Novartis (Slovakia)

5056 Background: Pts with newly diagnosed advanced ovarian cancer generally receive platinum plus taxane therapy. For pts who do not respond or relapse within 6 months, outlook remains poor. Patupilone, a natural epothilone, is a microtubule-targeting cytotoxic that has demonstrated clinical activity in taxane-sensitive and -resistant tumors. In a phase I/II study, we are investigating the safety and efficacy of patupilone in pts with advanced ovarian cancer who had failed to respond to or had relapsed within 6 months of first-line platinum therapy. Methods: Pts receive patupilone at a starting dose of 6.5 mg/m2 via 10- to 20-min IV infusion once every 3 wk (q3w) with proactive diarrhea management. Results: To date, 31 pts have been enrolled in 9 cohorts receiving 6.5 (n = 3), 7.0 (n = 3), 7.5 (n = 3), 8.0 (n = 6), 8.5 (n = 3), 9.0 (n = 6), 9.5 (n = 3), 10.0 (n = 3), and 10.5 (n = 1) mg/m2 patupilone. Currently, 29 pts are eligible for assessment; 90% had received prior taxane therapy. DLTs were not reported until the 8.0- and 8.5-mg/m2 cohorts; 1 pt in each had grade (gr) 3 fatigue. Gr 4 serum uric acid, gr 3 hypomagnesemia, and gr 2 serum creatinine precipitated by surgical ileus were reported on day 21 of the first cycle by a pt enrolled in the 9.0-mg/m2 cohort. However, these toxicities were deemed unrelated to study drug, the cohort was expanded and no DLTs were reported. Dose escalation has continued to the ongoing 10.5-mg/m2 cohort. Gr 3 diarrhea, gr 3/4 fatigue/malaise, and gr 3 vomiting were reported in 17%, 14%, and 7% of pts, respectively. Eight (28%) pts had gr 1/2 neuropathy/paresthesia; 1 case became gr 3 in a heavily (19 platinum cycles) pretreated pt. Hematologic toxicity was uncommon and 3 pts had gr 1 alopecia. Of the 19 pts evaluable for tumor response by RECIST, 1 had CR, 1 had PR, and 7 had SD; 1 additional pt had CR based on ascites disappearance. Of the 24 pts who had increased CA-125 at baseline, 7 (29%) had a 50% reduction in CA-125 levels (2 confirmed, 5 unconfirmed). Conclusions: Preliminary data indicate that patupilone administered once q3w is safe and well tolerated. The MTD has not been reached; dose escalation continues. Preliminary antitumor response is promising in this previously treated platinum-resistant pt population. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis, Novartis Pharmaceuticals AG Novartis Novartis Novartis

PURPOSE: To evaluate the prevalence and epidemiological characteristics of diabetic retinopathy (DR) in Slovakian patients with Type 1 and 2 diabetes mellitus (DM) in the DIARET SK study. PATIENTS AND METHODS: An epidemiological multi-center survey that included 4,078 adult patients (aged ≥18 years) from 51 diabetologists and 47 ophthalmologists. Data were collected from February to December 2015. RESULTS: The final data set consisted of 4,014 patients; 3,700 were enrolled (Type 2 DM = 3,405, Type 1 DM = 295) using a quasi-random approach; 16 (Type 2 DM = 15, Type 1 DM = 1) patients in the pre-specified group had DM duration of <5 years with a history of DR while 298 patients (Type 2 DM = 204, Type 1 DM = 94) had DM duration of ≥ 20 years. The mean (standard deviation [SD]) age of patients at diagnosis for Types 2 and 1 DM was 53.4 (9.5) and 27.6 (12.9) years, respectively. The mean (SD) glycated hemoglobin (HbA1c) was 7.5 (1.4) and 8.5 (1.6) in Types 2 and 1 DM patients, respectively, whereas a slightly higher proportion of patients had >11.0 HbA1c in Type 1 DM (5.8%) than Type 2 (2.0%). The mean (SD) duration of Type 2 DM was shorter compared with Type 1 (7.5 [5.2] vs 10.3 [6.9] years). In Type 2 DM patients, there were 516 (15.5%) cases of DR, 19 (0.56%) of proliferative DR (PDR), and 106 (3.11%) of diabetic macular edema (DME). In Type 1 DM patients, there were 86 (29.15%) cases of DR, 10 (3.39%) PDR, and 12 (4.07%) DME. CONCLUSIONS: In Slovakian patients with DM, the duration of disease and higher HbA1c were the most prevalent factors that contributed to the development of DR and DME.

5563 Background: Patients with ovarian cancer that relapse or recur within 6 months after platinum plus taxane therapy have a poor prognosis. Patupilone, a natural epothilone isolated from myxobacterium, is a microtubule targeting agent that was found to be safe and well tolerated, with clinical activity in refractory or resistant ovarian cancer. Methods: Patients were treated with a dose of patupilone 10 mg/m 2 , given intravenously over 10–20 minutes once every 3 weeks, which was found safe in a previous phase I study. Results: Total 113 women enrolled and 112 were treated. The median age was 56 years (range 18–85 years), and 11 % had WHO Performance Status (PS) of 2. Most patients (104) had ovarian cancer, while 5 were peritoneal and 2 each of fallopian or other origin. All patients had received prior platinum and taxane, and 50% had progressed in less than 3 months after prior platinum therapy. Patients received a median of 4 cycles (range 1–16) of patupilone with median average dose per cycle of 9.97 mg/m 2 , resulting in a median dose intensity of 100%. The most common grade 3/4 toxicity was diarrhea (21%/3%), fatigue (10%/1%), intestinal obstruction (5%/3%), anorexia (5%/1%), and vomiting (8%/0%). About 38% patients developed neuropathy, which was mostly grade 1 (in 22%), with only 4% patients at grade 3. A total of 6 patients (5.4%) discontinued due to serious adverse event. There were 4 (3.6%) deaths on study, none of which were considered treatment related. The best overall response rate (by RECIST criteria) was 7.1% (95% CI: 3.0%, 14.0%) with no patient having complete response and 8 patients with partial response. Also, 46 patients (41%) had stable disease and 39 (34.8%) progressed, while response was unknown or could not be evaluated in 19 patients. The median PFS is 2.5 months (95% CI: 1.4, 3.5), and median overall survival is 11.2 months (95% CI: 8.3, 14.9), with 33% patients censored. Conclusions: Patupilone 10mg/m 2 administered at q3wk was safe and well tolerated. It showed promising activity in patients with refractory/resistant ovarian cancer. [Table: see text]

BACKGROUND: The CDK4/6 inhibitor, ribociclib in combination with endocrine therapy significantly improved progression-free survival in the first line setting in post-menopausal patients with HR+/HER2- advanced breast cancer (ABC) in a pivotal phase 3, placebo-controlled trial (MONALEESA-2) and demonstrated superior overall survival in premenopausal patients with HR+/HER2- ABC (MONALEESA-7). The multinational, phase 3b, CompLEEment-1 trial, which assessed the safety and efficacy of ribociclib plus letrozole in a broader population of patients who have not received prior endocrine therapy for advanced disease, is the largest phase 3 clinical trial to date to evaluate the safety and efficacy of a CDK4/6 inhibitor. We report a subanalysis of data from patients (N = 339) enrolled in the central and south European countries of the SERCE (Southern Europe, RUC, Central Europe) cluster of CompLEEment-1. PATIENTS AND METHODS: Men and women of any menopausal status with HR+/HER2- ABC received once-daily oral ribociclib 600 mg (3-weeks on/1-week-off), plus letrozole 2.5 mg continuously. Men/premenopausal women also received a GnRH-agonist. The primary outcome was the number of patients with adverse events (AEs) over a timeframe of approximately 36 months. Time-to-progression, overall response rate, and clinical benefit rate were also measured. RESULTS: Safety results in the SERCE subgroup were consistent with those in the pivotal clinical trials of ribociclib in combination with endocrine therapy. Treatment-related AEs leading to dose adjustments/interruption occurred in 63.1% of patients but led to treatment discontinuation in only 10.6%. The most common treatment-related AEs of grade ≥ 3 were neutropenia and transaminase elevations. There were no fatal treatment-related events. CONCLUSIONS: These findings from the SERCE subgroup support the safety and manageable tolerability of ribociclib in a broad range of patients with HR+/HER2- ABC more representative of patients in real-world clinical practice.

Introduction: Omalizumab was proven to be effective and safe in patients with moderate-to-severe allergic asthma. However, there is no direct evidence of the benefits of add-on omalizumab in real-life practice in the Slovakian population. Aim: This subgroup analysis assessed the real-life effectiveness and safety of omalizumab in Slovakian patients with severe allergic asthma enrolled in the eXpeRience registry. Material and methods: Patients who commenced omalizumab 15 weeks prior to inclusion were assessed for the physicians' global evaluation of treatment effectiveness (GETE), exacerbation rate, asthma symptoms, lung function, oral corticosteroid (OCS) use, rescue medication, hospitalizations, and school/work absenteeism at 16 weeks and 12 and 24 months. Results: Of 204 patients, 159 (77.9%) completed 2-year follow-up. As per GETE, 69.5% of patients treated with omalizumab achieved excellent/good response at 16 (±1) weeks. The proportion of patients with no severe clinically significant asthma exacerbations increased from 17.3% at pre-treatment to 82.4% and 92.0% at months 12 and 24, respectively. Maintenance OCS use was reduced to 17.0% and 15.3% of patients at 12 and 24 months, respectively, compared with 34.7% at baseline (BL). From BL until month 24, asthma control test scores improved from 11.6 to 20.3; rescue medication use/week decreased from 5.5 to 1.6 days; mean total number of days of asthma-related medical healthcare use decreased from 7.7 to 0.3 days and missed workdays decreased from 16.8 to 0.3 days. No new safety signals were observed. Conclusions: Add-on omalizumab was effective and well-tolerated in Slovakian patients, complementing the results observed in the overall population of eXpeRience.

Tinnitus is defined as a non-specific symptom characterized as buzzing, whistling, fizzing, ringing or sensing of wide frequency range and different intensity sounds in one or both ears. Tinnitus is a sensation of sound perceived by an individual in the absence of an external sound source. It affects approximately 15% of the population worldwide. Tinnitus is usually connected with many kinds of hearing disturbances, but it could be also a symptom of different other health problems. Metabolic syndrome and its components as arterial hypertension, diabetes mellitus, obesity and dyslipoproteinaemia with arteriosclerosis are important and frequent causes of tinnitus. Due to the high number of heterogeneous etiologic factors in subjective and objective tinnitus a complex approach in differential diagnosis is crucial. Tinnitus can be a concomitant symptom to many disorders of peripheral statoacoustic apparatus. It is necessary to distinguish whether tinnitus is an acute symptom in onset, e.g. in Meniere’s disease, acute trauma, inflammation of the inner ear, or it is a part of chronic disease otological in origin. Various cardiovascular diseases can be the cause of newly arisen or persistent tinnitus. Among the most important causes there is a reduced perfusion with ischemic changes. Vascular changes can be localized either extraor intracranially. Among them are stenosis of arteries, haemangioma and glomus caroticum tumours. Changes in the rheology of blood in anaemia or polycythemia can be the cause of tinnitus, as well. It is important to think also about vasculitis as a cause of tinnitus especially among younger patients. Diagnosis of hypertension requires serious and careful approach. The use of a 24-hour ABPM should be considered and carried out as soon as possible in patients with presence of tinnitus. Despite our results are from the limited number of patients with tinnitus, the diagnostic of arterial hypertension is very important, as several prospective studies have reported that ABPM give better prediction of clinical outcomes compared with conventional clinic or office blood pressure measurements. The inner ear, like the brain, is totally lacking in energy reserves. Its metabolism depends directly on the supply of oxygen and glucose from the blood supply. Alterations in glucose metabolism therefore have great potential for disturbing the workings of the inner ear.

Bratislava is currently experiencing massive development, and its developers are very active. As the city develops, the improvement of its public transport becomes increasingly crucial. Public transport (PT) must be ecological, economical, and accessible to all social groups of the population. Bratislava currently has the opportunity to change the modal split in favor of PT and thus end the decline that began in the early 1990s. Rail transport is an ecological type of PT incorporated into smart cities, contributing to city land use. The current PT rail track in Bratislava comprises tram and train infrastructure. Trains ensure the transportation of people from the municipalities surrounding Bratislava, while trams ensure the transportation of people within the city. Tram and train PT must be merged, as their integration could improve traveling times. Bratislava is suitable for the creation of a dual rail transport system covering the urbanized area. The goal of this article is to present a technical solution for a double-gauge system for operation, considering traffic engineering and planning to aid decision making. Considerable professional and expert work was undertaken, in contrast to the political administration’s “decision making”. Cases from Central Europe are presented.

s From The 19Th Colloquium Of The International Society Of Dermatopathology (Isd), November 5-7, 1998, Madrid, Spain