Objective: The aim of the study was to evaluate the efficacy, tolerability, and safety of once-a day trazodone tablets (Trittico Prolong® 300 mg) in patients with moderate to severe depression in routine clinical practice. Methods: Men and women ≥18 years old with Montgomery-Åsberg Depression Rating Scale (MADRS) scores > 21 and Clinical Global Impression – Severity (CGI/S) ≥4 were included in this post-authorization, non-interventional, observational prospective safety study, conducted in 8 psychiatric centers in the Czech ­Republic. The acute treatment phase lasted 5 weeks: 1 week of titration and 4 weeks of full-dose treatment. Patients had follow-up visits 9 and 21 weeks after commencing ­treatment. Results: Overall, 85 patients were enrolled in the study, of which 80 completed the acute treatment of 5 weeks. There were significant decreases in the overall MADRS score from the baseline mean value of 27.4–21.2 at week 1 (p < 0.001), and a further decrease to 7.9 at week 5 (p < 0.001). The severity of depression according to CGI/S gradually declined. Most patients reported improvement after 6 days of trazodone treatment. The most frequent adverse drug reactions (ADRs) reported were somnolence and fatigue. Conclusions: Trazodone, in the new extended-release formulation, had very good effects in clinical practice, both in previously untreated depressive episodes and in episodes not responsive to previous antidepressive therapy.

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Based on this pilot study, erdosteine seems effective in the treatment of CRSwNP and might become a reasonable alternative to currently used medication. The therapeutical role of erdosteine needs to be further assessed.

12083 Background: Evidence-based antiemetic guidelines offer predominantly consistent recommendations for CINV prophylaxis. However, studies and surveys suggest that adherence to these recommendations is suboptimal. We explored potential inconsistencies between clinical practice and guideline-recommended treatment with a registry evaluating the effect of guideline-consistent CINV prophylaxis (GCCP) on patient outcomes. Methods: This was a prospective, non-interventional, observational, multicenter study designed to assess overall (0-120 h) complete response (CR: no emesis/no rescue use) rates in patients who received GCCP or guideline inconsistent CINV prophylaxis (GICP) using diaries for 5 days following chemotherapy. Cycle 1 results are presented in patients who received either 1) anthracycline/cyclosphosphamide (AC) highly emetogenic chemotherapy (HEC), non-AC HEC or carboplatin, with GCCP for all these groups consisting of prophylaxis with an NK1 receptor antagonist (RA), 5-HT3RA, and dexamethasone (DEX) prior to chemotherapy or 2) moderately emetogenic chemotherapy (MEC), with GCCP consisting of a 5-HT3RA and DEX prior to chemotherapy as per MASCC 2016 guidelines. CR rates for cohorts deemed to be GCCP and GICP were compared using a chi-square test. Results: A total of 1,089 patients were part of the cycle 1 efficacy evaluation. Overall GCCP was 23% for all patients. CR rates were significantly higher in patients receiving GCCP versus GICP (Table). Conclusions: Consistent with prior studies, GCCP was very low. The primary endpoint of the study was achieved as there was a significant benefit of almost 10% improved prevention of CINV when administering GCCP. As per MASCC/ESMO guidelines such an absolute difference should be practice changing. Comprehensive multifaceted strategies are needed to achieve better adherence to antiemetic guidelines. [Table: see text]

Patients with newly diagnosed chronic myeloid leukemia (CML) frequently receive imatinib. Although initial response rates are high, imatinib fails in up to 40% of patients because of disease resistance, frequently because of BCR-ABL kinase domain mutations, or side effects. Patients who discontinue imatinib may have a response to second-generation tyrosine kinase inhibitors (TKIs). Ponatinib (PON) is a potent oral TKI active against unmutated and mutated BCR-ABL kinase. PON is indicated also in Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) patients. Clinical activity of PON was confirmed in the phase II PACE trial, however lack of real world data is evident. The aim of this non-interventional study was to analyze data on PON treatment and its efficacy in the Czech patients with CML / Ph+ ALL. The study was designed as a one-off retrospective data collection from 3 national registry databases INFINITY, CAMELIA and DATOOL ALL in the period 2014-2018. In total, the study comprised 27 patients treated with PON at 7 centers; 16 (59.3%) patients were treated for chronic phase (CP) CML, 4 (14.8%) patients for accelerated- or blast-phase (AP/BP) CML and 7 (25.9%) patients for Ph+ ALL. The 16 CP CML patients (68.8% males) had median age at the start of PON treatment 59.7 years (range 28.6-81.4), were heavily pretreated (75% with ≥ 3 TKIs) with median time from diagnosis to start of PON treatment 4.8 (0.2-16.8) years; 37.5% of them had mutations (18.8% with T315l), 75.0% had comorbidities. The 11 AP/BP CML / Ph+ ALL patients (54.5% males) were younger with median age 56.6 (31.2-74.7) years, were less pretreated (36.4% with ≥ 3 TKIs) with a shorter time from diagnosis to start of PON treatment 2.0 (0.4-22.0) years; almost twice as many (72.7%) of them had mutations (54.5% with T315l), 63.6% had comorbidities. The most common reason for switching to ponatinib was hematologic resistance (37.5% of CP CML and 54.5% of AP/BP CML / Ph+ ALL patients). The other most frequent indications were cytogenetic resistance, non-hematologic and hematologic intolerance (18.8%, 12.5% and 12.5% of CP CML patients and 9.1%, 9.1% and 0% of AP/BP CML / Ph+ ALL patients, respectively). Interestingly, starting dose of PON was 45 mg/day as recommended in the product SmPC only in of about half of the patients (43.8% of CP CML and 54.5% of AP/BP CML / Ph+ ALL patients). Median treatment duration was 16.1 (0.8-49.9) months in CP CML patients and only 2.9 (0.2-36.1) months in AP/BP CML / Ph+ ALL patients. Early (in the first 3 months) and late termination of the treatment occurred in 12.5% and 31.3% of CP CML and 54.5% and 27.3% of AP/BP CML / Ph+ ALL patients, respectively. Disease progression was the major reason for treatment termination (50%). In terms of safety, only 1 patient discontinued therapy due to congestive heart failure, and 1 due to vascular adverse event although more than half of the patients had cardiovascular comorbidities and history of cardiovascular disease. PON efficacy was evaluated in 14 CP CML patients and 5 AP/BP CML / Ph+ ALL who were treated beyond 3 months (Figure 1). More than half of CP CML patients achieved MMR (57.1%) and 40% of AP/BP CML / Ph+ ALL achieved undetectable disease. Estimated percentage of CHR, CCyR and MMR in CP CML patients after one year of treatment was 85.7%, 50% and 50%, respectively. Nevertheless, 5 (35.7%), 2 (14.3%) and 1 (7.1%) patients had CHR, CCyR and MMR at start of PON treatment, respectively. In AP/BP CML / Ph+ ALL patients, estimated percentage of CR and CMR after one year was 100% and 40%, respectively. However, 2 patients (20%) had CR at the start of PON treatment. Despite limited number of patients, our analysis confirmed PON efficacy in real-life setting with a significant proportion of heavily pre-treated patients achieving durable molecular responses in both CP and AP/BP CML / Ph+ ALL groups. Our data are comparable to the PACE trial results. This study partially fills the gap in RWE data and significantly contributes to the evaluation of real-life clinical practice in rare disease area. Figure 1. Cumulative incidence of responses on ponatinib treatment in A) CP CML (N=14) and B) AP/BP CML / Ph+ ALL (N=5) patients that continued ponatinib treatment beyond 3 months. Figure 1 Disclosures Žáčková: Bristol Myers Squibb: Consultancy; Novartis: Consultancy; Angelini: Consultancy; Incyte: Consultancy. Kellnerová:Angelini Pharma: Employment.