Routine Clinical Practice In Germany Research Articles

Effectiveness and safety of bempedoic acid in routine clinical practice: 1-year follow-up snapshot of the MILOS German cohort

Abstract Background Low-density lipoprotein cholesterol (LDL-C) has an established role in the development of atherosclerotic cardiovascular disease. The 2019 ESC/EAS dyslipidaemia guidelines recommended more intensive treatment goals, however, many patients do not reach them. Bempedoic acid (BA) is a first-in-class ATP citrate lyase inhibitor that lowers LDL-C levels. There is limited data on the use of BA and BA + ezetimibe (EZE) fixed-dose combination (FDC) in clinical practice. Purpose The purpose of this snapshot of 1-year follow-up data from the MILOS study is to evaluate the effectiveness and safety of BA and its FDC in routine clinical practice in Germany. Methods MILOS is a European, prospective, observational, non-interventional study in adult patients with primary hypercholesterolaemia or mixed dyslipidaemia. Patients were recruited from 126 sites in Germany between January 2021 and January 2022, and are followed up for 1–2 years after baseline measurements. Here, we summarise 1-year follow-up data from a snapshot taken on January 13th, 2023. Results Of 992 patients enrolled in Germany, 714 had either completed their 1-year follow-up or discontinued the study prematurely, and 524 of these 714 patients attended their 1-year follow-up visit. For this snapshot, 714 patients are used when determining cardiovascular (CV) outcomes and safety endpoints, and 524 patients are used when reporting efficacy data. The overall mean (SD) age of the population (n=524) was 64.7 (10.0) years, and 60.7% were male. Patients treated with BA/BA+EZE FDC had an overall mean LDL-C level of 2.18 mmol/L (84.1 mg/dL) at 1 year compared with 3.20 mmol/L (123.6 mg/dL) pre-treatment, representing a mean relative LDL-C reduction of 27.3%. Overall, 25.8% (135/524) of patients had reached their LDL-C goal after 1 year of treatment compared with 4.0% (21/524) pre-treatment (Figure 1A and 1B). The overall incidence rate of the composite endpoint of major adverse cardiovascular event (4-component MACE) including CV death, non-fatal myocardial infarction, non-fatal stroke, and coronary revascularisation (n=714) was 3.36%. At 1-year follow-up, 19% (136/714) of patients had an adverse drug reaction (ADR) suspected to be related to BA/BA+EZE FDC, and 0.8% (6/714) had serious ADRs, as deemed by the investigator. Conclusion This snapshot analysis of 1-year follow-up data suggests that the addition of BA to other lipid-lowering therapies increases the proportion of patients at LDL-C goal by ∼6-fold in the observed cohort. The safety and tolerability profile of bempedoic acid are in line with data from randomised controlled trials.

Edoxaban in patients with non-valvular atrial fibrillation after percutaneous coronary intervention: ENCOURAGE-AF design

Approximately one fifth of patients diagnosed with atrial fibrillation (AF) undergo a percutaneous coronary intervention (PCI). Current guidelines recommend different combinations and durations of triple or dual antithrombotic therapy for these patients but data on the implementation of these recommendations in clinical routine are scarce. ENCOURAGE-AF is a prospective, non-interventional, non-comparative, multicentre study. Approximately 720 patients will be consecutively enrolled from 70 participating sites across Germany. Patients with non-valvular AF treated with edoxaban, who have undergone successful PCI, have no planned elective cardiac intervention during the study period, have capability, availability, and willingness for follow-up by telephone interview during the study, are aged ≥ 18 years with life expectancy ≥ 1 year, and provide written informed consent, will be included. Eligible patients will be enrolled between 4- and 72-h after completing a successful PCI. Duration of exposure to and dosing regimens of edoxaban, antiplatelet agents and other concomitant medications of interest will be monitored in line with the clinical practice. Physician- and patient-reported clinical events, adverse drug reactions, patient quality of life (EQ-5D-5L) and health resource utilisation (HRU) parameters will be evaluated at 30 days and 1-year post-PCI. The ENCOURAGE-AF non-interventional study will provide insights into the patterns of edoxaban usage in combination with antiplatelet treatment and other concomitant medications in AF patients with a successful PCI over a 1-year time period during routine clinical practice in Germany. The effectiveness and safety of edoxaban in this patient population, as well as patients’ quality of life and HRU will be evaluated.Trial registration: Clinicaltrial.gov NCT04519944, registered on 20 August 2020.

Subcutaneous abatacept for the treatment of rheumatoid arthritis in routine clinical practice in Germany, Austria, and Switzerland: 2-year retention and efficacy by treatment line and serostatus.

The ASCORE study on treatment for rheumatoid arthritis (RA) showed better retention and clinical response rates for abatacept as first-line versus later-line therapy. This post hoc analysis of ASCORE assessed 2-year retention, efficacy, and safety of subcutaneous (SC) abatacept in Germany, Austria, and Switzerland. Adults with RA who initiated SC abatacept 125mg once weekly were assessed. Primary endpoint was abatacept retention rate at 2years. Secondary endpoints: proportions of patients with low disease activity (LDA)/remission per Disease Activity Score in 28 joints based on erythrocyte sedimentation rate (≤ 3.2), Simplified Disease Activity Index (≤ 11), and Clinical Disease Activity Index (≤ 10). Outcomes were analyzed by treatment line and serostatus. For the pooled cohort, the 2-year abatacept retention rate was 47.6%; retention was highest in biologic-naïve patients (50.5% [95% confidence interval 44.9, 55.9]). Patients seropositive for both anti-citrullinated protein antibody (ACPA) and rheumatoid factor (RF; + / +) at baseline had a higher 2-year abatacept retention rate than patients with single seropositivity for either APCA or RF or double-seronegativity (- / -), irrespective of treatment line. At 2years, a higher proportion of patients who were biologic-naïve were in LDA/remission than patients with one or ≥ two prior biologics. A higher proportion of patients with + / + RA (compared with - / - RA) had abatacept retention after 2years. Early identification of patients with seropositive RA may facilitate a precision-medicine approach to RA treatment, leading to a higher proportion of patients in LDA/remission. NCT02090556; date registered: March 18, 2014 (retrospectively registered). Key Points • This post hoc analysis of a German-speaking subset of European patients with RA from the global ASCORE study (NCT02090556) showed that retention of SC abatacept within this subset was 47.6%, with good clinical outcomes after 2 years. • Patients with double-seropositive RA (ACPA and RF positive) had higher retention of abatacept than patients with double-seronegative RA (ACPA and RF negative). Retention and clinical responses were highest for patients who were biologic-naïve compared with patients who had one or ≥ two prior biologic treatments. • These real-world data may be useful for clinicians in informing individualized treatment pathways for patients with RA, and fostering superior disease control and clinical outcomes.

First-line nab-paclitaxel plus carboplatin for patients with advanced non-small cell lung cancer: Final results of the NEPTUN study.

Real-world data on the first-line treatment of patients with advanced non-small cell lung cancer (NSCLC) are still limited. The NEPTUN study evaluated effectiveness and safety of first-line nab-paclitaxel (Abraxane) plus carboplatin (nab-P/C) in patients with advanced NSCLC in routine clinical practice in Germany. Patients included in our study were aged ≥18 years, diagnosed with locally advanced or metastatic NSCLC and with decision for first-line nab-P/C in routine clinical practice. Primary objective was 6-month progression-free survival rate (PFS6), secondary objectives included overall survival (OS), overall response rate (ORR) and safety. From 2016 to 2019, 408 patients from 75 sites were enrolled. PFS6 was 39.5% (95% CI: 34.2-44.8), median PFS was 5.1months (95% CI: 4.6-5.6), ORR was 42.9% (95% CI: 37.7-48.2). Median OS was 10.5months (95% CI: 9.2-11.6). In subgroup analyses, median OS for squamous vs non-squamous histology was 11.5months (95% CI: 9.2-13.8) vs 9.8months (95% CI: 8.1-11.3) and for patients aged ≥70 vs <70 years median OS was 12.4months (95% CI: 9.8-15.1) vs 9.6months (95% CI: 7.7-11.1). Adverse events (AEs) related to nab-paclitaxel were reported in 247 (66.4%) patients, while carboplatin-related AEs were documented in 224 (60.2%) patients. Most frequently related AEs were leukopenia (22.3%) for nab-paclitaxel and anemia (20.2%) for carboplatin. Nab-P/C-related deaths were reported in 2 (0.5%) patients (sepsis and neutropenic sepsis). No new or unexpected safety signals emerged. These results support the effectiveness and safety of first-line nab-P/C in patients with advanced NSCLC reported in the pivotal trial and highlight the clinical value of this regimen in the real-world setting.

Association between COVID-19 and subsequent vascular events in primary care patients in Germany

ObjectivesThe aim of this study was to investigate the relationship between COVID-19 diagnosis and the risk of developing a first-ever vascular event (VE) compared with the same risk in those with respiratory tract infection (RTI). Study designThis was a retrospective cohort study. MethodsThis study using data from Disease Analyzer Database (IQVIA) included patients aged ≥18 years with at least one visit to a German practice during the index period. VEs were defined as cardiovascular or cerebrovascular events. Two cohorts were created: patients with a diagnosis of COVID-19 and those diagnosed with RTI. These were matched using propensity scores. Kaplan–Meier curves were created for the purposes of time to event analysis. A Poisson model was used to calculate incidence rates and derive incidence rate ratios (IRRs). ResultsA total of 58,904 patients were matched. There was no significant association between COVID-19 diagnosis and increased incidence of VE events among females (IRR [95% confidence interval (CI)]: 0.96 [0.82–1.11] and 1.30 [0.88–1.81]) or males (IRR, 95% CI: 0.91 [0.78–1.05] and 1.13 [0.80–1.62]). Overall, no significant association between COVID-19 diagnosis and incidence of VE was observed across age categories except for cardiovascular vascular events in the age category ≥70 years (IRR [95% CI]: 0.78 [0.67–0.94]). ConclusionsOverall, our study suggests that COVID-19 diagnosis was not associated with an increased risk of developing VE compared with RTI diagnosis. However, further research in a variety of healthcare settings and regions is needed to confirm these preliminary findings from our cohort, which is a good reflection of routine clinical practice in Germany.

Medication adherence with denosumab in patients with bone metastases from solid tumors treated in routine clinical settings: a retrospective study

PurposeTo describe (non)adherence with denosumab among patients with solid tumors and bone metastases.MethodsThis retrospective, observational study pooled data from two completed prospective, multicenter cohort studies (X-TREME; Study 240) in adult patients with bone metastases from primary breast, prostate, lung, kidney, or other solid cancer types and administered denosumab 120 mg in routine clinical practice in Germany and Central and Eastern Europe. The studies were conducted between May 2012 and May 2017; pooled analysis was completed in August 2021. Medication adherence was described according to a three-component consensus taxonomy: initiation (first-ever administration ≤ 90 days from bone metastasis diagnosis), implementation (actual vs prescribed dosing; optimal implementation = regular/consistent dosing), and persistence (≤ 60-day gap between administrations at 3, 6, 9, and 12 months). Descriptive analyses were conducted for each cancer type.ResultsThe analysis included 1748 patients with solid tumors and bone metastases. Adherence with denosumab was generally high across the initiation, implementation, and persistence phases. Most patients experienced timely initiation (from 64.4% [kidney cancer] to 81.2% [breast cancer]) and optimal implementation (from 62.4% [lung cancer] to 72.5% [breast cancer]). The proportion of patients who were persistent with treatment at 6 months ranged from 41.4% (lung cancer) to 77.8% (prostate cancer).ConclusionsThis study revealed variations by cancer type in the initiation, implementation, and persistence of denosumab in patients with solid tumors and bone metastases in routine clinical practice. Further cancer-specific studies are warranted to examine the determinants of (non)adherence with denosumab, and potential ways to improve medication adherence.

Results of a Prospective Non-Interventional Post-Authorization Safety Study of Idelalisib in Germany

BackgroundIn pivotal studies, idelalisib demonstrated remarkable efficacy and manageable tolerability in patients with chronic lymphocytic leukemia (CLL) and follicular lymphoma (FL). This prospective, multicenter, non-interventional post-authorization study assessed the characteristics, clinical management, and outcome of CLL and FL patients receiving idelalisib in routine clinical practice in Germany. PatientsObservational study in CLL and FL patients treated with idelalisib between September 2015 and December 2020. ResultsA total of 147 patients with CLL and FL were included with a median age of 75 and 71 years, respectively. More than 80% of patients presented with comorbidity and many CLL patients with documented high-risk genetic features, including del(17p)/TP53 mutation or unmutated IGHV. The median progression-free survival (PFS) and overall survival (OS) were not reached in the CLL cohort irrespective of del(17p)/TP53 or unmutated IGHV. The estimated 6-month PFS and OS rates in CLL were 82% and 92%. The estimated 6-month PFS and OS rates for FL were 32.2% and 77.2%. Overall response rates in the CLL and FL cohorts were 70.4% and 36.4%, with the presence of high-risk genetics having no negative impact. No unexpected adverse events were observed. Most frequently reported adverse drug reactions (ADRs) were diarrhea, nausea, pneumonia, rash, and fatigue. ConclusionThis real-world study shows that idelalisib is an effective therapy for CLL and FL, regardless of age and high-risk genetic features, consistent with results from previous clinical trials. Collected safety data and the pattern of ADRs reflect those from previous studies.

Management of Patients with Relapsed and/or Refractory Multiple Myeloma Treated with Novel Combination Therapies in Routine Clinical Practice in Germany.

IntroductionMultiple myeloma remains an incurable plasma cell malignancy which, despite improvements in overall survival over the last decade, is characterized by recurrent relapse and is associated with a poor prognosis. This study investigates the use of novel agents in current real-world clinical practice in the management of relapsed and/or refractory multiple myeloma (RRMM) in Germany over different lines of therapy.MethodsA retrospective chart review was conducted for patients with RRMM treated at multiple centers across Germany between May 2017 and June 2018. Variables included patient demographics and clinical characteristics, current and prior treatment regimens, treatment response, cytogenetic abnormalities, testing methodology, and resource utilization.ResultsData were analyzed from 484 patients from 47 centers across Germany (60% male; average age over 70 years; majority at International Staging System stage 2 or 3). Bone pain and anemia were the most common symptoms at diagnosis, with 63% of patients receiving osteoprotective drugs. Approximately one-third (32%) of patients had received autologous stem cell transplantation and approximately 70% underwent cytogenetic testing. After failure to respond to first-line treatment, most patients received regimens containing second-generation proteasome inhibitors and monoclonal antibodies, with overall response rates greater than 90% in second line (95% and 90% for daratumumab-based and carfilzomib-based therapies, respectively). The incidence of unplanned hospitalization ranged from 11% to 16% across all treatment lines, with longer hospital stays required for treatment administration than for treatment-related toxicity.ConclusionAlthough treatment patterns for RRMM in Germany differ by line of therapy and are adapted as disease progresses, patients mostly receive combination regimens with carfilzomib or daratumumab in second and third lines, with high overall response rates achieved in all lines.Supplementary InformationThe online version contains supplementary material available at 10.1007/s12325-021-02022-z.

Long-term real-world effectiveness and safety of fingolimod over 5 years in Germany

ObjectiveTo evaluate the 5-year real-world benefit–risk profile of fingolimod in patients with relapsing–remitting MS (RRMS) in Germany.MethodsPost-Authorization Non-interventional German sAfety study of GilEnyA (PANGAEA) is a non-interventional real-world study to prospectively assess the effectiveness and safety of fingolimod in routine clinical practice in Germany. The follow-up period comprised 5 years. Patients were included if they had been diagnosed with RRMS and had been prescribed fingolimod as part of clinical routine. There were no exclusion criteria except the contraindications for fingolimod as defined in the European label. The effectiveness and safety analysis set comprised 4032 and 4067 RRMS patients, respectively.ResultsAt the time of the 5-year follow-up of PANGAEA, 66.57% of patients still continued fingolimod therapy. Annualized relapse rates decreased from baseline 1.5 ± 1.15 to 0.42 ± 0.734 at year 1 and 0.21 ± 0.483 at year 5, and the disability status remained stable, as demonstrated by the Expanded Disability Status Scale mean change from baseline (0.1 ± 2.51), the decrease of the Multiple Sclerosis Severity Score from 5.1 ± 2.59 at baseline to 3.9 ± 2.31 at the 60-months follow-up, and the percentage of patients with ‘no change’ in the Clinical Global Impression scale at the 60-months follow-up (78.11%). Adverse events (AE) occurring in 75.04% of patients were in line with the known safety profile of fingolimod and were mostly non-serious AE (33.62%) and non-serious adverse drug reactions (50.59%; serious AE 4.98%; serious ADR 10.82%).ConclusionsPANGAEA demonstrated the sustained beneficial effectiveness and safety of fingolimod in the long-term real-world treatment of patients with RRMS.

POSA399 Treatment Pattern, Mortality and Costs Among BCG-Treated Non-Muscle Invasive Bladder Cancer (NMIBC) Patients in Germany

Intravesical Bacillus Calmette-Guerin (BCG) is the first line treatment for patients with high-risk NMIBC. There is a lack of contemporary data on its utilisation in routine clinical practice in Germany. This study aimed to describe the treatment patterns of adult patients treated with BCG as well as their health resource utilisation, cost burden and mortality rate.

Renal Function and Patient-Reported Outcomes in Stable Kidney Transplant Patients Following Conversion From Twice-Daily Immediate-Release Tacrolimus to Once-Daily Prolonged-Release Tacrolimus: A 12-Month Observational Study in Routine Clinical Practice in Germany (ADAGIO)

IntroductionThis 12-month, noninterventional study on routine clinical practice in Germany evaluated renal function in stable kidney transplant recipients converted from immediate-release tacrolimus (IR-T) to prolonged-release tacrolimus (PR-T). MethodsRenal function was assessed in 183 patients by estimated glomerular filtration rate using the modification of diet in renal disease-4 formula. Self-reported gastrointestinal health-related quality of life, adherence, satisfaction with PR-T, suspected rejection episodes, and safety were also assessed at conversion and at 3, 6, and 12 months. ResultsConversion from IR-T to PR-T resulted in stable kidney function over 12 months, with a difference in estimated glomerular filtration rate between the first and final visits of 0.1 mL/min/1.73 m2 (95% confidence interval, −1.6, 1.8). Eight patients experienced an acute rejection episode (4.4%). At each assessment, gastrointestinal health-related quality of life was low and adherence was high. Most patients reported that they were very satisfied (69.8%) or satisfied (28.1%) with PR-T at the final visit. Among patients reporting a preference, 78.4% preferred PR-T, 2.2% preferred IR-T, and 19.4% reported no preference. The safety profile of PR-T was consistent with that previously described. ConclusionConversion of stable kidney transplant recipients from IR-T to PR-T provided stable kidney and graft function over 12 months (Verband Forschender Arzneimittelhersteller--registered study: NIS ADV-02).

PERSEUS 24-month analysis: a prospective non-interventional study to assess the effectiveness of intravitreal aflibercept in routine clinical practice in Germany in patients with neovascular age-related macular degeneration

PurposeTo evaluate the real-world effectiveness of intravitreal aflibercept injections in Germany in patients with neovascular age-related macular degeneration over 24 months.MethodsPERSEUS was a prospective, non-interventional cohort study. The primary endpoint was the mean change in visual acuity (VA) from baseline. Secondary endpoints included the proportion of patients with a VA gain or loss of ≥ 15 letters and the frequency of injections and examinations. Patients with regular (bimonthly after 3 monthly injections during year 1 and ≥ 4 injections in year 2) and irregular (any other) treatment were analyzed. The last observation carried forward (LOCF) and the observed cases (OC) approach was applied for primary endpoint analysis to account for missing data.Results803 patients were considered for effectivity analysis. At month 24, only 38% of the patients were still under observation. The LOCF population included 727, the OC population 279 patients. Treatment-naïve patients improved by 6.3 (LOCF)/8.1 (OC) letters with regular treatment over 24 months but only by 3.3 (LOCF)/3.1 (OC) letters with irregular treatment. The proportion of treatment-naïve patients achieving a VA improvement of ≥ 15 letters was similar between regularly and irregularly treated cohorts. However, considerably more patients in the irregular cohorts experienced a VA worsening of ≥ 15 letters than in the regular cohorts (LOCF: 18.7% vs. 7.4%).ConclusionsRegular IVT-AFL treatment resulted in better VA outcomes than irregular treatment at month 24. However, only a minority of patients received regular treatment over a 2-year period.

Multicenter, Observational Study of Lanreotide Autogel for the Treatment of Patients with Acromegaly in Routine Clinical Practice in Germany, Austria and Switzerland.

Evidence from controlled trials has shown that lanreotide autogel is effective in achieving biochemical and symptom control in patients with acromegaly. However, it is important to better understand the real-world patient population receiving lanreotide autogel treatment. In this non-interventional study the long-term treatment response to lanreotide autogel in adult patients with acromegaly from office-based centers or clinics in Germany, Austria and Switzerland was studied. Assessments included growth hormone and insulin-like growth factor-I levels, symptoms, quality of life, lanreotide plasma levels and tumor somatostatin receptor subtype expression. The primary endpoint was achievement of full biochemical control, defined as growth hormone ≤2.5 µg/L and insulin-like growth factor I normalization at month 12. 76 patients were enrolled from 21 sites. 7/51 (13.7%) patients of the efficacy population had full biochemical control at baseline, 15/33 (45.5%) at month 12 and 10/26 (38.5%) at month 24 of treatment. At 12 months of treatment higher rates of biochemical control were observed in the following subgroups: older patients (>53 years [median]), females, treatment-naïve patients, and patients with a time since diagnosis of longer than 1.4 years (median). No clinically relevant differences in acromegaly symptoms or quality of life scores were observed. Median fasting blood glucose and glycated hemoglobin levels remained unchanged throughout the study. No new safety signals were observed. Overall tolerability of treatment with lanreotide autogel was judged by 80.8% of the enrolled patients at month 12 as 'very good' or 'good'. Treatment with lanreotide autogel in a real-world setting showed long-term effectiveness and good tolerability in patients with acromegaly.

Management of Patients with Relapsed/Refractory Multiple Myeloma (RRMM) Treated with Novel Therapies in Routine Clinical Practice in Germany

Management of Patients with Relapsed/Refractory Multiple Myeloma (RRMM) Treated with Novel Therapies in Routine Clinical Practice in Germany

Estimating the Epidemiological and Economic Impact of Implementing Preoperative Anaemia Measures in the German Healthcare System: The Health Economic Footprint of Patient Blood Management.

IntroductionThis study aimed to quantify the potential epidemiological and health economic benefits of implementing preoperative anaemia measures (PAMs) in clinical practice in the German healthcare system.MethodsAn evidence-based health economic model was developed to assess the possible impact of implementing PAMs, the first pillar of patient blood management (PBM), in a German population. The analysis of two risk factors—iron-deficiency anaemia (IDA) and receipt of a red blood cell concentrate (RBC) transfusion during elective surgery—allowed the estimation of relative risks (RRs), average cost per patient, average length of hospital stay, and avoided hospital deaths after the implementation of PAMs.ResultsA total of 4,591,060 patients who had undergone elective surgery during 2015 were identified, of which 29,170 (0.64%) were diagnosed with preoperative IDA. These patients had an increased RR of receiving a RBC transfusion during surgery (RR 5.031; 95% confidence interval [CI] 4.928, 5.136) and increased mortality risk (RR 3.630; 95% CI 3.401, 3.874) versus patients without IDA. Patients who received a RBC transfusion during surgery had a 24.6-times higher risk of death than those who did not (RR 24.593; 95% CI 24.121, 25.075). Average cost of treatment was €7883 in patients with IDA, €21,744 in patients with IDA and RBC transfusion, and €4560 in patients without risk factors. The model identified 29,714 patients (0.65%) who had received a RBC transfusion and who potentially had IDA but remained undiagnosed before surgery. Hypothetical implementation of PAMs would have resulted in an estimated annual net hospital direct cost saving of €1029 million (1.58%) of total hospital direct costs of the German healthcare system and 3036 hospital deaths (0.07%) avoided.ConclusionsThis model estimated the impact of implementing PAMs for patients with IDA undergoing elective surgery. A significant number of deaths, costly treatments, and hospital days could have been avoided by the introduction of PAMs in routine clinical practice in Germany.

Distribution of the 21-Gene Breast Recurrence Score in Patients with Primary Breast Cancer in Germany.

Background Multigene assays are being used increasingly to aid in decision-making about chemotherapy in breast cancer. Here, we present the 21-gene recurrence score (RS) of patients tested in routine clinical practice in Germany. Patients and Methods In a retrospective analysis, 4695 patients with hormone receptor-positive and HER2-negative early breast cancer (pT1 – 3, pN0 – 1, M0) were included in whom RS testing was conducted in Germany between November 2015 and July 2018. RS groups as defined in the TAILORx trial (RS result 0 – 10; 11 – 25; 26 – 100) were used. Results Of these patients, 21% were assigned to the low RS group, 63% to the midrange RS group, and 15% to the high RS group. 1772 (81%) of 2175 node-negative patients over 50 years of age were grouped either into the low RS group or the midrange RS group. The portion of patients with a low or midrange RS was 90% among node-positive patients (1284 of 1432 patients), 79% among patients with Ki-67-high (≥ 20%) tumors (1829 of 2310 patients), 86% vs. 70% among patients with G2 and G3 tumors (3244 of 3762 patients and 368 of 522 patients), respectively, 88% among patients with a tumor size of > 5 cm (140 of 159 patients), and 82% among node-negative patients at high clinical risk (1110 of 1352). Conclusions The distribution of the 21-gene RS in German patients that were tested in routine clinical practice indicates that, according to the results of the TAILORx trial, chemotherapy may not be beneficial in most of these.

PS1407 TWICE WEEKLY CARFILZOMIB IS AN ACCEPTED TREATMENT BY PATIENTS WITH MULTIPLE MYELOMA WHO HAVE RECEIVED AT LEAST ONE PRIOR THERAPY: INTERIM RESULTS OF THE CARO STUDY

Background:Carfilzomib (Kyprolis®) has shown an improved overall survival and a good tolerability in two phase 3 studies (ENDEAVOR, ASPIRE) in patients (pts) with relapsed or refractory multiple myeloma and, thus, received market approval in the combination regimens carfilzomib/lenalidomide/dexamethasone (CAR/LEN/DEX) and carfilzomib/dexamethasone (CAR/DEX). CAR is intended to be given twice weekly in both regimens. In daily practice, poor adherence and persistence to anticancer treatment are serious issues as nonadherence has been shown to lead to higher treatment failure rates, worse outcome and higher total costs of care.Aims:The key objective of the CARO study is to collect real‐world data on the implementation of the recently approved regimens CAR/LEN/DEX and CAR/DEX in routine clinical practice in Germany with a special focus on treatment adherence.Methods:The prospective, multicenter, non‐interventional CARO study was designed to collect data on 300 pts with multiple myeloma from 90 sites across Germany. The primary objective is pts’ adherence to the CAR therapy as prescribed by the treating physician. Secondary objectives are pts’ adherence to LEN and DEX as well as the evaluation of the implementation of the recommended dosing regimens, i.e. a comparison of the actually administered medication versus recommended medication according to current Summary of Product Characteristics (SmPC). Exploratory objectives are effectiveness, safety and health‐related quality of life. The first interim analysis of the CARO study was scheduled 12 months after the recruitment of the first patient.Results:From 10/2016 through 10/2017, 102 pts have been enrolled, thereof 68 pts into the CAR/LEN/DEX cohort and 32 pts into the CAR/DEX cohort. Here, the focus is on the implementation of the recommended dosing regimen in pts who received CAR/LEN/DEX (N = 64). Median age of pts was 72.3 years (range 43.4–84.3), 45.3% were female and 70.3% of pts had a good performance status with a Karnofsky performance score between 80 and 100. The mean relative dose intensity of CAR was 88.1%. 1368 of the scheduled 1591 CAR administrations (86.0%) were given on time. 7.9% (n = 125) of administrations in 43.8% (n = 28) of pts were omitted, 5.0% (n = 80) of administrations in 62.5% (n = 40) of pts were delayed and 1.1% (n = 18) of doses in 18.8% (n = 12) of pts were administered earlier than planned. 1328 of 1466 CAR administrations (90.6%) were given at the recommended dose. 6.2% (n = 91) of doses in 23.4% (n = 15) of pts were reduced, 3.2% (n = 47) of doses in 7.8% (n = 5) of pts were increased. For reasons refer to Figure 1. The mean adherence to the CAR dosing regimen, i.e. the percentage of doses administered as scheduled by the treating physician and not modified for adherence reasons, was 94.8%.Summary/Conclusion:According to our interim results, 86% of CAR administrations were given as scheduled and more than 90% of administrations were given at the recommended dose. Modifications of the recommended CAR regimen were mainly due to safety issues or organizational reasons, but not due to lack of adherence. Though, despite the required twice weekly dosing schedule, the CAR regimen appears to be a well‐accepted treatment by multiple myeloma pts. Results need to be confirmed in the final analysis.image

Management of Patients with Relapsed/Refractory Multiple Myeloma (RRMM) Treated with Proteasome Inhibitor Based Therapy at First Relapse in Routine Clinical Practice in Germany

Background: Proteasome inhibitors (PI) represent an important therapeutic advance in the treatment of patients with relapsed/refractory multiple myeloma (RRMM). In 2017, three distinct PIs (bortezomib [BTZ], carfilzomib [CFZ] and ixazomib [IXA]) were available in Germany but real-world data describing their usage was scarce.Aim: To describe characteristics and treatment experience of PI-treated patients with RRMM in Germany.Methods: A national retrospective medical chart review included consecutive patients treated with at least one dose of PI-based regimen in participating hospitals/centers across Germany between January and June 2017. The following data were extracted until April 2018 or death of patient, whichever occurred first: patient demographics, disease characteristics and treatment history at diagnosis and at initiation of PI-based therapy. Physician assessed treatment response were also collected.Results: Physicians from 44 participating centers extracted 302 patient charts, including 219 patients in 2nd line (2L) and 83 in 3rd line treatment (3L), as shown in Figure 1. Results for 2L patients are described below (Table 1, Figure 2):BTZ-treated patients represented 42% of patients (n=92) with a PI-based therapy in 2L. BTZ was often combined with dexamethasone (dex) alone (77%). Median age was 74 years and 56.5% had an ECOG status ≥2 at 2L initiation. Most patients (86%) did not receive a prior transplant. Median treatment duration was 6 months among 40 patients who completed 2L; based on 38 narratives, 2L was ended as planned (47.4%). Where response was available (n=83), 25% of patients achieved a complete response/very good partial response [CR/VGPR]. Median time to next treatment (TTnT) was 7.5 months for 12 patients who moved to 3L. Patient profiles differed in terms of prior treatment exposure: 22% of patients had been treated with a BTZ-based therapy in both 1L and 2L and 62% switched therapies from 1L lenalidomide (len) to BTZ. None of the patients receiving len in 1L were transplanted. A CR/VGPR was achieved by 65% of prior BTZ-treated patients (13/20) and 30% of patients with prior len therapy (17/57).CFZ-treated patients: 48% (n=106) of patients received CFZ-based therapy in 2L. Of those, 56% (n=59) received CFZ in combination with len/dex (KRd) and 44% (n=47) with dex alone (Kd). Median age was 68 years, 60.4% had an ECOG status of 0-1 at 2L initiation and 49% had received a transplant. In 1L, 82% had received a BTZ-based regimen. Where response was mentioned (n=89), a CR/VGPR was reached in 53% of CFZ-treated patients. Median treatment duration was 6.5 months (24/106). Based on 21 narratives, the main reason for discontinuing CFZ in 2L was disease progression (47.6%). Median TTnT was 9.5 months for 10 patients who moved to 3L. The patient profiles by KRd or Kd combination were as follows: at KRd initiation, median age was 65 years, 10.2% of patients had an ECOG status ≥2 and 72.9% were transplanted. At Kd initiation, median age was 71 years, 76.6% of patients had an ECOG ≥2 and 19.1% were transplanted.IXA-treated patients (n=21) represented only 10% of PI-treated patients in 2L. Median age was 66 years, 71.4% had an ECOG status of 0-1 at 2L initiation, 33% were transplanted, and 72% had received a BTZ combination in 1L. Information on response was premature as it was only available for 13 patients with no CR reached (VGPR 77%). Median treatment duration was 4 months (n=9) and median TTnT was 10 months for 4 patients who moved into 3L.Limitation: The main limitation of the study was the sample size of IXA-treated patients due to open inclusion criteria to select patient charts. This analysis was not powered to compare between PIs. Hence, results are descriptive of the clinical experience with PI-based therapy to date and reflect current treatment practices in Germany in 2017.Conclusion: In Germany, distinct patient characteristics are observed in clinical practice by selected PI-based therapy. Patients treated with novel PI agents in 2L are generally younger and more transplanted than bortezomib-treated patients; these appear to be important considerations when tailoring therapy in RRMM. In addition, the choice between triplet or doublet therapy for CFZ-based combinations seems to reflect prior transplant status and patients' overall functional performance. Evidence suggests that use of novel PI agents such as CFZ can translate into deeper response in 2L. [Display omitted] DisclosuresSteinmetz:Amgen, Celgene, Novartis, Vifor: Research Funding; Amgen; BMS, Celgene, Hexal-Sandoz, Medice, Novartis; Janssen-Cilag; Pharmacosmos; Pfizer, Vifor; Ariad: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Alexion, Amgen, Bayer, Celgene, Janssen-Cilag, Novartis: Other: Travel grants. Singh:Amgen: Employment, Equity Ownership. Lebioda:Amgen: Employment, Equity Ownership. Mantonnier:Kantar Health: Employment, Other: Received funding to conduct this research. Fink:Kantar Health: Employment, Other: Received funding to conduct this research. Rieth:Amgen: Employment, Equity Ownership. Suzan:Amgen: Employment, Equity Ownership. Gonzalez-McQuire:Amgen: Employment, Equity Ownership.

Efficacy and Tolerability of Leuprorelin Acetate (Eligard®) in Daily Practice in Germany: Pooled Data from 2 Prospective, Non-Interventional Studies with 3- or 6-Month Depot Formulations in Patients with Advanced Prostate Cancer

Introduction: We evaluated the efficacy and tolerability of 3- and 6-month leuprorelin acetate (LA) depot formulations (Eligard®, Astellas Pharma GmbH) in patients with advanced prostate cancer treated in routine clinical practice in Germany. Materials and Methods: Data was pooled from 2 prospective, open-label, non-interventional studies in which 1,906 patients were treated for 12 months with either the 3-month (n = 633) or 6-month (n = 1,273) LA formulation. Results: Median prostate-specific antigen levels in the pooled patient population declined from 12.0 ng/mL at baseline to 0.5 ng/mL after 12 months. Prostate-specific antigen reduction was achieved in treatment-naïve and pre-treated patients. Adverse events were documented in 8.8% of patients. Conclusions: These pooled data from routine clinical practice in Germany indicate that LA 3- and 6-month depot injections can effectively reduce prostate-specific antigen levels in a broad patient population with advanced prostate cancer.

Aflibercept for Patients with Neovascular Age-Related Macular Degeneration in Routine Clinical Practice in Germany: Twelve-Month Outcomes of PERSEUS

To explore real-world effectiveness of intravitreal aflibercept injection (IAI) for neovascular age-related macular degeneration (nAMD) in Germany. A 24-month, prospective, noninterventional, noncontrolled, multicenter observational cohort study. Patients (n= 848) with nAMD treated with IAI. Patients (n= 988) were screened at 67 study sites. Therapeutic decisions were made by the treating physician. Primary end point analysis was performed after 12 months for the entire study cohort and for predetermined subgroups of treatment-naïve and previously treated patients. Additionally, outcomes with regular injection intervals (bimonthly after 3 monthly injections) were compared with those of patients with irregularities in their treatment regimen. The primary end point was the mean change in visual acuity (VA) from baseline after 12 months. Other key end points included the proportions of patients gaining 15 letters or more and patients with reading vision (≥70 letters). Furthermore, the number of injections, anatomic measurements, and safety data were recorded. Mean ± standard deviation VA improvement was 5.3±17.4 letters in treatment-naïve patients and-0.1±15.6 letters in previously treated patients (P ≤ 0.0001), and that of the total study group was 2.9±16.8 letters. Baseline VA was 53.4±17.9 letters for treatment-naïve patients, 52.9±18.4 letters for previously treated patients, and 53.2±18.1 letters for the total patient population. Treatment pattern was associated with VA outcome: best outcomes-an average VA gain of 8.0±17.7 letters-were seen in treatment-naïve patients in the regularly treated population, whereas irregularly treated, treatment-naïve patients achieved a mean VA gain of only 4.0±17.1 letters. Among previously treated patients, regular treatment also was associated with better outcomes (+3.1±10.7 vs.-1.1±16.8 letters). For the total study group, the mean VA gain was the following: regularly treated population, 6.1±15.6 letters; irregularly treated population, 1.5±17.1 letters (P= 0.008). No cases of endophthalmitis were observed during the first 12 months of the study. Adverse events were in line with the known safety profile of IAI. After 12 months of treatment with IAI, treatment-naïve patients showed substantial functional benefit, whereas previously treated patients maintained their VA. With regular IAI treatment, it seems that similar results as those in pivotal IAI studies can be achieved in routine clinical practice.