11), the intracranial ORR was 46% (95% CI, 17–77). Capmatinib showed a manageable safety profile. Grade⩾3 treatment-related adverse events included peripheral edema (13%), elevated creatinine (4%), and elevated liver enzymes (3%). Conclusion: In patients with MET exon 14 skipping mutation, capmatinib showed durable systemic and intracranial efficacy and a manageable safety profile. This analysis confirms previously reported phase II data in a real-world setting

Expression of FGFR1-4 in malignant pleural mesothelioma tissue and corresponding cell lines and its relationship to patient survival and FGFR inhibitor sensitivity

Malignant pleural mesothelioma (MPM) is a devastating malignancy with limited therapeutic options. Fibroblast growth factor receptors (FGFR) and their ligands were shown to contribute to MPM aggressiveness and it was suggested that subgroups of MPM patients could benefit from FGFR-targeted inhibitors. In the current investigation, we determined the expression of all four FGFRs (FGFR1-FGFR4) by immunohistochemistry in tissue samples from 94 MPM patients. From 13 of these patients, we were able to establish stable cell lines, which were subjected to FGFR1-4 staining, transcript analysis by quantitative RT-PCR, and treatment with the FGFR inhibitor infigratinib. While FGFR1 and FGFR2 were widely expressed in MPM tissue and cell lines, FGFR3 and FGFR4 showed more restricted expression. FGFR1 and FGFR2 showed no correlation with clinicopathologic data or patient survival, but presence of FGFR3 in 42% and of FGFR4 in 7% of patients correlated with shorter overall survival. Immunostaining in cell lines was more homogenous than in the corresponding tissue samples. Neither transcript nor protein expression of FGFR1-4 correlated with response to infigratinib treatment in MPM cell lines. We conclude that FGFR3 and FGFR4, but not FGFR1 or FGFR2, have prognostic significance in MPM and that FGFR expression is not suffcient to predict FGFR inhibitor response in MPM cell lines

Prognostic impact of PD-1 and PD-L1 expression in malignant pleural mesothelioma : an international multicenter study

Background: Programmed cell death 1/programmed death ligand 1 (PD-1/PD-L1) immune-checkpoint blockade is a promising new therapeutic strategy in cancer. However, expression patterns and prognostic significance of PD-L1 and PD-1 are still controversial in human malignant pleural mesothelioma (MPM). Methods: Formalin-fixed paraffin-embedded (FFPE) tumor samples from 203 MPM patients receiving standard treatment without immunotherapy were collected from 5 European centers. PD-L1 and PD-1 expression of tumor cells (TCs) and tumor-infiltrating lymphocytes (TILs) were measured by immunohistochemistry and correlated with clinical parameters and long-term outcome. Results: High (>10%) PD-L1 TC and PD-1 TILs expressions were found in 18 (8%) and 39 (24%) patients, respectively. PD-L1 was rarely expressed by TILs [>/=1%, n=13 (8%)>10%, n=1]. No significant associations were found between the PD-L1 or PD-1 expression of TCs or TILs and clinicopathological parameters such as stage or histological subtype. Notably, patients with high (>10%) TC-specific PD-L1 expression exhibited significantly worse median overall survival (OS) (6.3 vs. 15.1 months of those with low TC PD-L1 expressionHR: 2.51, P10%) proved to be an independent negative prognostic factor for OS (HR: 2.486, P=0.005). There was no significant correlation between PD-L1 or PD-1 expression of TILs and OS. Conclusions: In this multicenter cohort study, we demonstrate that high (>10%) PD-L1 expression of TCs independently predicts worse OS in MPM. Further studies are warranted to investigate the value of PD-L1/PD-1 expression as a marker for treatment response in MPM patients receiving immunotherapy