Background: Perioperative chemotherapy is a recommended treatment approach for localised oesophag... more Background: Perioperative chemotherapy is a recommended treatment approach for localised oesophago-gastric junction adenocarcinoma, but not all patients respond to neoadjuvant chemotherapy. Early identification of non-responders and treatment adaptation in the preoperative period could improve outcomes. GastroPET is a national, multicentre phase II trial evaluating a 18FDG-PET/CT-guided preoperative treatment strategy with the R0 resection rate as a primary endpoint. Here, we report on the accuracy of the methodology, the feasibility of the study design and patient safety data after enrolment of the first 63 patients. Methods: Patients with locally advanced oesophago-gastric junction adenocarcinoma (Siewert I – III) stage Ib–IIIc underwent baseline 18FDG-PET/CT scanning and re-evaluation after 14 days of oxaliplatinum-5FU-(docetaxel) chemotherapy. Responders were defined by a ⩾ 35% decrease in tumour FDG standardised uptake value (SUV)average from baseline. Responders continued with...
Malignant pleural mesothelioma (MPM) is the most frequent primary tumor of this anatomical struct... more Malignant pleural mesothelioma (MPM) is the most frequent primary tumor of this anatomical structure. It is usually caused by exposure to asbestos and the incidence continues to rise despite the fact that work with asbestos is banned in European countries. Presented is a set of data on consecutive patients treated with standard first-line cisplatin/pemetrexed chemotherapy in Czech centers. Another sample comprised patients receiving second-line pemetrexed therapy. Data from 2008-2018 were analyzed at the Institute of Biostatistics and Analyses in Brno. The study included 249 and 35 patients receiving first- A nd second-line therapy, respectively. There were 66 females and 183 males with a mean age of 64 years. Occupational and non-occupational exposure to asbestos was confirmed in 58 and 23 cases, respectively; no exposure was found in 168 patients. The most common histological types were epithelioid MPM in 167 patients, mixed in 26 and sarcomatoid in 16 patients; no histological ty...
Pěti leků (pemetrexed, erlotinib, bevacizumab, gefinitib a afatinib) bylo použito jako prvni lecb... more Pěti leků (pemetrexed, erlotinib, bevacizumab, gefinitib a afatinib) bylo použito jako prvni lecby nemalobuněcneho karcinomu plic (NSCLC) u 2234 pacientů v Ceske republice v letech 2006 až 2017. Detailni morfologicka a geneticka analýza NSCLC byla k dispozici. Výsledky lecby jsou analyzovany.
Celkova incidence NSCLC v CR kolisa, ve srovnani let 2003-2013 vzrostla o 11 %, pokud jde o trend... more Celkova incidence NSCLC v CR kolisa, ve srovnani let 2003-2013 vzrostla o 11 %, pokud jde o trend poslednich pěti iet, růst je již jen na urovni 0,4%. Před rokem 1980 byl pokrocilý NSCLC považovan za nador, který chemoterapii odolava. Na přelomu tisicileti se median přežiti nemocných s pokrocilým NSCLC pohyboval v rozmezi 8-10 měsiců. V poslednich letech dochazi k jeho prodlouženi.
Ve srovnani s daty zpracovanými na zakladě udajů do 26.3.2012 je v 1. linii lecby NSCLC evidentni... more Ve srovnani s daty zpracovanými na zakladě udajů do 26.3.2012 je v 1. linii lecby NSCLC evidentni narůst nemocných lecených pemetrexedem, prakticky nenarůsta pocet v 1. linii lecených erlotinibem. Narůst lecených gefitinibem svědci o tom, že ve vysetřovani aktivacnich mutaci genu EGFR jsou výrazne rezervy. Narůst lecených bevacizumabem je rovněž malý, ale zlepseni lze ocekavat v průběhu roku 2013, protože v některých pneumoonkologických centrech je bavcizumab hrazen mezi centrovými leky, což do konce roku 2012 nebylo.
Per literature, patients with epidermal growth factor receptor (EGFR) exon-20 insertions respond ... more Per literature, patients with epidermal growth factor receptor (EGFR) exon-20 insertions respond poorly to tyrosine kinase inhibitors (TKIs). This study analyzed real-world data to examine the prognostic and predictive value of these mutations. We conducted a retrospective cohort study using Czech TULUNG Registry data, with data on multiple mutation types, collected in 2011-2020. We analyzed 554 (95.85%) patients with EGFR exon-19 deletions or exon-21 L858R substitutions and 24 (4.15%) patients with exon-20 insertions who received first-line high-value therapies. We summarized clinical characteristics and outcomes in all patients and by cohort. The risk of progression was statistically significantly higher (86%) in the exon-20 insertion cohort compared to the cohort with other mutations. Although not statistically significant, the risk of death was 44% higher in patients with exon-20 insertions. Advanced NSCLC patients with rare EGFR exon-20 insertions have a high risk of progression.
BACKGROUND First-line durvalumab plus etoposide with either cisplatin or carboplatin (platinum-et... more BACKGROUND First-line durvalumab plus etoposide with either cisplatin or carboplatin (platinum-etoposide) showed a significant improvement in overall survival versus platinum-etoposide alone in patients with extensive-stage small-cell lung cancer (ES-SCLC) in the CASPIAN study. Here we report updated results, including the primary analysis for overall survival with durvalumab plus tremelimumab plus platinum-etoposide versus platinum-etoposide alone. METHODS CASPIAN is an ongoing, open-label, sponsor-blind, randomised, controlled phase 3 trial at 209 cancer treatment centres in 23 countries worldwide. Eligible patients were aged 18 years or older (20 years in Japan) and had treatment-naive, histologically or cytologically documented ES-SCLC, with a WHO performance status of 0 or 1. Patients were randomly assigned (1:1:1) in blocks of six, stratified by planned platinum, using an interactive voice-response or web-response system to receive intravenous durvalumab plus tremelimumab plus platinum-etoposide, durvalumab plus platinum-etoposide, or platinum-etoposide alone. In all groups, patients received etoposide 80-100 mg/m2 on days 1-3 of each cycle with investigator's choice of either carboplatin area under the curve 5-6 mg/mL/min or cisplatin 75-80 mg/m2 on day 1 of each cycle. Patients in the platinum-etoposide group received up to six cycles of platinum-etoposide every 3 weeks and optional prophylactic cranial irradiation (investigator's discretion). Patients in the immunotherapy groups received four cycles of platinum-etoposide plus durvalumab 1500 mg with or without tremelimumab 75 mg every 3 weeks followed by maintenance durvalumab 1500 mg every 4 weeks. The two primary endpoints were overall survival for durvalumab plus platinum-etoposide versus platinum-etoposide and for durvalumab plus tremelimumab plus platinum-etoposide versus platinum-etoposide in the intention-to-treat population. Safety was assessed in all patients who received at least one dose of study treatment. This study is registered at ClinicalTrials.gov, NCT03043872. FINDINGS Between March 27, 2017, and May 29, 2018, 972 patients were screened and 805 were randomly assigned (268 to durvalumab plus tremelimumab plus platinum-etoposide, 268 to durvalumab plus platinum-etoposide, and 269 to platinum-etoposide). As of Jan 27, 2020, the median follow-up was 25·1 months (IQR 22·3-27·9). Durvalumab plus tremelimumab plus platinum-etoposide was not associated with a significant improvement in overall survival versus platinum-etoposide (hazard ratio [HR] 0·82 [95% CI 0·68-1·00]; p=0·045); median overall survival was 10·4 months (95% CI 9·6-12·0) versus 10·5 months (9·3-11·2). Durvalumab plus platinum-etoposide showed sustained improvement in overall survival versus platinum-etoposide (HR 0·75 [95% CI 0·62-0·91]; nominal p=0·0032); median overall survival was 12·9 months (95% CI 11·3-14·7) versus 10·5 months (9·3-11·2). The most common any-cause grade 3 or worse adverse events were neutropenia (85 [32%] of 266 patients in the durvalumab plus tremelimumab plus platinum-etoposide group, 64 [24%] of 265 patients in the durvalumab plus platinum-etoposide group, and 88 [33%] of 266 patients in the platinum-etoposide group) and anaemia (34 [13%], 24 [9%], and 48 [18%]). Any-cause serious adverse events were reported in 121 (45%) patients in the durvalumab plus tremelimumab plus platinum-etoposide group, 85 (32%) in the durvalumab plus platinum-etoposide group, and 97 (36%) in the platinum-etoposide group. Treatment-related deaths occurred in 12 (5%) patients in the durvalumab plus tremelimumab plus platinum-etoposide group (death, febrile neutropenia, and pulmonary embolism [n=2 each]; enterocolitis, general physical health deterioration and multiple organ dysfunction syndrome, pneumonia, pneumonitis and hepatitis, respiratory failure, and sudden death [n=1 each]), six (2%) patients in the durvalumab plus platinum-etoposide group (cardiac arrest, dehydration, hepatotoxicity, interstitial lung disease, pancytopenia, and sepsis [n=1 each]), and two (1%) in the platinum-etoposide group (pancytopenia and thrombocytopenia [n=1 each]). INTERPRETATION First-line durvalumab plus platinum-etoposide showed sustained overall survival improvement versus platinum-etoposide but the addition of tremelimumab to durvalumab plus platinum-etoposide did not significantly improve outcomes versus platinum-etoposide. These results support the use of durvalumab plus platinum-etoposide as a new standard of care for the first-line treatment of ES-SCLC. FUNDING AstraZeneca.
ABSTRACT Background Clinical trials in advanced renal cell carcinoma (RCC) tend to exclude patien... more ABSTRACT Background Clinical trials in advanced renal cell carcinoma (RCC) tend to exclude patients (pts) with brain metastases (mets). We report safety and efficacy outcomes from a subanalysis of PREDICT (NCT 00895674), a large, non-interventional study of sorafenib in pts with advanced RCC, according to sites of mets. Table: 817P Metastases subsets Event Brain (n = 121) Bone (n = 673) Lung, all (n = 1723) Lung, only (n = 779) Overall (n = 2599) Any AE 77 (63.6) 401 (59.6) 1011 (58.7) 406 (52.1) 1479 (56.9) Any drug-related AE 58 (47.9) 316 (47.0) 861 (50.0) 366 (47.0) 1240 (47.7) Any SAE 39 (32.2) 156 (23.2) 297 (17.2) 90 (11.6) 477 (18.4) Any drug-related SAE 12 (9.9) 42 (6.2) 89 (5.2) 30 (3.9) 140 (5.4) Most frequent any grade drug-related AEs* Hand–foot skin reaction 20 (16.5) 106 (15.8) 366 (21.2) 188 (24.1) 520 (20.0) Diarrhea 19 (15.7) 111 (16.5) 306 (17.8) 114 (14.6) 443 (17.1) Rash† 8 (6.6) 58 (8.6) 155 (9.0) 65 (8.3) 220 (8.5) Alopecia 5 (4.1) 36 (5.4) 96 (5.6) 44 (5.7) 145 (5.6) Decreased appetite 7 (5.8) 24 (3.6) 44 (2.6) 12 (1.5) 76 (2.9) Methods Pts were eligible based on a diagnosis of advanced RCC and a decision by the investigator to prescribe sorafenib under compliance of the local product label. Physician assessments of efficacy and tolerability were collected for up to 12 months. Results Of the efficacy population (n = 2311), 1079 pts (47%) had mets in >1 organ. Sites included bone (n = 635), brain (n = 113), lung (n = 1639); 750 pts had mets only in the lung (‘lung only’). Baseline characteristics across disease-site subsets were: 69–74% male; 73–82% aged 1 site (6.2 months). Median DOT was longest in pts with lung only mets (9.1 months); in the other subsets it was numerically similar to overall median DOT (brain, 7.0 months; bone, 6.4 months; lung, 7.5 months). Sorafenib was generally well tolerated (Table). Serious adverse event rates were numerically higher in pts with brain mets vs the other subsets, but no cerebrovascular events were reported. Conclusions In pts with RCC treated in clinical practice, sorafenib DOT was >6 months regardless of number or location of metastases, and sorafenib was generally well tolerated regardless of disease site. Number (%) patients with AEs (safety population). Disclosure J. Mardiak: Jozef Mardiak has received Research Grants from Novartis and has received honoraria from Pfizer and Pierre Fabre. J. Ma: Jianhui Ma has received Research Grants from Bayer. M. Zemanova: Milada Zemanova has received consulting and lecture fees from Glaxo Smith Kline and Roche. N. Leonhartsberger: Nicolai Leonhartsberger has received honoraria from Bayer, Pfizer and Roche. K. Stauch: Kathrin Stauch is an employee of Bayer HealthCare and owns stock in Bayer Pharma AG. A. Boeckenhoff: Annette Boeckenhoff is an employee of Bayer HealthCare and owns stock in Bayer Pharma AG. J. Yu: Jian Yu is an employee of Bayer HealthCare. B. Escudier: Bernard Escudier has served in an advisory role for Pfizer, Novartis, Roche, GSK, Bayer and Aveo, and has received honoraria from Pfizer, Novartis, Roche, GSK, Bayer and Aveo. D. Jager: Dirk Jager has received honoraria from Bayer, Amgen, Pfizer, Novartis, Roche, Fresenius Kabi and Hoffmann-La Roche. All other authors have declared no conflicts of interest.
Although a significant proportion of patients with metastatic renal cell carcinoma (mRCC) are eld... more Although a significant proportion of patients with metastatic renal cell carcinoma (mRCC) are elderly, the data on the outcomes of targeted therapies in this population are limited. The aim of the present retrospective registry-based study was to analyse efficacy and toxicity of sunitinib as the first-line targeted therapy of elderly mRCC patients. The national RENal information system registry of mRCC patients treated with targeted agents in the Czech Republic was used as the data source. Of the 1315 patients treated with sunitinib as first-line targeted therapy, 1016 and 299 patients were aged <70 and ≥70 years, respectively. Elderly patients had a significantly longer interval from diagnosis to the initiation of therapy. Median progression-free survival was 10.8 months (95 % confidence interval 9.8-11.8) and 8.8 months (7.2-10.4) for patients aged <70 and ≥70 years, respectively (p = 0.321). Median overall survival was 31.9 months (27.9-35.9) and 26.3 months (21.3-31.2), respectively (p = 0.044). Significantly more elderly patients started on a reduced dose of sunitinib or discontinued the treatment prior to progression because of adverse events. The differences in patient profile and dose-reduction rates point to a different approach in the management of older and younger patients in daily clinical practice. The lower dose intensity of sunitinib in the elderly population may have translated into inferior survival.
Karcinom jicnu je onemocněni s 90% mortalitou, ale cast pacientů s lokalně pokrocilým onemocněnim... more Karcinom jicnu je onemocněni s 90% mortalitou, ale cast pacientů s lokalně pokrocilým onemocněnim může dlouhodobě přeživat diky multidisciplinarni lecbě. Dokladem je tato kazuistika 40leteho muže s dlaždicovým karcinomem středniho jicnu prorůstajicim do dýchacich cest ve stadiu T4N1M0. Prvnim lecebným zakrokem bylo zavedeni Dumon Y-stentu do dýchacich cest jako urgentni zabrana sufokace. V dalsim postupu byla použita konkomitantni chemoradioterapie, s davkou zařeni 66Gy/33 frakci/47 dni normofrakcionaci. Chemoterapie v kombinaci cisplatina a fluorouracil byla podavana v celkove delce 6 cyklů, s ozařenim během 2. a 3. cyklu. Na CT po lecbě byla zjistěna castecna regrese nadoru, endoskopicke biopsie z jicnu i průdusek byly negativni. V prvnim roce po chemoradioterapii bylo nutno řesit těsnou stenozu jicnu s přiznaky až uplne afagie, což se podařilo zvladnout dilatacemi. V dalsim obdobi stav nemocneho komplikovaly endobronchialni granulace řesene lokalnim osetřenim laserem a jejich mec...
Background The aim of this project was to collect real-world evidence and describe treatment patt... more Background The aim of this project was to collect real-world evidence and describe treatment patterns for stage III non-small cell lung cancer in Central and Eastern Europe. Based on real-world evidence, an expert opinion was developed, and the unmet needs and quality indicators were identified. Patients and methods A systematic literature search and a multidisciplinary expert panel of 10 physicians from 7 countries used a modified Delphi process to identify quality indicators and unmet needs in patients with stage III non-small cell lung cancer. The profound questionnaire was used to characterize treatment patterns used for stage III non-small cell lung cancer, and a systematic review identified patterns in Central and Eastern Europe. The first questionnaire was completed by a group of medical oncologists, radiation oncologists and pneumologists. The panel of experts attended an in-person meeting to review the results of the questionnaire and to process a second round Delphi. An ad...
Background Management of non-small-cell lung cancer (NSCLC) is affected by regional specificities... more Background Management of non-small-cell lung cancer (NSCLC) is affected by regional specificities. The present study aimed at determining diagnostic and therapeutic procedures including outcome of patients with NSCLC stage III in the real-world setting in Central European countries to define areas for improvements . Patients and methods This multicentre, prospective and non-interventional study collected data of patients with NSCLC stage III in a web-based registry and analysed them centrally. Results Between March 2014 and March 2017, patients (n=583) with the following characteristics were entered: 32% females, 7% never-smokers; ECOG performance status (PS) 0, 1, 2 and 3 in 25%, 58%, 12% and 5%, respectively; 21% prior weight loss; 53% squamous carcinoma, 38% adenocarcinoma; 10% EGFR mutations. Staging procedures included chest X-ray (97% of patients), chest CT (96%), PET-CT (27%), brain imaging (20%), bronchoscopy (89%), endobronchial ultrasound (EBUS) (13%) and CT-guided biopsy ...
Background Treatment of non-small cell lung carcinoma (NSCLC) stage III remains a challenge. Both... more Background Treatment of non-small cell lung carcinoma (NSCLC) stage III remains a challenge. Both local relapses and distant metastases are frequent, with 5-year survival often less than 20%. Management of locally advanced NSCLC represents a broad spectrum of treatment modalities combinations. There is evidence that management of stage III NSCLC varies between different countries and centres according to regional standards, facilities and resources. The aim of the study is to determine the actual standard management (diagnostic and therapeutic procedures) of patients with stage III NSCLC in Central European centres/countries.
Plicni karcinom je hlavni přicinou umrti na rakovinu a větsina nemocných přichazi s metastatickým... more Plicni karcinom je hlavni přicinou umrti na rakovinu a větsina nemocných přichazi s metastatickým stadiem IV. Terapie v tomto stadiu spociva hlavně v paliativni systemove lecbě. V soucasnosti existuji rozdilne lecebne přistupy podle dlaždicove nebo non-squamozni diferenciace a podle molekularně genetických vlastnosti. Standardem by mělo být vysetřeni molekularniho profilu EGFR aktivacnich mutaci a ALK translokace u vsech pacientů s non-squamozni histologii jestě před zahajenim lecby. V připadě citlivých mutaci vede cilena lecba TK inhibitorem (erlotinib, gefitinib, afatinib) nebo crizotinibem a v druhe linii nyni ceritinibem k dosaženi přibližně 60 % lecebných odpovědi a významně prodlužuje přežiti. Dvojkombinace cytostatik založene na platinovem derivatu jsou obvykle pro ostatni pacienty. U non-squamoznich nadorů je vhodne přidat k chemoterapii bevacizumab, pokud nejsou kontraindikace teto lecby. Pro nemocne lecene v prvni linii platinovou kombinaci je možne podavat udržovaci lecbu...
Význam chemoterapie u karcinomu jicnu spociva v jejim zařazeni do kombinovane lecby lokalizovanýc... more Význam chemoterapie u karcinomu jicnu spociva v jejim zařazeni do kombinovane lecby lokalizovaných stadii, nebo ji lze podat jako paliativni lecbu. U metastazujiciho dlaždicoveho karcinomu je přinos chemoterapie pro prodlouženi života nejistý, u adenokarcinomů je prokazan prospěch několika měsiců. Chemoterapii zde indikujeme u pacientů v dobrem stavu, s aktivnim přistupem k terapii, věk nad 70 let neni kontraindikaci. Doporuceny jsou kombinace založene na cisplatině a 5-fluorouracilu. Jsou znama data podporujici podavani stejneho režimu u dlaždicových karcinomů jako u adenokarcinomů. Nově byly publikovany studie faze III dokladajici prospěch kombinaci s docetaxelem, oxaliplatinou a kapecitabinem. U dlaždicových karcinomů nebyl prokazan prospěch předoperacni ani pooperacni chemoterapie. U adenokarcinomů prodlužuje přežiti předoperacni podani 2–3 cyklů nebo perioperacni chemoterapie 3 cykly před a 3 cykly po operaci. Při neoperacni lecbě prodloužila konkomitantni chemoradioterapie 1le...
Background: Perioperative chemotherapy is a recommended treatment approach for localised oesophag... more Background: Perioperative chemotherapy is a recommended treatment approach for localised oesophago-gastric junction adenocarcinoma, but not all patients respond to neoadjuvant chemotherapy. Early identification of non-responders and treatment adaptation in the preoperative period could improve outcomes. GastroPET is a national, multicentre phase II trial evaluating a 18FDG-PET/CT-guided preoperative treatment strategy with the R0 resection rate as a primary endpoint. Here, we report on the accuracy of the methodology, the feasibility of the study design and patient safety data after enrolment of the first 63 patients. Methods: Patients with locally advanced oesophago-gastric junction adenocarcinoma (Siewert I – III) stage Ib–IIIc underwent baseline 18FDG-PET/CT scanning and re-evaluation after 14 days of oxaliplatinum-5FU-(docetaxel) chemotherapy. Responders were defined by a ⩾ 35% decrease in tumour FDG standardised uptake value (SUV)average from baseline. Responders continued with...
Malignant pleural mesothelioma (MPM) is the most frequent primary tumor of this anatomical struct... more Malignant pleural mesothelioma (MPM) is the most frequent primary tumor of this anatomical structure. It is usually caused by exposure to asbestos and the incidence continues to rise despite the fact that work with asbestos is banned in European countries. Presented is a set of data on consecutive patients treated with standard first-line cisplatin/pemetrexed chemotherapy in Czech centers. Another sample comprised patients receiving second-line pemetrexed therapy. Data from 2008-2018 were analyzed at the Institute of Biostatistics and Analyses in Brno. The study included 249 and 35 patients receiving first- A nd second-line therapy, respectively. There were 66 females and 183 males with a mean age of 64 years. Occupational and non-occupational exposure to asbestos was confirmed in 58 and 23 cases, respectively; no exposure was found in 168 patients. The most common histological types were epithelioid MPM in 167 patients, mixed in 26 and sarcomatoid in 16 patients; no histological ty...
Pěti leků (pemetrexed, erlotinib, bevacizumab, gefinitib a afatinib) bylo použito jako prvni lecb... more Pěti leků (pemetrexed, erlotinib, bevacizumab, gefinitib a afatinib) bylo použito jako prvni lecby nemalobuněcneho karcinomu plic (NSCLC) u 2234 pacientů v Ceske republice v letech 2006 až 2017. Detailni morfologicka a geneticka analýza NSCLC byla k dispozici. Výsledky lecby jsou analyzovany.
Celkova incidence NSCLC v CR kolisa, ve srovnani let 2003-2013 vzrostla o 11 %, pokud jde o trend... more Celkova incidence NSCLC v CR kolisa, ve srovnani let 2003-2013 vzrostla o 11 %, pokud jde o trend poslednich pěti iet, růst je již jen na urovni 0,4%. Před rokem 1980 byl pokrocilý NSCLC považovan za nador, který chemoterapii odolava. Na přelomu tisicileti se median přežiti nemocných s pokrocilým NSCLC pohyboval v rozmezi 8-10 měsiců. V poslednich letech dochazi k jeho prodlouženi.
Ve srovnani s daty zpracovanými na zakladě udajů do 26.3.2012 je v 1. linii lecby NSCLC evidentni... more Ve srovnani s daty zpracovanými na zakladě udajů do 26.3.2012 je v 1. linii lecby NSCLC evidentni narůst nemocných lecených pemetrexedem, prakticky nenarůsta pocet v 1. linii lecených erlotinibem. Narůst lecených gefitinibem svědci o tom, že ve vysetřovani aktivacnich mutaci genu EGFR jsou výrazne rezervy. Narůst lecených bevacizumabem je rovněž malý, ale zlepseni lze ocekavat v průběhu roku 2013, protože v některých pneumoonkologických centrech je bavcizumab hrazen mezi centrovými leky, což do konce roku 2012 nebylo.
Per literature, patients with epidermal growth factor receptor (EGFR) exon-20 insertions respond ... more Per literature, patients with epidermal growth factor receptor (EGFR) exon-20 insertions respond poorly to tyrosine kinase inhibitors (TKIs). This study analyzed real-world data to examine the prognostic and predictive value of these mutations. We conducted a retrospective cohort study using Czech TULUNG Registry data, with data on multiple mutation types, collected in 2011-2020. We analyzed 554 (95.85%) patients with EGFR exon-19 deletions or exon-21 L858R substitutions and 24 (4.15%) patients with exon-20 insertions who received first-line high-value therapies. We summarized clinical characteristics and outcomes in all patients and by cohort. The risk of progression was statistically significantly higher (86%) in the exon-20 insertion cohort compared to the cohort with other mutations. Although not statistically significant, the risk of death was 44% higher in patients with exon-20 insertions. Advanced NSCLC patients with rare EGFR exon-20 insertions have a high risk of progression.
BACKGROUND First-line durvalumab plus etoposide with either cisplatin or carboplatin (platinum-et... more BACKGROUND First-line durvalumab plus etoposide with either cisplatin or carboplatin (platinum-etoposide) showed a significant improvement in overall survival versus platinum-etoposide alone in patients with extensive-stage small-cell lung cancer (ES-SCLC) in the CASPIAN study. Here we report updated results, including the primary analysis for overall survival with durvalumab plus tremelimumab plus platinum-etoposide versus platinum-etoposide alone. METHODS CASPIAN is an ongoing, open-label, sponsor-blind, randomised, controlled phase 3 trial at 209 cancer treatment centres in 23 countries worldwide. Eligible patients were aged 18 years or older (20 years in Japan) and had treatment-naive, histologically or cytologically documented ES-SCLC, with a WHO performance status of 0 or 1. Patients were randomly assigned (1:1:1) in blocks of six, stratified by planned platinum, using an interactive voice-response or web-response system to receive intravenous durvalumab plus tremelimumab plus platinum-etoposide, durvalumab plus platinum-etoposide, or platinum-etoposide alone. In all groups, patients received etoposide 80-100 mg/m2 on days 1-3 of each cycle with investigator's choice of either carboplatin area under the curve 5-6 mg/mL/min or cisplatin 75-80 mg/m2 on day 1 of each cycle. Patients in the platinum-etoposide group received up to six cycles of platinum-etoposide every 3 weeks and optional prophylactic cranial irradiation (investigator's discretion). Patients in the immunotherapy groups received four cycles of platinum-etoposide plus durvalumab 1500 mg with or without tremelimumab 75 mg every 3 weeks followed by maintenance durvalumab 1500 mg every 4 weeks. The two primary endpoints were overall survival for durvalumab plus platinum-etoposide versus platinum-etoposide and for durvalumab plus tremelimumab plus platinum-etoposide versus platinum-etoposide in the intention-to-treat population. Safety was assessed in all patients who received at least one dose of study treatment. This study is registered at ClinicalTrials.gov, NCT03043872. FINDINGS Between March 27, 2017, and May 29, 2018, 972 patients were screened and 805 were randomly assigned (268 to durvalumab plus tremelimumab plus platinum-etoposide, 268 to durvalumab plus platinum-etoposide, and 269 to platinum-etoposide). As of Jan 27, 2020, the median follow-up was 25·1 months (IQR 22·3-27·9). Durvalumab plus tremelimumab plus platinum-etoposide was not associated with a significant improvement in overall survival versus platinum-etoposide (hazard ratio [HR] 0·82 [95% CI 0·68-1·00]; p=0·045); median overall survival was 10·4 months (95% CI 9·6-12·0) versus 10·5 months (9·3-11·2). Durvalumab plus platinum-etoposide showed sustained improvement in overall survival versus platinum-etoposide (HR 0·75 [95% CI 0·62-0·91]; nominal p=0·0032); median overall survival was 12·9 months (95% CI 11·3-14·7) versus 10·5 months (9·3-11·2). The most common any-cause grade 3 or worse adverse events were neutropenia (85 [32%] of 266 patients in the durvalumab plus tremelimumab plus platinum-etoposide group, 64 [24%] of 265 patients in the durvalumab plus platinum-etoposide group, and 88 [33%] of 266 patients in the platinum-etoposide group) and anaemia (34 [13%], 24 [9%], and 48 [18%]). Any-cause serious adverse events were reported in 121 (45%) patients in the durvalumab plus tremelimumab plus platinum-etoposide group, 85 (32%) in the durvalumab plus platinum-etoposide group, and 97 (36%) in the platinum-etoposide group. Treatment-related deaths occurred in 12 (5%) patients in the durvalumab plus tremelimumab plus platinum-etoposide group (death, febrile neutropenia, and pulmonary embolism [n=2 each]; enterocolitis, general physical health deterioration and multiple organ dysfunction syndrome, pneumonia, pneumonitis and hepatitis, respiratory failure, and sudden death [n=1 each]), six (2%) patients in the durvalumab plus platinum-etoposide group (cardiac arrest, dehydration, hepatotoxicity, interstitial lung disease, pancytopenia, and sepsis [n=1 each]), and two (1%) in the platinum-etoposide group (pancytopenia and thrombocytopenia [n=1 each]). INTERPRETATION First-line durvalumab plus platinum-etoposide showed sustained overall survival improvement versus platinum-etoposide but the addition of tremelimumab to durvalumab plus platinum-etoposide did not significantly improve outcomes versus platinum-etoposide. These results support the use of durvalumab plus platinum-etoposide as a new standard of care for the first-line treatment of ES-SCLC. FUNDING AstraZeneca.
ABSTRACT Background Clinical trials in advanced renal cell carcinoma (RCC) tend to exclude patien... more ABSTRACT Background Clinical trials in advanced renal cell carcinoma (RCC) tend to exclude patients (pts) with brain metastases (mets). We report safety and efficacy outcomes from a subanalysis of PREDICT (NCT 00895674), a large, non-interventional study of sorafenib in pts with advanced RCC, according to sites of mets. Table: 817P Metastases subsets Event Brain (n = 121) Bone (n = 673) Lung, all (n = 1723) Lung, only (n = 779) Overall (n = 2599) Any AE 77 (63.6) 401 (59.6) 1011 (58.7) 406 (52.1) 1479 (56.9) Any drug-related AE 58 (47.9) 316 (47.0) 861 (50.0) 366 (47.0) 1240 (47.7) Any SAE 39 (32.2) 156 (23.2) 297 (17.2) 90 (11.6) 477 (18.4) Any drug-related SAE 12 (9.9) 42 (6.2) 89 (5.2) 30 (3.9) 140 (5.4) Most frequent any grade drug-related AEs* Hand–foot skin reaction 20 (16.5) 106 (15.8) 366 (21.2) 188 (24.1) 520 (20.0) Diarrhea 19 (15.7) 111 (16.5) 306 (17.8) 114 (14.6) 443 (17.1) Rash† 8 (6.6) 58 (8.6) 155 (9.0) 65 (8.3) 220 (8.5) Alopecia 5 (4.1) 36 (5.4) 96 (5.6) 44 (5.7) 145 (5.6) Decreased appetite 7 (5.8) 24 (3.6) 44 (2.6) 12 (1.5) 76 (2.9) Methods Pts were eligible based on a diagnosis of advanced RCC and a decision by the investigator to prescribe sorafenib under compliance of the local product label. Physician assessments of efficacy and tolerability were collected for up to 12 months. Results Of the efficacy population (n = 2311), 1079 pts (47%) had mets in >1 organ. Sites included bone (n = 635), brain (n = 113), lung (n = 1639); 750 pts had mets only in the lung (‘lung only’). Baseline characteristics across disease-site subsets were: 69–74% male; 73–82% aged 1 site (6.2 months). Median DOT was longest in pts with lung only mets (9.1 months); in the other subsets it was numerically similar to overall median DOT (brain, 7.0 months; bone, 6.4 months; lung, 7.5 months). Sorafenib was generally well tolerated (Table). Serious adverse event rates were numerically higher in pts with brain mets vs the other subsets, but no cerebrovascular events were reported. Conclusions In pts with RCC treated in clinical practice, sorafenib DOT was >6 months regardless of number or location of metastases, and sorafenib was generally well tolerated regardless of disease site. Number (%) patients with AEs (safety population). Disclosure J. Mardiak: Jozef Mardiak has received Research Grants from Novartis and has received honoraria from Pfizer and Pierre Fabre. J. Ma: Jianhui Ma has received Research Grants from Bayer. M. Zemanova: Milada Zemanova has received consulting and lecture fees from Glaxo Smith Kline and Roche. N. Leonhartsberger: Nicolai Leonhartsberger has received honoraria from Bayer, Pfizer and Roche. K. Stauch: Kathrin Stauch is an employee of Bayer HealthCare and owns stock in Bayer Pharma AG. A. Boeckenhoff: Annette Boeckenhoff is an employee of Bayer HealthCare and owns stock in Bayer Pharma AG. J. Yu: Jian Yu is an employee of Bayer HealthCare. B. Escudier: Bernard Escudier has served in an advisory role for Pfizer, Novartis, Roche, GSK, Bayer and Aveo, and has received honoraria from Pfizer, Novartis, Roche, GSK, Bayer and Aveo. D. Jager: Dirk Jager has received honoraria from Bayer, Amgen, Pfizer, Novartis, Roche, Fresenius Kabi and Hoffmann-La Roche. All other authors have declared no conflicts of interest.
Although a significant proportion of patients with metastatic renal cell carcinoma (mRCC) are eld... more Although a significant proportion of patients with metastatic renal cell carcinoma (mRCC) are elderly, the data on the outcomes of targeted therapies in this population are limited. The aim of the present retrospective registry-based study was to analyse efficacy and toxicity of sunitinib as the first-line targeted therapy of elderly mRCC patients. The national RENal information system registry of mRCC patients treated with targeted agents in the Czech Republic was used as the data source. Of the 1315 patients treated with sunitinib as first-line targeted therapy, 1016 and 299 patients were aged <70 and ≥70 years, respectively. Elderly patients had a significantly longer interval from diagnosis to the initiation of therapy. Median progression-free survival was 10.8 months (95 % confidence interval 9.8-11.8) and 8.8 months (7.2-10.4) for patients aged <70 and ≥70 years, respectively (p = 0.321). Median overall survival was 31.9 months (27.9-35.9) and 26.3 months (21.3-31.2), respectively (p = 0.044). Significantly more elderly patients started on a reduced dose of sunitinib or discontinued the treatment prior to progression because of adverse events. The differences in patient profile and dose-reduction rates point to a different approach in the management of older and younger patients in daily clinical practice. The lower dose intensity of sunitinib in the elderly population may have translated into inferior survival.
Karcinom jicnu je onemocněni s 90% mortalitou, ale cast pacientů s lokalně pokrocilým onemocněnim... more Karcinom jicnu je onemocněni s 90% mortalitou, ale cast pacientů s lokalně pokrocilým onemocněnim může dlouhodobě přeživat diky multidisciplinarni lecbě. Dokladem je tato kazuistika 40leteho muže s dlaždicovým karcinomem středniho jicnu prorůstajicim do dýchacich cest ve stadiu T4N1M0. Prvnim lecebným zakrokem bylo zavedeni Dumon Y-stentu do dýchacich cest jako urgentni zabrana sufokace. V dalsim postupu byla použita konkomitantni chemoradioterapie, s davkou zařeni 66Gy/33 frakci/47 dni normofrakcionaci. Chemoterapie v kombinaci cisplatina a fluorouracil byla podavana v celkove delce 6 cyklů, s ozařenim během 2. a 3. cyklu. Na CT po lecbě byla zjistěna castecna regrese nadoru, endoskopicke biopsie z jicnu i průdusek byly negativni. V prvnim roce po chemoradioterapii bylo nutno řesit těsnou stenozu jicnu s přiznaky až uplne afagie, což se podařilo zvladnout dilatacemi. V dalsim obdobi stav nemocneho komplikovaly endobronchialni granulace řesene lokalnim osetřenim laserem a jejich mec...
Background The aim of this project was to collect real-world evidence and describe treatment patt... more Background The aim of this project was to collect real-world evidence and describe treatment patterns for stage III non-small cell lung cancer in Central and Eastern Europe. Based on real-world evidence, an expert opinion was developed, and the unmet needs and quality indicators were identified. Patients and methods A systematic literature search and a multidisciplinary expert panel of 10 physicians from 7 countries used a modified Delphi process to identify quality indicators and unmet needs in patients with stage III non-small cell lung cancer. The profound questionnaire was used to characterize treatment patterns used for stage III non-small cell lung cancer, and a systematic review identified patterns in Central and Eastern Europe. The first questionnaire was completed by a group of medical oncologists, radiation oncologists and pneumologists. The panel of experts attended an in-person meeting to review the results of the questionnaire and to process a second round Delphi. An ad...
Background Management of non-small-cell lung cancer (NSCLC) is affected by regional specificities... more Background Management of non-small-cell lung cancer (NSCLC) is affected by regional specificities. The present study aimed at determining diagnostic and therapeutic procedures including outcome of patients with NSCLC stage III in the real-world setting in Central European countries to define areas for improvements . Patients and methods This multicentre, prospective and non-interventional study collected data of patients with NSCLC stage III in a web-based registry and analysed them centrally. Results Between March 2014 and March 2017, patients (n=583) with the following characteristics were entered: 32% females, 7% never-smokers; ECOG performance status (PS) 0, 1, 2 and 3 in 25%, 58%, 12% and 5%, respectively; 21% prior weight loss; 53% squamous carcinoma, 38% adenocarcinoma; 10% EGFR mutations. Staging procedures included chest X-ray (97% of patients), chest CT (96%), PET-CT (27%), brain imaging (20%), bronchoscopy (89%), endobronchial ultrasound (EBUS) (13%) and CT-guided biopsy ...
Background Treatment of non-small cell lung carcinoma (NSCLC) stage III remains a challenge. Both... more Background Treatment of non-small cell lung carcinoma (NSCLC) stage III remains a challenge. Both local relapses and distant metastases are frequent, with 5-year survival often less than 20%. Management of locally advanced NSCLC represents a broad spectrum of treatment modalities combinations. There is evidence that management of stage III NSCLC varies between different countries and centres according to regional standards, facilities and resources. The aim of the study is to determine the actual standard management (diagnostic and therapeutic procedures) of patients with stage III NSCLC in Central European centres/countries.
Plicni karcinom je hlavni přicinou umrti na rakovinu a větsina nemocných přichazi s metastatickým... more Plicni karcinom je hlavni přicinou umrti na rakovinu a větsina nemocných přichazi s metastatickým stadiem IV. Terapie v tomto stadiu spociva hlavně v paliativni systemove lecbě. V soucasnosti existuji rozdilne lecebne přistupy podle dlaždicove nebo non-squamozni diferenciace a podle molekularně genetických vlastnosti. Standardem by mělo být vysetřeni molekularniho profilu EGFR aktivacnich mutaci a ALK translokace u vsech pacientů s non-squamozni histologii jestě před zahajenim lecby. V připadě citlivých mutaci vede cilena lecba TK inhibitorem (erlotinib, gefitinib, afatinib) nebo crizotinibem a v druhe linii nyni ceritinibem k dosaženi přibližně 60 % lecebných odpovědi a významně prodlužuje přežiti. Dvojkombinace cytostatik založene na platinovem derivatu jsou obvykle pro ostatni pacienty. U non-squamoznich nadorů je vhodne přidat k chemoterapii bevacizumab, pokud nejsou kontraindikace teto lecby. Pro nemocne lecene v prvni linii platinovou kombinaci je možne podavat udržovaci lecbu...
Význam chemoterapie u karcinomu jicnu spociva v jejim zařazeni do kombinovane lecby lokalizovanýc... more Význam chemoterapie u karcinomu jicnu spociva v jejim zařazeni do kombinovane lecby lokalizovaných stadii, nebo ji lze podat jako paliativni lecbu. U metastazujiciho dlaždicoveho karcinomu je přinos chemoterapie pro prodlouženi života nejistý, u adenokarcinomů je prokazan prospěch několika měsiců. Chemoterapii zde indikujeme u pacientů v dobrem stavu, s aktivnim přistupem k terapii, věk nad 70 let neni kontraindikaci. Doporuceny jsou kombinace založene na cisplatině a 5-fluorouracilu. Jsou znama data podporujici podavani stejneho režimu u dlaždicových karcinomů jako u adenokarcinomů. Nově byly publikovany studie faze III dokladajici prospěch kombinaci s docetaxelem, oxaliplatinou a kapecitabinem. U dlaždicových karcinomů nebyl prokazan prospěch předoperacni ani pooperacni chemoterapie. U adenokarcinomů prodlužuje přežiti předoperacni podani 2–3 cyklů nebo perioperacni chemoterapie 3 cykly před a 3 cykly po operaci. Při neoperacni lecbě prodloužila konkomitantni chemoradioterapie 1le...
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