German Non-interventional Study Research Articles

A-200 Mogamulizumab in patients with mycosis fungoides or Sézary syndrome: Update on the German non-interventional MINT study

A-200 Mogamulizumab in patients with mycosis fungoides or Sézary syndrome: Update on the German non-interventional MINT study

873P Nivolumab (NIVO) in the first-line (1L) or second-line (2L) and later (2L+) settings in patients (pts) with recurrent and/or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN): Updated results from the German non-interventional study (NIS), HANNA

873P Nivolumab (NIVO) in the first-line (1L) or second-line (2L) and later (2L+) settings in patients (pts) with recurrent and/or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN): Updated results from the German non-interventional study (NIS), HANNA

1348P First-line (1L) nivolumab (N) + ipilimumab (I) with 2 cycles of platinum-based chemotherapy (C) in patients (pts) with metastatic non-small cell lung cancer (mNSCLC): Results from an interim analysis of the German non-interventional study (NIS) FINN

1348P First-line (1L) nivolumab (N) + ipilimumab (I) with 2 cycles of platinum-based chemotherapy (C) in patients (pts) with metastatic non-small cell lung cancer (mNSCLC): Results from an interim analysis of the German non-interventional study (NIS) FINN

Overall survival in patients with BRCA-mutated platinum-sensitive relapsed ovarian cancer (PSROC) treated with olaparib maintenance: Real-world data of the C-PATROL study.

e17542 Background: Maintenance monotherapy with PARP-inhibitor (PARPi), olaparib has previously shown good effectiveness and tolerability in total population of patients with PSROC who were in response to platinum-based chemotherapy (PBC) in the C-PATROL study. Here we present the overall survival (OS) data in different subgroups. Methods: The prospective German non-interventional study C-PATROL (NCT02503436) captured routine clinical data of olaparib maintenance according to label in patients with BRCA-mutated PSROC treated with PBC. The primary endpoint was PFS, relevant secondary endpoints included OS and safety. Data were analyzed by descriptive statistics. Results: Between 10/2015 and 10/2019, 277 patients were enrolled. The ITT set (study selection criteria fulfilled) comprised 267 patients (median age: 60 yrs; ECOG ≤1: 93%; ≥2 relapses: 32%; ≥3 prior PBC: 29%). Median follow-up was 23.5 months (range 0.0–80.5) and median olaparib treatment duration was 13.6 months (0.1–80.9). 10% of patients received olaparib for ≥ 5 years and 8% of patients received further PARPi also as subsequent treatment. Median OS was 35.4 months (95% CI 29.2–49.9). The longest median OS was observed in patients with a complete debulking after the surgery at current relapse, a complete response (CR) to the current PBC and a BRCA2 mutation. Adverse events (AEs) were consistent with the known tolerability profile of olaparib (safety set: n=274; any AE: 95%, AE of CTCAE grade ≥ 3: 40%, olaparib discontinuation due to AE: 11%; most common AE any CTCAE: nausea (46%), fatigue (39%), anaemia (31%), and vomiting (17%); most common AE CTCAE grade ≥ 3: anaemia (14%)). Conclusions: Olaparib is effective and safe in the real-world setting. In olaparib-treated patients with BRCA-mutated PSROC longer OS was observed mainly with respect to resection status after debulking surgery at current relapse, to tumor burden at the therapy start and BRCA mutation type. Our data underline the role of cytoreduction and platinum response in the context of PARPi maintenance therapy. Clinical trial information: NCT02503436 . [Table: see text]

Etanercept in Axial Spondyloarthritis, Psoriatic Arthritis, and Plaque Psoriasis: Real-World Outcome Data from German Non-interventional Study ADEQUATE.

For chronic diseases such as axial spondyloarthritis (axSpA), psoriatic arthritis (PsA), and plaque psoriasis (PsO), treatment goals include remission or at least low disease activity (LDA) by 12weeks. Improvements in symptoms such as pain and fatigue should also be treatment goals. ADEQUATE was a German, prospective, non-interventional study to evaluate the proportion of patients with rheumatoid arthritis, PsA, axSpA, or PsO who, in routine clinical practice, benefit from the continuation of treatment with etanercept (ETN) beyond 12weeks, even when their treatment goals have not yet been reached. Patient-reported outcomes (PROs) and changes in concomitant glucocorticoid use were also recorded. This article focuses on results for patients with axSpA and PsA; data for patients with PsO are described briefly. In total, 305, 254, and 70 patients with axSpA, PsA, and PsO, respectively, were included. Rates of remission at week12 and week24, respectively, were 19% and 18% for axSpA, 38% and 51% for PsA, and 7% and 19% for PsO. Rates of LDA at week12 and week24, respectively, were 39% and 45% for axSpA, 50% and 60% for PsA, and 34% and 51% for PsO. Extending treatment up to 52weeks was associated with stable rates of or further increases in remission and LDA rates. Improvements in pain, fatigue, and depression (axSpA, PsA, and PsO) and reductions in concomitant glucocorticoid use (axSpA and PsA) were observed. No new safety signals were detected. These findings confirm the effectiveness and safety of ETN in routine clinical practice for several indications and highlight potential benefits of continuing ETN treatment in patients who have not reached their treatment goals after 12weeks. Additional benefits included improvements in PROs and reduction of concomitant glucocorticoids. ClinicalTrials.gov NCT02486302.

Iron Chelation in Patients with Myelodysplastic Syndromes and Myeloproliferative Neoplasms-Real-World Data from the German Noninterventional Study EXCALIBUR.

Myelodysplastic syndromes and myeloproliferative neoplasms both represent hematologic diseases associated with bone marrow failure often resulting in anemia. For those patients, transfusion of red blood cell (RBC) units is essential but results in iron overload (IOL) that may affect various organ functions. Therefore, iron chelation therapy plays a major role in anemic patients, not only because it reduces IOL, but also because it may improve hematopoietic function by increasing hemoglobin or diminishing the requirement for RBC transfusions. To assess the utility, efficacy, and safety of the different iron chelation medications approved in Germany, as well as to examine the effect of chelation on hematopoietic insufficiency, a prospective, multicenter, noninterventional study named EXCALIBUR was designed. In total, 502 patients from 106 German hospitals and medical practices were enrolled. A large proportion of patients switched from a deferasirox dispersible tablet to a deferasirox-film-coated tablet, mainly because of more convenient application, which was reflected in the treatment satisfaction questionnaire for medication scores. Iron chelation was effective in lowering serum ferritin levels, with the observed adverse drug reactions being in line with the known safety profile. Hematologic response occurred in a few patients, comparable to other studies that examined hematologic improvement in patients with MDS.

O-145 - Mogamulizumab in patients with mycosis fungoides or Sézary syndrome: interim analysis of the German non-interventional MINT study

O-145 - Mogamulizumab in patients with mycosis fungoides or Sézary syndrome: interim analysis of the German non-interventional MINT study

Etanercept is Effective and Halts Radiographic Progression in Rheumatoid Arthritis and Psoriatic Arthritis: Final Results from a German Non-interventional Study (PRERA).

Etanercept (ETN) has been shown to slow radiographic progression of rheumatoid arthritis (RA) and psoriatic arthritis (PsA) in clinical trials. This real-world, non-interventional study assessed radiographic progression in patients with RA or PsA treated with ETN for ≤ 36months in outpatient care in Germany (NCT01623752). Patients with RA or PsA attended ≤ 10 visits across two study phases (phase 1: seven visits, baseline to month 18; phase 2: three visits until month 36). Radiographs were taken at baseline (Rx1), months 12-18 (Rx2), and/or months 30-36 (Rx3). Historic radiographs (Rx0) taken 12-48months pre-baseline were also evaluated (if available). The primary endpoint was the change in modified total Sharp score (mTSS). The erosion score (ES) and joint space narrowing score (JSN) were also evaluated. Overall, 1821 patients were enrolled (RA: n = 1378; PsA: n = 440). In patients with Rx1 and Rx2 (RA: n = 511; PsA: n = 167), the mean mTSS remained stable for both disease groups, and the annualized median change in mTSS was 0. In patients with Rx0, Rx1, and Rx2 (RA: n = 180; PsA: n = 47), annualized radiographic progression in mTSS, ES, and JSN was larger in the pre-ETN treatment phase than during ETN treatment in both disease groups. The percentage of patients with radiographic non-progression was higher during ETN treatment versus pre-ETN. Improvement in clinical disease activity and patient-reported outcomes was also observed. This was the first real-world, non-interventional study to report systematically collected radiographic data in a large cohort of patients with RA or PsA under treatment with a biologic. In patients with available radiographic data, mean radiographic progression was lower and the proportion of patients without progression was greater during ETN treatment than in the pre-ETN period.

Dual HER2 blockade with pertuzumab (P) and trastuzumab (T) in patients with HER2-positive metastatic breast cancer (mBC) relapsing after adjuvant treatment with T: results from a German non-interventional study (NIS) HELENA (NCT01777958)

PurposeNIS HELENA documented outcomes in clinical routine practice of first-line therapy with P plus T and docetaxel (D) of patients with advanced HER2-positive BC and prior (neo)adjuvant T.MethodsBetween 06/2013 through 07/2016, 126 patients (in-label use of P at study start = full analysis set, FAS) in 81 German study sites were included. Intense documentation period was limited to 28 treatment cycles. Maximum follow-up (FU) was 24 months (mos). Safety was assessed in the safety set (SAF = eligible patients with at least one dose of P, n = 132). Median progression-free survival (PFS) was the main parameter of interest.ResultsMean age of FAS patients was 55.1 [30.7–80.2] years, 81.7% (95.2%) were < 65 (75) years of age. 51.6% of the FAS patients were hormone receptor-positive (HR+), 91.3% had distant, 73.0% visceral, and 18.3% non-visceral metastases. Median disease-free interval was 40.2 [6.6–95.9] mos. Effectiveness (FAS): Median PFS was 18.8 [15.1; 24.2] mos. Overall response rate was 64.3% (55.6; 72.1). Median overall survival was 55.9 mos [41.2, not reached]. Safety (SAF): 93.9% of patients had an adverse event (AE), 32.6% a serious AE (SAE). AEs related to P occurred in 53.8% of SAF, SAEs related to P in 13.6%. Diarrhea was the most frequently reported related (S)AE. There were 8 (6.1%) patients with a fatal AE.ConclusionBased on the outcomes from NIS HELENA, results of dual blockade with P+T in patients relapsing after (neo)adjuvant T as reported from the CLEOPATRA study (NCT01777958) can be transferred to routine clinical practice. No new safety signals were detected.

Abstract P2-13-16: Dual HER2-blockade with pertuzumab (P) and trastuzumab (T) in patients with HER2-positive metastatic breast cancer (mBC) relapsing after adjuvant treatment with T. Results from a German non-interventional study (NIS) HELENA (NCT01777958)

Abstract Background: Treatment of HER2 overexpressing mBC with the HER2 directed antibody combination of P and T became standard of care since marketing authorization of P based on the results of the randomized controlled CLEOPATRA trial (NCT 00567190). NIS HELENA was designed to document effectiveness and safety in clinical routine of first-line palliative therapy with P plus T and docetaxel (D) in patients with advanced HER2-positive BC after adjuvant therapy with T, and to determine whether the median PFS of 16.9 months (mos) reported for this subgroup in the CLEOPATRA trial can also be observed in day-to-day routine. Methods: Between 06/2013 through 07/2016, 126 patients with in-label use of P at study start (full-analysis set, FAS) in 81 German hospital-based or outpatient study sites were included into this NIS. Intense documentation period of this NIS was limited to 28 therapy cycles, and a follow-up (FU) for a maximum of 24 mos. Safety was assessed in all patients with at least one dose of P (safety set, SAF, n=132 ). QoL was assessed by FACT-B questionnaire. Main parameter of interest was mPFS. Patient Characteristics: Mean age of FAS patients was 55.1 [30.7 - 80.2] years, 81.7% (95.2%) were below 65 (75) years of age. 51.6% of the FAS patients were hormone-receptor positive (HR+), 91.3% patients of the FAS had distant, 69.8% had visceral, 45.2% liver metastases (VM). 89.7% patients of the FAS had R0-resection, including 44% breast conserving surgery, 42.9% of the FAS received neoadjuvant and 61.9% adjuvant chemo-/immunotherapy and 62.7% prior endocrine treatment. For the FAS median disease-free interval was 40.2 [6.6 - 95.9] mos. Effectiveness results: mPFS of FAS was 18.8 [15.1; 24.2] mos, longest mPFS was documented in patients with non-VM (20.5 [17.7, 27.7] mos), patients &amp;lt; 65 years (19.7 [15.4, 25.7] mos), and HR negative patients (19.4 [13.8, 27.7] mos). Overall response rate in the FAS was documented with 64.3% (55.6; 72.1], with best ORR in HR+ patients (69.2% [57.2, 79.1]), patients with VM (68.2%, [57.9, 77.0] and patients &amp;lt; 65 years (65% [55.5, 73.6]). 46 patients (36.5%) died during the study. Median OS was 55.9 mos [41.2, not reached] for the FAS. Safety: 93.9% of the SAF had an adverse event (AE), 32.6% a serious AE (SAE). AEs related to P occurred in 53.8% of SAF, SAEs related to P were documented in 13.6%. Diarrhea was the most frequently reported related (S)AE. Fatal AEs were seen in 6.1% of the SAF, in 2 patients related to P (death, central nervous system metastases and cerebral disorder). AEs leading to treatment discontinuation of any study product were observed in 20.5% of the SAF. During the intense documentation period, 11 patients had a LVEF &amp;lt;55%. QoL assessment using the total score index, increased slightly over time, however, based on declining patient response rates. Conclusion: Based on results from NIS HELENA, outcomes of pivotal CLEOPATRA study with respect to patients relapsing after adjuvant T pretreatment can be transferred into clinical routine. Patients derived benefit to a variable extent according to predefined subgroups. No new safety signals were detected. Citation Format: Marc Thill, Lead Auth., Andrea Grafe, Peter Klare, Kerstin Luedtke-Heckenkamp, Dietmar Reichert, Pauline Wimberger, Matthias Zaiss, Katja Ziegler-Loehr, Tanja Eckl, Andreas Schneeweiss. Dual HER2-blockade with pertuzumab (P) and trastuzumab (T) in patients with HER2-positive metastatic breast cancer (mBC) relapsing after adjuvant treatment with T. Results from a German non-interventional study (NIS) HELENA (NCT01777958) [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P2-13-16.

Effectiveness of Etanercept in Rheumatoid Arthritis: Real-World Data from the German Non-interventional Study ADEQUATE with Focus on Treat-to-Target and Patient-Reported Outcomes.

BackgroundFor rheumatoid arthritis (RA), the treat-to-target concept suggests attaining remission or at least low disease activity (LDA) after 12 weeks.ObjectivesThis German, prospective, multicenter, non-interventional study aimed to determine the proportion of patients with RA who achieved their treat-to-target aim after 12 and 24 weeks of etanercept (ETN) treatment in a real-life setting, as opposed to patients achieving their therapeutic target at a later timepoint (week 36 or 52).MethodsA total of 824 adults with a confirmed diagnosis of RA without prior ETN treatment were included. Remission and LDA were defined as DAS28 < 2.6 and DAS28 ≤ 3.2, respectively.ResultsThe proportion of patients achieving remission was 24% at week 12 and 31% at week 24. The proportion of patients achieving LDA was 39% at week 12 and 45% at week 24. The proportion of patients achieving remission or LDA further increased beyond week 24 up to week 52. Improvement in pain and reduction in concomitant glucocorticoid treatment were observed. Improvements in patient-reported outcomes were also seen in patients who did not reach remission or LDA. No new safety signals were detected.ConclusionsA considerable proportion of patients with RA attained the target of remission or LDA after 12 weeks of ETN treatment. Even beyond that timepoint, the proportion of patients achieving treatment targets continued to increase up to week 52.Trial RegistrationClinicalTrials.gov Identifier: NCT02486302.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40744-021-00418-5.

1079P Comparison of effectiveness and safety of nivolumab monotherapy or in combination therapy with ipilimumab in therapy-naïve and pretreated patients with advanced melanoma within the German noninterventional study NICO

Based on the first-line CheckMate 067 trial, nivolumab + ipilimumab (NIVO+IPI) has become a standard treatment in stage III/IV melanoma. However, limited data are available from prospective clinical trials on the effectiveness and tolerability of this combination in pretreated patients. Here, real-world data are presented especially for NIVO+IPI and also for NIVO in first and subsequent lines of therapy.

Quality of Life and Patient Reported Outcome (PRO) in Patients Receiving High and Moderate Emetogenic Chemotherapy (Ctx) - Results of a German Non-Interventional Study with NEPA - a Netupitant/Palonosetron Fixed Dose Combination

Introduction: NEPA is a fixed dose combination of the NK1-receptor antagonist (RA) netupitant and the 5-HT3-RA palonosetron and approved for prevention of chemotherapy-induced nausea and vomiting (CINV) in pts receiving cisplatin-based highly emetogenic (HEC) or moderately emetogenic Ctx (MEC). Data from one of the pivotal studies demonstrates the safety and efficacy of NEPA in antrazyklin (A)-cyclophosphamid based Ctx, a regime recently reclassified as HEC. Both drugs are frequently used in regimens for hematology pts. A German non-interventional study investigated NEPA's efficacy and impact on quality of life in adult cancer pts by patient-related outcomes (PRO) and physicians' personal assessment under real life conditions. Primary objective was the evaluation of quality of life (QoL) in adults receiving NEPA for CINV prevention. Secondary endpoints were efficacy and safety of NEPA.Methods: Open label, non-interventional, prospective, national, multicenter study that evaluates CINV prevention and patients' QoL with NEPA in pts receiving either HEC or MEC on up to 2 consecutive Ctx days for at least consecutive 3 cycles. QoL was evaluated by the validated FLIE questionnaires at the end of each Ctx cycle. Efficacy was documented by the treating physicians and via patient diaries for 3 Ctx cycles within 24 hours after and additional 4 days after chemotherapy. Safety, additional medication and physicians' overall satisfaction was reported via eCRF.Results: Between June 2015 and May 2017 a total of 1959 pts were enrolled with 1883 pts being eligible. 1846 pts were included in the efficacy analysis in the 1st, 1711 pts in the 2nd and 1600 pts in the 3rd cycle. Median age was 57 (range of 28-89). 55% received anthracyclin-based and 31% platinum based Ctx. Efficacy, evaluated by physicians' personal assessment on a 4-point scale, was rated very good or good for 1656 (89.7%), 1540 (90.0%) and 1469 (91.8%) patients in cycle 1, 2 and 3, respectively. At this stage, PRO with complete response was analyzed based on 293 completed diaries. Here, 83.9% reported no emesis and no rescue medication in the acute phase (0-24h post chemotherapy), while 78.5% and 74.0% reported complete response in the delayed (>24-120h post chemotherapy) and overall phase (0-120h post chemotherapy). A high percentage of patients did not suffer from any emesis (94%, 94% and 90% in the acute, delayed and overall phase, respectively). Over 90% of pts reported no impact on daily QoL due to vomiting in all 3 cycles with HEC or MEC.Conclusions: NEPA proved to be highly effective for prevention of CINV. Patient reported outcome was rated very good or good in more than 90% of patients in all three reported Ctx cycles in the acute as the delayed phase of highly and moderately emetogenic Ctx including platinum or anthracyclin based therapy. The physicians evaluation was concordant to PRO. DisclosuresKarthaus:HELSINN: Honoraria, Other: Travel grant; Riemser: Honoraria, Other: Travel grant. Schilling:Riemser: Honoraria, Other: Travel grant.

Characterisation of depressive symptoms in rheumatoid arthritis patients treated with tocilizumab during routine daily care.

To assess whether tocilizumab treatment is associated with changes in depression symptoms in patients with rheumatoid arthritis (RA) during routine daily care. We retrospectively analysed data from a German non-interventional study (ARATA) of adult, tocilizumab-naïve RA patients who initiated subcutaneous tocilizumab and were followed for 52 weeks. The Beck Depression Inventory II (BDI-II) was used to assess symptoms of depression and create baseline subgroups of no (BDI-II<14), mild (14-19), moderate (20-28), and severe (≥29) depression. Other key outcomes included Disease Activity Score-28 joints (DAS28), patient-reported outcomes (PROs), and adverse events. Mixed model repeated measures (MMRM) assessed the impact of DAS28 on BDI-II over time, and Pearson correlation analyses evaluated associations between changes from baseline. Of 474/1155 ARATA patients who completed the BDI-II at baseline, 47.7% had evidence of depression: 18.4% mild, 17.7% moderate, and 11.6% severe. 229 patients (48.3%) completed the BDI-II at both baseline and week 52. Two-thirds of patients with moderate or severe depression at baseline improved to a milder or no depression subgroup at week 52 (44/65 [67.7%]). Improvements in disease activity and PROs were observed in all subgroups, but patients with depression had lower response and higher adverse events rates. We observed an association between DAS28 and BDI-II over time in MMRM analyses, but the Pearson correlation for change from baseline was weak (r=0.10). Depression is common in patients receiving routine care for RA. Improvements in depressive symptoms in RA during tocilizumab therapy appear to be distinct from changes in disease activity.

1104P Nivolumab (NIVO) monotherapy or combination therapy with ipilimumab (NIVO+IPI) in advanced melanoma patients with brain metastases: Real-world evidence from the German non-interventional study NICO

Although melanoma brain metastases (MBM) have a relative incidence of 10%–40% in stage IV disease and often contribute directly to the cause of death, these patients are mostly excluded from prospective clinical studies due to their poor prognoses. Comparatively little is thus known about the effectiveness and tolerability of NIVO and NIVO+IPI in this vulnerable patient population, and real-world evidence for NIVO+IPI, a standard treatment option for MBM, is lacking for first and subsequent lines of therapy. NICO is a prospective, observational, multicenter study in Germany associated with ADOREG, assigned to enroll up to 750 patients with advanced melanoma who begin NIVO or NIVO+IPI treatment according to the marketing authorization. Patients will be followed for up to 5 years with assessments performed according to routine clinical practice. The primary objective is overall survival in patients receiving NIVO+IPI. Secondary objectives include overall survival in patients treated with NIVO, progression-free survival, safety profiles, adverse event management, treatment patterns, and patient-reported outcomes. Of all 623 patients (data cut 30/09/2019) enrolled with advanced melanoma, 64% received NIVO+IPI and 36% NIVO, compared with 74% and 27%, respectively, of patients with MBM (n = 175). NIVO+IPI was preferred over NIVO for patients with more advanced intracranial disease at baseline (MBM, 33.9 vs 21.1%) and who were younger (≤65 years, 62.1 vs 33.9%). For both treatment options, similar fractions of MBM patients were treated in the first (∼60%) and subsequent therapy lines (∼40%), with better responses for therapy-naïve patients (best overall response rate for NIVO+IPI, 31.0% vs 23.7%; NIVO, 26.9% vs 24%) by trend. The general safety profiles of both immuno-oncology therapies were confirmed. No new safety signals were observed. We present first real-world data from the second interim analysis of the NICO study in MBM patients treated with NIVO or NIVO+IPI in the first and subsequent treatment lines in routine care in Germany. Overall, both therapies provide effective and safe treatment options.

AB0817 DOES SMOKING AFFECT SECUKINUMAB TREATMENT OUTCOMES AND SAFETY IN PATIENTS WITH PSORIATIC ARTHRITIS? - REAL WORLD DATA FROM THE GERMAN AQUILA STUDY

Background:Several studies have shown a negative association between smoking status and psoriatic arthritis (PsA) clinical outcomes.1,2The German non-interventional study AQUILA provides real-world data on the influence of smoking on therapeutic effectiveness and safety issues under secukinumab (SEC), a fully human monoclonal antibody that selectively inhibits interleukin-17A.Objectives:The aim of this interim analysis is to describe selected baseline (BL) demographics, to evaluate SEC effectiveness on disease activity and depressive mood and to report the safety profile depending on smoking status of PsA patients.Methods:AQUILA is an ongoing, multi-center study including up to 2700 patients with active PsA or ankylosing spondylitis. Patients were observed from BL up to week (w) 52. Real-world data was assessed prospectively and analyzed as observed. In addition to the assessment of C-reactive protein (CRP), data was collected on patient´s disease activity (tender/swollen joint counts, TJC/SJC), skin disease activity (Psoriasis Area and Severity Index, PASI) and depressive mood (Beck´s Depression Inventory version II, BDI-II). For calculation of the proportion of patients who experienced (serious) adverse events ((S)AEs), all PsA patients were included who received at least one dose of SEC irrespective of further documentation of any study visit. This interim analysis focuses on subgroups non-smoker (NS) and smoker (S).Results:At BL, 641 PsA patients were included: 49.8% (n=319) non-smokers (NS) and 24.3% (n=156) smokers (S). 17.5% (n=112) were ex-smoker and 8.4% (n=54) of unknown smoking status. In both, NS and S, the proportion of women was higher (58.0% in NS and 67.3% in S). NS were slightly older than S (mean age: 53.8/49.7 years). There were no significant differences between NS and S in mean CRP within the 52 weeks (Fig. 1A). Both TJC and SJC improved over time and were similar between NS and S (Fig. 1B). Although mean absolute PASI value was worse in S at BL, a similar temporal improvement was seen in both groups (NS: 7.0 at BL to 1.0 at w52; S: 9.2 at BL to 1.0 at w52). BDI-II scores decreased in both groups with overall higher values in S (NS: 10.9 at BL to 9.1 at w52; S: 12.8 at BL and 10.8 at w52). Regarding the occurrence of AEs and SAEs with or without suspected relationship to SEC, NS had percentagewise less events than S (Table 1). In addition, percentage of PsA patients who discontinued SEC treatment due to an AE was lower for NS compared to S.Table 1.Overview of AEs (and SAEs) under SEC treatment depending on smoking status in PsA patientsNumber of patients withNS (N=333), n (%)S (N=161),n (%)P valueAE233 (70.0)118 (73.3)0.11AE with suspected relationship to SEC129 (38.7)72 (44.7)0.10SAE74 (22.2)45 (28.0)0.06SAE with suspected relationship to SEC29 (8.7)18 (11.2)0.37Figure 1.Disease activity in PsA patients treated with SEC depending on the smoking status**CRP data/ACR joint counts were documented not for all PsA patients at BL and subsequent visits.Conclusion:In a real-world setting, SEC improved disease activity and depressive mood of PsA patients with no obvious differences between NS and S. Overall, this interim analysis shows that SEC is an effective and reliable treatment, irrespective of the PsA patients’ smoking status. Further progress of the AQUILA study as well as long-term data from other real-world observational studies with SEC, such as SERENA, will reveal whether this trend will continue.

1536P - Patients with brain metastases treated with afatinib in clinical practice: Results from the prospective non-interventional study GIDEON

BackgroundThe presence of brain metastases is a negative prognostic factor for non-small cell lung cancer (NSCLC) patients, which are therefore frequently excluded from clinical trials. A competing risk analysis from the Lux Lung trials showed that afatinib delayed the onset/progression of brain metastases. In Lux Lung 3 patients with brain metastases revealed a median PFS of 11.1 months when treated with afatinib vs. 5.4 months with chemotherapy (HR=0.54). MethodsThe prospective German non-interventional real world study GIDEON enrolled 151 advanced NSCLC adenocarcinoma patients with activating EGFR mutations treated with afatinib according to label. Here, we report results of the first interim analysis and focus on patients with brain metastases at baseline. ResultsPatients with brain metastases accounted for 32% of the GIDEON study population (n=49/151). Overall response rate (ORR) and disease control rate (DCR) in patients with brain metastases were 74% and 91% (n=35), which was similar to patients without brain metastases (ORR: 73%, DCR: 90%, n=59). However, PFS rate at one year was 43% in patients with brain metastases and 60% in patients without brain metastases. Median PFS was 11 months in patients with brain metastases (n=48, 95% CI 9.18- 13.88) and 16 months in patients without brain metastases (n=94, 95% CI 10.95- 19.57). Overall survival was not mature at the time of this analysis. ConclusionsPresence or absence of brain metastases had no influence on the response rate or disease control rate with afatinib. However, patients with brain metastases had shorter PFS than patients without brain metastases, confirming their negative prognostic impact. Taken together, these data underline the efficacy of afatinib and support its use in patients with brain metastases. Clinical trial identificationNCT02047903. Legal entity responsible for the studyBoehringer Ingelheim. FundingBoehringer Ingelheim. DisclosureC. Hoffmann: Full / Part-time employment: Boehringer Ingelheim. M. Reck: Honoraria (self), Advisory / Consultancy: Abbot; Honoraria (self), Advisory / Consultancy: AstraZeneca; Honoraria (self), Advisory / Consultancy: BMS; Honoraria (self), Advisory / Consultancy: Boehringer Ingelheim; Honoraria (self), Advisory / Consultancy: Celgene; Honoraria (self), Advisory / Consultancy: MSD; Honoraria (self), Advisory / Consultancy: Merck; Honoraria (self), Advisory / Consultancy: Novartis; Honoraria (self), Advisory / Consultancy: Pfizer; Honoraria (self), Advisory / Consultancy: Roche; Honoraria (self), Advisory / Consultancy: Amgen. C. Kortsik: Travel / Accommodation / Expenses: Boehringer Ingelheim. F. Griesinger: Honoraria (self), Advisory / Consultancy: AbbVie; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): BMS; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Boehringer Ingelheim; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Celgene; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): MSD; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Lilly; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Novartis; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Pfizer; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Roche; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Takeda; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Siemens; Honoraria (self), Advisory / Consultancy: Bayer. A. Schueler: Full / Part-time employment: Boehringer Ingelheim. W. Brückl: Advisory / Consultancy: AbbVie; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: BMS; Advisory / Consultancy: Boehringer Ingelheim; Advisory / Consultancy: Celgene; Advisory / Consultancy: Chugai; Advisory / Consultancy: Lilly; Advisory / Consultancy: MSD; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Roche; Advisory / Consultancy: Stratifyer. All other authors have declared no conflicts of interest.

576P - Impact of prophylactic systemic antibiotics (SA) on outcome of patients (pts) with RAS-wildtype (RAS-wt) metastatic colorectal carcinoma (mCRC) treated with cetuximab-based first-line therapy. Subgroup analysis of the german non-interventional study ERBITAG

BackgroundSA are widely used and recommended to ameliorate skin reactions induced by EGFR inhibition. Randomised studies have shown a positive impact of SA on severity of skin reactions, but the influence on outcome are widely unknown. Recent data suggests that antibiotics negatively influence the efficacy of checkpoint-inhibitor therapies. Therefore, an evaluation of the impact of SA on the outcome of RAS-wt mCRC pts treated with cetuximab-based therapy is highly needed. MethodsPts with RAS-wt mCRC treated with a cetuximab-based first-line combination and written informed consent were eligible for this prospective, non-interventional study. According to a thorough questionnaire about prophylactic treatments for skin management, pts were categorized in 2 groups: SA and no SA. Outcome endpoints like objective remission rate (ORR), progression free survival (PFS), overall survival (OS), and time to treatment failure (TTF) were compared between the two subgroups. ResultsData from 583 of 875 enrolled pts were evaluable at the data cut-off (SA: n=183; no SA: n=400). Pts were not included for the following reasons: no cetuximab therapy (34), not fully documented (131), no first-line therapy (95), no RAS-wt (2), and no skin questionnaire (30). Pts in the SA group showed compared to the no SA group a significantly increased median PFS with 12.30 vs 9.51 months (p=0.033) and OS with 28.22 vs. 20.79 months (p=0.0063). Number of cetuximab infusions were numerically higher in the SA group (mean: 30.6 vs 27.4, p=0.0581), as well as ORR with 63.9% and 56.5% (p=0.09) and TTF with 5.46 vs 4.61 months (p=0.0746), but all three endpoints did not reach significance. In a multivariate analysis the impact of SA was an independent significant factor on OS (p<0.05), but not on PFS (p=0.09). ConclusionsData of this large non-interventional trial suggests that SA have a positive impact on the OS outcome of RAS-wt mCRC pts treated with a cetuximab-based first-line therapy. Hence, the data supports the recommendations for SA in the treatment management of EGFR inhibitors in mCRC. Editorial acknowledgementFelix Eilenberger, Alcedis GmbH, Gießen, Germany. Legal entity responsible for the studyMerck Serono GmbH, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany. FundingMerck Serono GmbH, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany. DisclosureS.W. Sahm: Shareholder / Stockholder / Stock options: Merck KGaA; Honoraria (self): Fresenius Kabi; Research grant / Funding (institution): Merck Serono GmbH. M. Zahn: Honoraria (self): Merck Serono GmbH. J. Janssen: Advisory / Consultancy, Research grant / Funding (self): Bayer; Advisory / Consultancy: Boehringer Ingelheim; Advisory / Consultancy, Research grant / Funding (institution): Bristol-Myers Squibb; Advisory / Consultancy, Research grant / Funding (institution): Novartis; Advisory / Consultancy, Research grant / Funding (institution): Roche; Advisory / Consultancy, Research grant / Funding (institution): Sanofi; Advisory / Consultancy, Research grant / Funding (institution): PharmaMar; Research grant / Funding (institution): Amgen; Research grant / Funding (institution): Onyx; Research grant / Funding (institution): Baxter; Research grant / Funding (institution): Biotest; Research grant / Funding (institution): Celgene; Research grant / Funding (institution): Janssen Cilag Ltd; Research grant / Funding (institution): Kedrion Biopharma; Research grant / Funding (institution): Eli Lilly; Research grant / Funding (institution): Merck Serono GmbH; Research grant / Funding (institution): Octapharma; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Puma Biotechnology; Research grant / Funding (institution): Teva Pharmaceutical; Research grant / Funding (institution): AbbVie; Research grant / Funding (institution): Ipsen; Research grant / Funding (institution): Servier. C. Hering-Schubert: Honoraria (self): Novartis; Honoraria (self), Advisory / Consultancy: Amgen; Honoraria (self): Sanofi. I. Zander: Advisory / Consultancy: Boehringer Ingelheim; Honoraria (self): Pfizer; Honoraria (self): Mundipharma; Travel / Accommodation / Expenses: Bristol-Myers Squibb; Travel / Accommodation / Expenses: Novartis; Travel / Accommodation / Expenses: Ribosepharm; Travel / Accommodation / Expenses: Merck Serono GmbH. K.G. Stenzel: Full / Part-time employment: Merck Serono GmbH; Shareholder / Stockholder / Stock options: Merck KGaA. F. Overkamp: Leadership role, Full / Part-time employment: OncoConsult. Hamburg GmbH; Leadership role, Full / Part-time employment: onkowissen.de GmbH; Honoraria (self), Advisory / Consultancy: Amgen; Honoraria (self), Advisory / Consultancy: Bayer; Honoraria (self): AstraZeneca; Honoraria (self), Advisory / Consultancy: Bristol-Myers Squibb; Honoraria (self), Advisory / Consultancy: Boehringer Ingelheim; Advisory / Consultancy: Cellex; Advisory / Consultancy: ClinSol; Honoraria (self), Advisory / Consultancy: Gilead; Advisory / Consultancy: Hexal; Honoraria (self), Advisory / Consultancy: Iomedico; Honoraria (self), Advisory / Consultancy: Merck Sharp & Dohme; Honoraria (self), Advisory / Consultancy: Novartis; Honoraria (self), Advisory / Consultancy: Riemser; Advisory / Consultancy: Roche; Advisory / Consultancy: Tesaro; Advisory / Consultancy: Teva; Honoraria (self): Chugai; Honoraria (self): Celgene; Honoraria (self): Eisai; Honoraria (self): Ipsen; Honoraria (self): Janssen-Cilag; Honoraria (self): Merck Serono GmbH; Honoraria (self): Novo Nordisc; Honoraria (self): Servier; Honoraria (self): Shire. All other authors have declared no conflicts of interest.

Abstract P6-18-08: Everolimus + exemestane for HR+ advanced breast cancer in routine clinical practice- Final results from the non-interventional trial, BRAWO

Abstract Background: In the pivotal BOLERO-2 trial, everolimus (EVE) + exemestane (EXE) more than doubled the median progression-free survival (PFS) vs EXE alone in hormone receptor positive (HR+), human epidermal growth factor-receptor 2-negative (HER2-) advanced breast cancer (ABC) recurring/progressing on/after prior non-steroidal aromatase inhibitors (NSAIs). BRAWO is a German non-interventional study conducted in patients (pts) with HR+, HER2–ABC receiving EVE + EXE, according to Summary of Product Characteristics (SmPC), in routine clinical practice. Here we report the final PFS and safety results. Methods: This multicenter study documented 2100 pts between October 2012 and December 2017 across 341 sites in Germany. Postmenopausal women with HR+, HER2– ABC with recurrence or progression after a NSAI were included. Primary observation parameters included the evaluation of the effectiveness of EVE + EXE used in routine care for the entire pt group. Results: In the final analysis, out of the 2100 documented pts, 2074 were included in the full analysis set. The median time since the primary diagnosis was 7.1 years and the median time from first sign of relapse (local recurrence or distant metastases) was 2.1 years. At baseline, 54.1% of pts presented with visceral metastases and 50.1% had an ECOG performance status of 0. Approximately, 63% of pts started with EVE 10 mg (median duration of exposure: 5.1 months; 95% CI, 4.6-5.4), while 34.1% started with EVE 5 mg (median duration of exposure: 4.6 months; 95% CI, 4.1-5.2). The distribution of treatment lines was as follows: first line, 28.7% (n=595); second line, 31.9% (n=662); third line, 18.1% (n=376); fourth line, 10.7% (n=221) and, fifth line and later, 10.6% (n=220). Treatment was discontinued by 55.7% of pts (n=1170) due to progressive disease and 26% of pts (n=546) due to adverse events. The Kaplan-Meier estimate of the median PFS was 6.6 months (95% CI, 6.2-7.0). The best overall responses, based on clinical routine, were complete response, 0.8% (n=17), partial response, 7.4% (n=150), and stable disease, 41.3% (n=842). The general safety profile was consistent with the previously reported safety findings. The most common adverse events were stomatitis (any grade: 42.6%, grade 3: 3.8%, grade 4: &amp;lt;0.1%) and fatigue (any grade: 19.8%, grade 3: 1.5%). Conclusions: Data from BRAWO support EVE + EXE as a suitable treatment option with a reasonable safety profile for HR+, HER2− ABC recurring or progressing on/after prior NSAIs. Citation Format: Lüftner D, Schuetz F, Schneeweiss A, Grischke E-M, Bloch W, Decker T, Uleer C, Salat C, Förster F, Schmidt M, Mundhenke C, Tesch H, Jackisch C, Fischer T, Guderian G, Hanson S, Fasching P. Everolimus + exemestane for HR+ advanced breast cancer in routine clinical practice- Final results from the non-interventional trial, BRAWO [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P6-18-08.

Bevacizumab plus IFN-alpha-2a in First-line Treatment of Patients With Advanced or Metastatic Renal Cell Carcinoma: A Prospective German Non-interventional Study.

The combination of bevacizumab (BEV) plus interferon alpha-2a (IFN) constitutes an option for first-line treatment of metastatic renal cell carcinoma. Real-world data from routine clinical practice are rare and were, therefore, collected during this non-interventional study (NIS). A total of 359 patients received at least one dose of BEV (safety set population; SAF), 354 patients had at least one post-dose effectiveness assessment and formed the full analysis set (FAS) of the final analysis. Progression-free survival (10.2 months, 95% CI=8.6-12.6) and overall response rate (27.2%) outcomes match the results from the phase III trials AVOREN and CALGB 90206. Longer overall survival (28.7 months, 95% CI=24.5-38.3) probably is an effect of patient characteristics and follow-up therapies. Safety findings were comparable to the results of the Phase III trials, although comprehensive severity assessments were not provided. Overall, efficacy and safety data from BEV plus IFN administered in routine clinical practice in an observational NIS are in line with results from the controlled phase III trials. (NCT02627144).