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Introduction Invasive lobular breast cancer (ILC) is with 5-10% the second most common histologic type of invasive breast cancer after invasive ductal breast cancer (IDC). ILC differs from IDC, for example in its metastatic pattern. However, guidelines do not provide special treatment recommendations for this subtype and specific clinical studies are rare. Here we present prospective data on characteristics, treatment and outcome of patients (pts) with advanced ILC in routine care in Germany. Methods The Tumor Registry Breast Cancer (TMK) has prospectively documented data of pts with breast cancer by oncologists in Germany since 2007. Since 2017 OPAL continues the TMK work with representation of all specialists (medical and gynecologic oncologists) treating advanced breast cancer (ABC). Both projects are prospective, observational, open, longitudinal multicenter cohort studies (clinical registries). Pts at the start of their treatment can be included after signing informed consent. Together over 7500 pts (4250 with ABC) will be recruited from over 150 sites in Germany. There is no treatment specification. Details on all (sequential) treatments, patient and tumor characteristics, clinical and patient-reported outcomes are documented. Follow-Up is until death or up to 5 years. Here, data as of March, 31st 2020 are presented. Results Pts with advanced ILC (n=372) were older at start of first-line treatment (median 68 vs. 63 years) while ECOG performance status (ECOG 0 25% vs 29%) and Charlson Comorbidity Index (CCI 0: 82% vs 84%) were similar compared to pts with IDC (n=1745). The lobular tumor was more often hormone receptor (HR) positive (87% vs 74%) and less often HER2 positive (14% vs 27%). The percentage of primary metastatic disease (M1) was 34% in both groups, while grade at diagnosis was more frequently G1/2 in the ILC group (73% vs 51%). The metastatic pattern was more often non-visceral only for the ILC group (26% vs 19%), and metastases were found more often in bone (52% vs 42%) and peritoneum (9% vs 2%) and less often in liver (20% vs 25%) and lung (7% vs 25%). Overall, pts with ILC were treated more often with endocrine therapy (ET) +/- CDK4/6-inhibitors (CDK4/6i) than pts with IDC (52% vs 33%), yet, ILC is more often HR-positive than IDC. Of pts receiving chemotherapy (CT) 53% of ILC and 56% of IDC tumors were treated with taxanes as first-line treatment. 20% of ILC vs. 24% of IDC tumors received a combination-CT. First-line treatment strategy was analyzed for the HR-positive, HER2-negative subgroup. From 2007-16 pts with ILC received more often ET (ILC (n=162) 54% vs IDC (n=696) 44%), while IDC were more often treated with CT first-line. Since approval of CDK4/6i, distribution of treatment strategies has been quite similar (ILC (n=123): CDK4/6i: 76%, ET: 15%, CT: 10% and IDC (n=311): CDK4/6i: 72%, ET: 12%, CT: 15%). Overall survival (OS) from start of first-line treatment was estimated for all pts recruited by 2016 (follow-up of at least 3 years). Median OS was comparable: ILC (n=224) 30.6 months (68% events, 95%-CI 26.1 - 36.9 months) and IDC (n=1217) 34.1 months (60% events, 95%-CI 30.6 - 38.4 months). For the HR-positive, HER2-negative subgroup, OS was also similar. A multivariate regression analysis on factors affecting OS will be presented. Conclusion Registries, like TMK/OPAL, can provide data on rare tumor subtypes. We show that ABC with an invasive lobular histology differs in receptor status (more often HR-positive) and metastatic pattern (e.g. more often non-visceral) from the invasive ductal subtype. Nevertheless, treatment strategies for first-line treatment are similar and median OS is comparable despite ILC pts being markedly older. Future research should focus on identifying pts who could benefit from personalized treatment approaches including tumor subtype as a factor to consider. Citation Format: Marc Thill, Mark-Oliver Zahn, Anja Welt, Elmar Stickeler, Arnd Nusch, Thomas Fietz, Jacqueline Rauh, Natalie Wetzel, Lisa Kruggel, Martina Jänicke, Norbert Marschner, Nadia Harbeck, Achim Wöckel, Thomas Decker, OPAL study group. Rare patients in routine care: Treatment and outcome in advanced invasive lobular breast cancer in the prospective German research platform OPAL [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS11-16.

Objectives An increasing number of treatment-determining biomarkers has been identified in non-small cell lung cancer (NSCLC) and molecular testing is recommended to enable optimal individualized treatment. However, data on implementation of these recommendations in the “real-world” setting are scarce. This study presents comprehensive details on the frequency, methodology and results of biomarker testing of advanced NSCLC in Germany. Patients and methods This analysis included 3,717 patients with advanced NSCLC (2,921 non-squamous; 796 squamous), recruited into the CRISP registry at start of systemic therapy by 150 German sites between December 2015 and June 2019. Evaluated were the molecular biomarkers EGFR, ALK, ROS1, BRAF, KRAS, MET, TP53, RET, HER2, as well as expression of PD-L1. Results In total, 90.5 % of the patients were tested for biomarkers. Testing rates were 92.2 % (non-squamous), 70.7 % (squamous) and increased from 83.2 % in 2015/16 to 94.2% in 2019. Overall testing rates for EGFR, ALK, ROS1, and BRAF were 72.5 %, 74.5 %, 66.1 %, and 53.0 %, respectively (non-squamous). Testing rates for PD-L1 expression were 64.5 % (non-squamous), and 58.5 % (squamous). The most common testing methods were immunohistochemistry (68.5 % non-squamous, 58.3 % squamous), and next-generation sequencing (38.7 % non-squamous, 14.4 % squamous). Reasons for not testing were insufficient tumor material or lack of guideline recommendations (squamous). No alteration was found in 37.8 % (non-squamous), and 57.9 % (squamous), respectively. Most common alterations in non-squamous tumors (all patients/all patients tested for the respective biomarker): KRAS (17.3 %/39.2 %), TP53 (14.1 %/51.4 %), and EGFR (11.0 %/15.1 %); in squamous tumors: TP53 (7.0 %/69.1 %), MET (1.5 %/11.1 %), and EGFR (1.1 %/4.4 %). Median PFS (non-squamous) was 8.7 months (95 % CI 7.4–10.4) with druggable EGFR mutation, and 8.0 months (95 % CI 3.9–9.2) with druggable ALK alterations. Conclusion Testing rates in Germany are high nationwide and acceptable in international comparison, but still leave out a significant portion of patients, who could potentially benefit. Thus, specific measures are needed to increase implementation.

There is no prospective, randomised head-to-head trial comparing first-line FOLFIRINOX and gemcitabine/nab-paclitaxel in advanced pancreatic cancer. We assess real-world effectiveness and quality of life (QoL) of both regimens using a new prognostic score. This analysis includes 1540 patients with advanced pancreatic cancer from the prospective, clinical cohort study Tumour Registry Pancreatic Cancer separated into learning (n = 1027) and validation sample (n = 513). The Pancreatic Cancer Score (PCS) was developed using multivariate Cox regression. We compared overall survival (OS) and time to deterioration (TTD) for longitudinal QoL between first-line FOLFIRINOX (n = 407) and gemcitabine/nab-paclitaxel (n = 655) according to patients' prognostic risk, after inverse probability of treatment weighting (IPTW) by propensity score analysis. The PCS includes nine independent prognostic factors for survival: female sex, BMI ≥24/unknown, ECOG performance status ≥1, Charlson comorbidity index ≥1, tumour staging IV/unknown at primary diagnosis, liver metastases, bilirubin1.5× upper limit of normal (ULN), leukocytesULN and neutrophil-to-lymphocyte ratio ≥4. Median OS of the validation sample was 11.4 (95% confidence interval [CI]: 10.4-14.4), 8.5 (95% CI: 6.8-9.6) and 5.9 months (95% CI: 4.0-7.4) for favourable- (0-3 risk factors), intermediate- (4-5 factors) and poor-risk group (6-9 factors), respectively. After IPTW, only poor-risk patients had significantly longer median OS and TTD of overall QoL with FOLFIRINOX (OS: 6.9 months, 95% CI: 3.9-13.3; TTD: 10.6 months, 95% CI: 2.0-14.1) vs gemcitabine/nab-paclitaxel (OS: 4.0 months, 95% CI: 2.8-4.8; TTD: 4.1 months, 95% CI: 2.4-4.5). Our novel PCS may facilitate treatment decisions in clinical routine of advanced pancreatic cancer, since only poor-risk, but not favourable-risk patients, seem to benefit from intensified treatment with FOLFIRINOX.

ZusammenfassungÜber Register können Fragestellungen zur Gesundheitsversorgung im Alltag untersucht werden. Sie sind daher eine wesentliche Methode der Versorgungsforschung. Das Deutsche Netzwerk Versorgungsforschung (DNVF) fördert die Qualität von Registern durch einen wissenschaftlichen Austausch, durch Fortbildungsangebote sowie durch Empfehlungen in Form eines Memorandums „Register für die Versorgungsforschung“. Die vorliegenden Empfehlungen stellen ein Update zur ersten Fassung des Memorandums von 2010 dar. Das Update beschreibt die Einsatzmöglichkeiten und Zielsetzungen von Registern in der Versorgungsforschung und stellt den aktuellen Stand zu allen Aspekten eines guten Designs und eines sachgerechten Betriebs von Registern dar. Das Memorandum kann Verantwortlichen für die Entwicklung eines Registers als Leitfaden zur Erreichung einer hohen Qualität dienen; potentiellen Nutzern von Daten und Ergebnissen aus Registern ermöglicht es, die Qualität eines Registers zu bewerten. Projektförderer und Gesundheitspolitik können sich bei der Rahmensetzung für Finanzierung und gesetzliche Anforderungen an den Qualitätskriterien orientieren. Neben einer Definition werden im Memorandum verschiedene für die Konzeption eines Registers relevante Bereiche vorgestellt. Dies umfasst die Phasen der Entwicklung eines Registers von der Planung über den Entwurf bis zur Umsetzung, die technische Organisation und den Betrieb eines Registers, die Auswertung von Registerdaten, die Berichterstattung über die Ergebnisse sowie den Datenschutz. Aus diesen Bereichen abgeleitete Kriterien zur Beurteilung der Qualität eines Registers werden beschrieben. Hierfür wird abschließend eine Checkliste präsentiert.

Introduction Tumor Registries give insight into routine treatment and complement the knowledge derived from randomized controlled trials (RCT), since characteristics of patients from RCTs often differ from those of patients in routine care. Furthermore, follow-up of patients in registries is generally longer which gives the possibility to analyze sequential treatments. Since 2007 the Tumor Registry Breast Cancer (TMK, NCT01351584) has prospectively collected data on treatment and outcome of patients with breast cancer in Germany. Among other topics, insights into “real-world” treatment and outcome and long-term observation of quality of life have been published. Since 2017 the registry platform OPAL (NCT03417115) has extended the work of the TMK by recruiting patients with advanced breast cancer (ABC) from all specialties (medical and gynecologic oncologists). The main aims are to observe the impact of novel treatments on patient outcome, and to identify areas for improvement of quality of care. Methods OPAL started in December 2017. Patients are prospectively recruited at start of their first systemic treatment for ABC. Follow-up continues until death or up to 5 years. There is no treatment specification. Detailed information on all (sequential) treatments, patient and tumor characteristics, physician-reported factors regarding treatment decision making, biomarker testing, outcomes (e.g. best response, progression-free and overall survival) are collected in a web-based data capture system with implemented checks for completeness and plausibility. Data are monitored by data management and on-site. Patient-reported outcomes (PROs) are collected at start of treatment and every 3 months thereafter. Patients can also give informed consent for their tumor samples to be used in future translational research (virtual biobank). All patient data remain in Germany. Here, first combined data from the TMK and OPAL (database as of 01.04.2019) are presented. Results Since 2007, 5076 patients have been recruited. Patients with ABC (n=2105, 434 since the start of OPAL) have a median age of over 60 years at start of treatment; about 60% have comorbidities. For patients with hormone-receptor positive (HRpos)/HER2 negative (HER2neg) ABC, first-line treatment has changed over the years. From 2007-11 (n=458) 60% of patients started with chemotherapy, decreasing to 48% in 2012-16 (n=528) and to 23% in 2018-19 (n=170) with 58% of patients now being treated with CDK4/6-inhibitor. First-line of HER2pos ABC has also changed from 79% of patients receiving trastuzumab (TRA) between 2007-12 (n=268) to 78% of patients receiving dual-blockade with TRA/pertuzumab in 2018-19 (n=97) and 10% receiving TRA only. About 25% of patients treated with TRA in 2018-19 received a biosimilar. Median overall survival (OS) of patients with start of first-line therapy between 2007-16 is currently 15 months for triple-neg (74% events), 34 months for HRpos/HER2neg (59% events), 40 months for HER2pos (52% events); median OS has not yet been reached for patients in OPAL. Conclusions For patients with HRpos/HER2neg ABC, a shift towards more endocrine therapy in the first-line setting, and a quick implementation of CDK4/6-inhibitors after their approval can be observed. In patients with HER2pos ABC, integration of trastuzumab biosimilars into routine care has started. Prognosis for patients with triple-negative ABC remains poor and new treatment options are urgently needed. OPAL together with TMK will allow to follow changes in treatment of patients with ABC in a “real world” setting in Germany, the application of sequential treatments, and their impact on clinical as well as patient-reported outcome. Citation Format: Elmar Stickeler, Nadia Harbeck, Marc Thill, Arnd Nusch, Marco Chiabudini, Lisa Kruggel, Martina Jänicke, Norbert Marschner, Mark-Oliver Zahn, Anja Welt, Achim Wöckel, Thomas Decker, OPAL Study Group. Therapy of advanced breast cancer for patients with hormone receptor-positive/HER2-negative and HER2-positive tumors is changing in real life: First results from the prospective, national research platform OPAL for patients with advanced breast cancer in Germany [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-17-01.

Non‐clear cell renal cell carcinoma is a very rare malignancy that includes several histological subtypes. Each subtype may need to be addressed separately regarding prognosis and treatment; however, no Phase III clinical trial data exist. Thus, treatment recommendations for patients with non‐clear cell metastatic RCC (mRCC) remain unclear. We present first prospective data on choice of first‐ and second‐line treatment in routine practice and outcome of patients with papillary mRCC. From the prospective German clinical cohort study (RCC‐Registry), 99 patients with papillary mRCC treated with systemic first‐line therapy between December 2007 and May 2017 were included. Prospectively enrolled patients who had started first‐line treatment until May 15, 2016, were included into the outcome analyses (n = 82). Treatment was similar to therapies used for clear cell mRCC and consisted of tyrosine kinase inhibitors, mechanistic target of rapamycin inhibitors and recently checkpoint inhibitors. Median progression‐free survival from start of first‐line treatment was 5.4 months (95% confidence interval [CI], 4.1–9.2) and median overall survival was 12.0 months (95% CI, 8.1–20.0). At data cutoff, 73% of the patients died, 6% were still observed, 12% were lost to follow‐up, and 9% were alive at the end of the individual 3‐year observation period. Despite the lack of prospective Phase III evidence in patients with papillary mRCC, our real‐world data reveal effectiveness of systemic clear cell mRCC therapy in papillary mRCC. The prognosis seems to be inferior for papillary compared to clear cell mRCC. Further studies are needed to identify drivers of effectiveness of systemic therapy for papillary mRCC., What's new? Over the past decade, the treatment landscape for locally advanced or metastatic renal cell carcinoma (mRCC) has dramatically changed. To date, however, guideline recommendations mainly address patients with clear cell mRCC, due to a lack of prospective Phase III evidence for the rarer, non‐clear cell mRCC subtypes. This is the first longitudinal, prospective cohort study evaluating treatment and survival of patients with papillary mRCC outside a prospective clinical trial setting. The presented real‐world data help bridge the evidence gap by revealing the frequent use and effectiveness of systemic clear cell mRCC therapy in papillary mRCC, with a seemingly inferior prognosis.

Objectives Despite intensive research, the therapeutic options in extensive-stage small cell lung cancer (SCLC) are still limited. Data from routine clinical practice, so-called “real-world data”, are centrally important to assess and improve the standard of care. We present prospectively documented data on systemic first-, second- and third-line treatment, number of treatment lines and outcome parameters of patients treated by medical oncologists in Germany. Materials and methods This is a descriptive analysis on 432 patients with extensive-stage SCLC enrolled at start of first-line therapy into the prospective German clinical cohort study TLK (Tumour Registry Lung Cancer). Patients were recruited by 87 sites between February 2010 and December 2013 and followed-up individually for 3 years. Results The majority of patients (93%) received a first-line platinum-based combination therapy. Carboplatin plus etoposide was documented more frequently than cisplatin plus etoposide (46 vs. 35%); patients receiving carboplatin were older (68 vs. 63 years) and more often presented with poorer performance status (17 vs. 11% ECOG ≥ 2). Both regimens yielded similar response and survival rates. Median first-line overall survival (OS) was 10.2 months (95% confidence interval [CI] 8.6–12.3) for carboplatin plus etoposide and 12.2 months (95% CI 10.1–14.7) for cisplatin plus etoposide. Most patients (77%) would have been eligible for participation in a clinical trial. 50% of the patients received a second and 22% a third line of treatment. Median second-line OS was 5.8 months (95% CI 4.8–7.5), median third-line OS 5.7 months (95% CI 3.8–7.0). Conclusion To our knowledge, this is the first study of prospectively documented patients with extensive-stage SCLC in routine clinical practice. We present treatment algorithms as well as outcome parameters for a large cohort in first-, second- and third-line treatment. The survival times and response rates reported in this routine setting correspond to the respective measures from large prospective trials.

Purpose Quality of life (QoL) plays an important role in recovery—especially after an incisive diagnosis such as breast cancer. Here, we present a comprehensive assessment of QoL for pre- and postmenopausal patients, starting from initial systemic treatment of early breast cancer until 3 years later, in patients from a so-called “real-world” setting. Methods 251 premenopausal and 478 postmenopausal patients with early breast cancer have been recruited into the longitudinal MaLife project within the prospective, multicentre, German Tumour Registry Breast Cancer between 2011 and 2015. The questionnaires FACT-G, FACT-Taxane, FACT-ES, EORTC QLQ-BR23, BFI and HADS were filled in at start of treatment (T0), 6, 12, 24 and 36 months later. The proportion of patients with clinically meaningful changes at 36 months was determined. Results This first interim analysis shows that the FACT-G global QoL improved over time regardless of the menopausal status. However, clinically meaningful decrease of social/family well-being (48–51%), arm symptoms (44–49%) and symptoms of neurotoxicity (55–56%) was frequently reported 3 years after start of treatment. Many premenopausal patients also reported a clinically meaningful worsening of endocrine symptoms (64%), emotional well-being (36%) and fatigue intensity (37%). Additionally, 3 years after start of treatment, 15% of the patients were classified as doubtful cases and 18% as definite cases of anxiety. Conclusions Despite improvements in global QoL, breast cancer survivors report worsened ailments 3 years after start of therapy. Follow-up care should distinguish between premenopausal patients needing special attention for emotional/menopausal issues, and postmenopausal patients needing particular care regarding physical concerns. Electronic supplementary material The online version of this article (10.1007/s10549-019-05197-whttps://doi.org/10.1007/s10549-019-05197-w) contains supplementary material, which is available to authorized users.

Objectives: After decades of unsuccessful efforts in inhibiting KRAS, promising clinical data targeting the mutation subtype G12C emerge. Since little is known about outcome with standard treatment of patients with G12C mutated non-small cell lung cancer (NSCLC), we analyzed a large, representative, real-world cohort from Germany. Patients and methods: A total of 1039 patients with advanced KRAS-mutant or -wildtype NSCLC without druggable alterations have been recruited in the prospective, observational registry CRISP from 12/2015 to 06/2019 by 98 centers in Germany. Details on treatment, best response, and outcome were analyzed for patients with KRAS wildtype, G12C, and non-G12C mutations. Results: Within the study population, 160 (15.4 %) patients presented with KRAS G12C, 251 (24.2 %) with non-G12C mutations, 628 (60.4 %) with KRAS wildtype. High PD-L1 expression (Tumor Proportion Score, TPS > 50 %) was documented for 28.0 %, 43.5 %, and 28.9 % (wildtype, G12C, non-G12C) of the tested patients; 68.8 %, 89.3 %, and 87.7 % of the patients received first-line treatment combined with an immune checkpoint-inhibitor in 2019. TPS > 50 % vs. TPS < 1 % was associated with a significantly decreased risk of mortality in a multivariate Cox model (HR 0.39, 95 % CI 0.26−0.60, p=

Background Guidelines for metastatic non-small cell lung cancer recommend stratified treatment by biomarker test results. We used CRISP to evaluate treatment and outcome of patients (pts) with targetable molecular alterations. Methods Currently 163 sites in Germany have recruited >3700 pts at start of 1st-line who will be followed until death or end of project. Data from 2204 pts recruited by 133 sites from 12/2015 to 06/2018 was analyzed. Progression-free survival (PFS) was determined in pts observed ≥1 year (recruited Results 94%/65% of 1732/472 pts with non-squamous/squamous tumors were tested for any biomarker. In 2018 test rate was 96%/75% and 49%/33% were tested for all biomarkers (EGFR, ALK, ROS1, BRAF) with approved targeted therapies (aTT). An alteration in EGFR, ALK, ROS1 or BRAF was detected in 9%, 3%, 2%, and 2% of pts, respectively. Details on the type of alteration will be presented. Of pts with druggable EGFR mutation (EGFR+ pts, n = 149) 78% received EGFR-aTT in 1st-line. In 2nd-line, 20% received EGFR-aTT, 15% something else, 11% died prior to 2nd-line, 54% were still in 1st-line. Median PFS of EGFR+ pts was 7.1 months (n = 67, 61% events, 95%-CI 5.2-10.1), in total 46% (n = 31) of pts had died (ous). Of pts with druggable ALK alteration (n = 55), 47% received ALK-aTT in 1st-line. In 2nd-line, 22% received ALK-aTT, 11% something else, 13% died prior to 2nd-line, 54% were still in 1st-line. In the ous (n = 29), 55% (n = 16) of tumors had already progressed, in total 24% (n = 7) of pts had died. All 6 pts with druggable ROS1 alteration received chemotherapy as 1st-line, while 6 of the 9 pts with druggable BRAF mutation and start of treatment in 2017/18 received a BRAF-ATT in 1st-line. Conclusions CRISP presents current real life data from Germany. Pts are frequently tested for molecular alterations. While EGFR-aTT is well established as 1st-line and first data are promising for BRAF-aTT, pts with ALK/ROS alteration do not seem to be routinely treated with 1st-line aTT, reasons are not yet clear and will be further evaluated. Outcome of pts will be further analyzed after longer follow-up. Clinical trial identification NCT02622581. Legal entity responsible for the study AIO-Studien-gGmbH. Funding AstraZeneca GmbH, Boehringer Ingelheim Pharma GmbH & Co. KG, Bristol-Myers Squibb GmbH & Co. KGaA, Celgene GmbH, MSD Sharp & Dohme GmbH, Lilly Deutschland GmbH, Novartis Pharma GmbH, Pfizer Pharma GmbH, Roche Pharma AG, and Takeda Pharma Vertriebs GmbH & Co. KG. Disclosure F. Griesinger: Honoraria (institution), Advisory / Consultancy: Ariad; Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution): Boehringer Ingelheim; Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution): Bristol-Myer-Squibb; Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution): Celgene; Honoraria (institution), Advisory / Consultancy: Clovis; Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution): Lilly; Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution): Merck-Sharp-Dome; Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution): Novartis; Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution): Pfizer; Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution): Roche. N.W. Marschner: Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Celgene; Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Lilly; Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution): MSD Sharp & Dohme; Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Novartis; Research grant / Funding (institution), Travel / Accommodation / Expenses: Pfizer; Leadership role, Shareholder / Stockholder / Stock options, Officer / Board of Directors: iOMEDICO. M. Janicke: Leadership role, Full / Part-time employment: iOMEDICO. A. Fleitz: Full / Part-time employment: iOMEDICO. L. Spring: Full / Part-time employment: iOMEDICO. J. Sahlmann: Leadership role, Full / Part-time employment: iOMEDICO. A. Karatas: Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Boehringer Ingelheim; Research grant / Funding (institution): Bristol-Myers Squibb; Research grant / Funding (institution): Celgene; Research grant / Funding (institution): MSD Sharp & Dohme; Research grant / Funding (institution): Lilly; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Takeda; Research grant / Funding (institution): Roche. A. Hipper: Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Boehringer Ingelheim; Research grant / Funding (institution): Bristol-Myers Squibb; Research grant / Funding (institution): Celgene; Research grant / Funding (institution): MSD Sharp & Dohme; Research grant / Funding (institution): Lilly; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Takeda; Research grant / Funding (institution): Roche. M. Sebastian: Advisory / Consultancy: Bristol-Myers Squibb; Advisory / Consultancy: MSD Sharp & Dohme; Advisory / Consultancy: Roche; Advisory / Consultancy: Novartis; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Boehringer Ingelheim Pharma; Advisory / Consultancy: Celgene; Advisory / Consultancy: Lilly; Advisory / Consultancy: Pfizer. M. Thomas: Honoraria (institution), Advisory / Consultancy: MSD Sharp & Dohme; Honoraria (institution), Advisory / Consultancy: Bristol-Myers Squibb; Honoraria (institution), Advisory / Consultancy: Lilly; Honoraria (institution), Advisory / Consultancy: AstraZeneca; Honoraria (institution), Advisory / Consultancy: Roche; Honoraria (institution), Advisory / Consultancy: Pfizer; Honoraria (institution), Advisory / Consultancy: Celgene; Honoraria (institution), Advisory / Consultancy: Novartis. All other authors have declared no conflicts of interest.

Background Treatment guidelines for metastatic non-small cell lung cancer recommend stratified treatment according to biomarker testing results. Here we used CRISP to evaluate treatment and outcome of patients (pts) with PD-L1-expressing tumors. Methods Currently 163 centers in Germany have recruited over 3700 pts at start of 1st-line who will be followed until death or end of project. Data from 2204 pts recruited by 133 centers between 12/2015 and 06/ 2018 was analyzed regarding PD-L1 testing, treatment and outcome. Progression-free survival (PFS) was determined in patients being ≥1 year under observation (recruited until June 30th 2017 (n = 906), outcome sample, (ous)). Results Test rates for PD-L1 increased from 25% (2016) to 75% (2018) in pts with non-squamous tumors (n = 1732), and from 20% (2016) to 62% (2018) in pts with squamous tumors (n = 472). Of pts with test results (n = 1221) PD-L1 antibodies mostly used were Ventana SP263 (19%), DAKO 28-8 or 22-C (8% each) or not known to the documenting site (56%). PD-L1 TPS was ≥50% in 16% of pts, 1-49% in 18% of pts, and Conclusions CRISP presents current real life data from Germany. Testing for PD-L1 has been quickly integrated into routine care diagnostics. The majority of pts with PD-L1 positive tumors and a TPS≥50% receive an immune-oncology therapy. The impact of these novel targeted treatment approaches on the outcome of pts will be subject of future analyses. Clinical trial identification NCT02622581. Legal entity responsible for the study AIO-Studien-gGmbH. Funding AstraZeneca GmbH, Boehringer Ingelheim Pharma GmbH & Co. KG, Bristol-Myers Squibb GmbH & Co. KGaA, Celgene GmbH, MSD Sharp & Dohme GmbH, Lilly Deutschland GmbH, Novartis Pharma GmbH, Pfizer Pharma GmbH, Roche Pharma AG, and Takeda Pharma Vertriebs GmbH & Co. KG. Disclosure M. Sebastian: Advisory / Consultancy: Bristol-Myers Squibb; Advisory / Consultancy: MSD Sharp & Dohme; Advisory / Consultancy: Roche; Advisory / Consultancy: Novartis; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Boehringer Ingelheim Pharma; Advisory / Consultancy: Celgene; Advisory / Consultancy: Lilly; Advisory / Consultancy: Pfizer. N.W. Marschner: Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Celgene; Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Lilly; Advisory / Consultancy, Research grant / Funding (institution): MSD Sharp & Dohme; Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Novartis; Research grant / Funding (institution), Travel / Accommodation / Expenses: Pfizer; Leadership role, Shareholder / Stockholder / Stock options, Officer / Board of Directors: iOMEDICO. M. Janicke: Leadership role, Full / Part-time employment: iOMEDICO. A. Fleitz: Full / Part-time employment: iOMEDICO. L. Spring: Full / Part-time employment: iOMEDICO. J. Sahlmann: Leadership role, Full / Part-time employment: iOMEDICO. A. Karatas: Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Boehringer Ingelheim; Research grant / Funding (institution): Bristol-Myers Squibb; Research grant / Funding (institution): Celgene; Research grant / Funding (institution): MSD Sharp & Dohme; Research grant / Funding (institution): Lilly; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Roche; Research grant / Funding (institution): Takeda. A. Hipper: Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Boehringer Ingelheim; Research grant / Funding (institution): Bristol-Myers Squibb; Research grant / Funding (institution): Celgene; Research grant / Funding (institution): MSD Sharp & Dohme; Research grant / Funding (institution): Lilly; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Roche; Research grant / Funding (institution): Takeda. F. Griesinger: Honoraria (institution), Advisory / Consultancy: Ariad; Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution): Boehringer Ingelheim; Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution): Bristol-Myer-Squibb; Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution): Celgene; Honoraria (institution), Advisory / Consultancy: Clovis; Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution): Lilly; Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution): Merck-Sharp-Dome; Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution): Novartis; Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution): Pfizer; Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution): Roche. M. Thomas: Advisory / Consultancy: MSD Sharp & Dohme; Advisory / Consultancy: Bristol-Myers Squibb; Advisory / Consultancy: Lilly; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Roche; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Celgene; Advisory / Consultancy: Novartis. All other authors have declared no conflicts of interest.

Health registries could be used to analyze questions concerning routine practice in healthcare. Therefore, registries are a core method in health services research. The German Network for Health Services Research (Deutsches Netzwerk Versorgungsforschung, DNVF) promotes the quality of registries by scientific exchange, organization of advanced training, and recommendations in the form of a memorandum "Registry for Health Services Research". The current recommendations are an update of the memorandum's first version of 2010. The update describes the capabilities and aims of registries in health services research. Furthermore, it illustrates the state-of-the-art in designing and implementing health registries. The memorandum provides developers the methodological basis to ensure high quality health registries. It further provides users of health registries with insights that enable assessing the quality of data and results of health registries. Finally, funding agencies and health policy actors can use the quality criteria to establish a framework for the financing and legislative requirements for health registries. The memorandum provides first a definition of health registries and presents an overview of their utility in health services research and health care improvement. Second, several areas of methodological importance for the development and operation of health registries are presented. This includes the conceptual and preliminary design, implementation, technical organization of a health registry, statistical analysis, reporting of results, and data protection. From these areas, criteria are deduced to allow the assessment of the quality of a health registry. Finally, a checklist is presented.Über Register können Fragestellungen zur Gesundheitsversorgung im Alltag untersucht werden. Sie sind daher eine wesentliche Methode der Versorgungsforschung. Das Deutsche Netzwerk Versorgungsforschung (DNVF) fördert die Qualität von Registern durch einen wissenschaftlichen Austausch, durch Fortbildungsangebote sowie durch Empfehlungen in Form eines Memorandums „Register für die Versorgungsforschung“. Die vorliegenden Empfehlungen stellen ein Update zur ersten Fassung des Memorandums von 2010 dar. Das Update beschreibt die Einsatzmöglichkeiten und Zielsetzungen von Registern in der Versorgungsforschung und stellt den aktuellen Stand zu allen Aspekten eines guten Designs und eines sachgerechten Betriebs von Registern dar. Das Memorandum kann Verantwortlichen für die Entwicklung eines Registers als Leitfaden zur Erreichung einer hohen Qualität dienen; potentiellen Nutzern von Daten und Ergebnissen aus Registern ermöglicht es, die Qualität eines Registers zu bewerten. Projektförderer und Gesundheitspolitik können sich bei der Rahmensetzung für Finanzierung und gesetzliche Anforderungen an den Qualitätskriterien orientieren. Neben einer Definition werden im Memorandum verschiedene für die Konzeption eines Registers relevante Bereiche vorgestellt. Dies umfasst die Phasen der Entwicklung eines Registers von der Planung über den Entwurf bis zur Umsetzung, die technische Organisation und den Betrieb eines Registers, die Auswertung von Registerdaten, die Berichterstattung über die Ergebnisse sowie den Datenschutz. Aus diesen Bereichen abgeleitete Kriterien zur Beurteilung der Qualität eines Registers werden beschrieben. Hierfür wird abschließend eine Checkliste präsentiert.

Pancreatic cancer is a highly lethal malignancy. Developments in recent years have broadened our therapeutic armamentarium. Novel drugs such as nab-paclitaxel, liposomal irinotecan and chemotherapy regimens such as FOLFIRINOX have been successfully tested in clinical trials. Data on patients outside of clinical trials are scarce but necessary to assess and improve the standard of care. We present data on treatment and survival of 1,174 patients with locally advanced, inoperable, or metastatic pancreatic ductal adenocarcinoma. Between February 2014 and June 2017, patients were recruited by 104 sites at start of first-line therapy into the ongoing, prospective clinical cohort study TPK (Tumour Registry Pancreatic Cancer). As first-line therapy, 89% of patients received one of the three treatment regimens: gemcitabine monotherapy (23%), nab-paclitaxel plus gemcitabine (42%), or FOLFIRINOX (24%). The corresponding subgroups differed: Patients receiving gemcitabine monotherapy were older and more comorbid (median age 78 years, 73% ECOG ≥ 1) than patients receiving nab-paclitaxel plus gemcitabine (median age 71, 64% ECOG ≥ 1) or patients receiving FOLFIRINOX (median age 60, 52% ECOG ≥ 1). At least 40% of patients died before receiving second-line treatment. First-line progression-free survival was 4.6 months (95% CI: 3.7-5.2) for gemcitabine, 5.6 months (95% CI: 5.0-6.2) for nab-paclitaxel plus gemcitabine, and 6.3 months (95% CI: 5.5-6.9) for FOLFIRINOX. Our data represent the treatment reality in a German community setting. Although there are no stringent inclusion criteria for our cohort study, overall survival is comparable to that reported by randomised clinical trials.

Despite increasing treatment options, multiple myeloma (MM) remains incurable for most patients. Data on improvement of outcomes are derived from selected patient populations enrolled in clinical trials and might not be conferrable to all patients. Therefore, we assessed the trial eligibility, sequential treatment, and survival of non-transplant patients with MM treated in German routine care. The prospective clinical cohort study TLN (Tumour Registry Lymphatic Neoplasms) recruited 285 non-transplant patients with symptomatic MM at start of first-line treatment in 84 centres from 2009 to 2011. Demographic and clinical data were collected until August 2016. Trial-ineligibility was determined by presence of at least one of the common exclusion criteria: heart/renal failure, liver/renal diseases, polyneuropathy, HIV positivity. All other patients were considered potentially trial-eligible. Thirty percent of the patients in our study were classified as trial-ineligible. Median first-line progression-free survival (PFS) and overall survival (OS) of trial-ineligible patients were inferior to that of potentially trial-eligible patients: PFS 16.2 months (95% CI (confidence interval) 11.1–20.4) vs. 27.3 months (95% CI 23.3–33.0); OS 34.2 months (95% CI 21.6–48.1) vs. 58.6 months (95% CI 48.6–64.4). A high percentage of non-transplant patients with MM in German routine care would be ineligible for participation in clinical trials. Despite similar treatment algorithms, their first-line PFS and OS were shorter than those of potentially trial-eligible patients; the survival data of the latter were similar to results from clinical trials. Physicians should be aware of the fact that results from clinical trials may not mirror “real world” patient outcomes when discussing outcome expectations with patients. Trial registration: Clinicaltrials.gov identifier: NCT00889798.

Korrektur zu 10.1016/j.lungcan.2020.10.012

Background Several regimens for which efficacy was established in randomized controlled trials are recommended in current treatment guidelines for early breast cancer. However, knowledge on use and effectiveness of commonly administered chemotherapeutic agents in real-life care and across all breast cancer subtypes is limited. Methods The prospective, multicentre German TMK cohort study (Tumour Registry Breast Cancer) recruited patients in 148 oncology outpatient-centres. Data from 1650 patients who completed adjuvant chemotherapy were analysed regarding treatment regimens and taxane use from 2007 to 2014. The association of patient characteristics with application of taxane-free regimens was examined with a multivariate regression model. Results The preferred adjuvant treatment shifted from fluorouracil, anthracycline and cyclophosphamide containing regimens to anthracycline/taxane combinations. Taxane use increased for all subtypes, and the greatest rise was among node-negative patients. Older age, node-negativity, lower grading, HR-positive/HER2-negative subtype and earlier start year of therapy were significantly associated with taxane-free therapy. Conclusions Treatment with anthracycline/taxane-based chemotherapy in Germany has been rising for every subtype. The increased taxane use reflects updated guideline recommendations over the past decade. Cohort studies like the TMK provide insight into real-life treatment of patients outside of clinical trials. Electronic supplementary material The online version of this article (10.1007/s12282-017-0823-7) contains supplementary material, which is available to authorized users.

Purpose There is an ongoing discussion about ‘undertreatment’ of breast cancer in elderly patients. Due to low accrual into clinical trials, level 1 evidence is scarce. We report prospective data of elderly patients with breast cancer treated by medical oncologists in Germany. Methods The SENORA project within the prospective cohort study TMK (Tumour Registry Breast Cancer) was conducted in 82 centres from 2007–2015. Among 2316 patients, half were enrolled with curative and half with palliative treatment intention. Overall, 478 patients (21%) were aged ≥ 70. Results In the adjuvant setting, elderly patients aged ≥ 70 had more advanced tumour stages at diagnosis and a higher prevalence of comorbidities than younger patients. Elderly patients received adjuvant chemotherapy less frequently, yet the 3-year disease-free survival was similar (86% vs. 88%). In the palliative setting, elderly patients more frequently received endocrine therapy and less frequently chemotherapy. Their median overall survival [24.9 months, 95% CI (confidence interval) 20.0–30.2] was significantly shorter than that of younger patients (39.7 months, 95% CI 34.9–44.2). A Cox proportional hazards model showed a significantly increased risk of mortality for: age ≥ 70 at start of therapy, negative HR- or HER2-status, higher number of metastatic sites, more comorbidities and high tumour grading at diagnosis. Conclusions Our results shed light on the routine treatment of elderly patients with breast cancer. A regression model demonstrated that age is but one of various prognostic factors determining the shorter overall survival of elderly patients.

Purpose Although treatment for early breast cancer improved prognosis greatly, it can have significant long-term consequences, which must be considered during treatment decision. Methods 453 patients with neoadjuvant or adjuvant treatment intention were recruited into the MaTox project within the prospective, multicentre, population-based German TMK cohort study (Tumour Registry Breast Cancer) between 2008 and 2009. Patient-reported outcomes (PROs) on 26 treatment-related symptoms were assessed via a specifically designed questionnaire at 4 weeks, 6 months, 18 months and 3 years after start of systemic treatment. Results The results show that alterations in smell, taste and appetite were clearly improved 3 years after treatment. In contrast, post-surgical symptoms, restrictions in memory/attention, musculoskeletal system and polyneuropathy worsened substantially over time and were persistent after 3 years: 78% of the patients recorded impairment in memory, 73% muscle pain, 67% pain at the operated site and 57% paraesthesia in fingers or toes. A logistic regression model showed that risk factors for developing persistent paraesthesia symptoms were age, early paraesthesia symptoms and taxane-based therapy. Conclusions Our data show that most patients with breast cancer have persistent impairments negatively influencing their daily life even 3 years after treatment. Furthermore, we highlight areas requiring special attention in follow-up care. Electronic supplementary material The online version of this article (doi:10.1007/s10549-017-4365-7) contains supplementary material, which is available to authorized users.

IntroductionBecause “real-life” patients often do not meet the strict eligibility criteria of clinical trials, we assessed the trial eligibility of patients with advanced or metastatic renal cell carcinoma (mRCC) in routine practice and compared the survival of “trial-ineligible” and potentially “trial-eligible” patients.Patients and MethodsThe present prospective, multicenter German cohort study is recruiting patients from 110 oncology/urology outpatient centers and hospitals at initiation of systemic first-line treatment. The demographic, clinical, treatment, and survival data were collected. We defined patients as “trial-ineligible” when ≥ 1 exclusion criterion (Karnofsky performance status < 80%, hemoglobin less than the lower limit of normal, non–clear cell carcinoma histology) was documented. Otherwise, the patients were considered “trial-eligible”.ResultsOf 732 patients included, 57% were classified as “trial-ineligible”. Overall, the median first-line progression-free survival (PFS) was 7.9 months (95% confidence interval [CI], 6.9-8.9 months). The median first-line PFS of “trial-eligible” and “trial-ineligible” patients was 11.0 months (95% CI, 9.6-13.1 months) and 5.3 months (95% CI, 4.6-6.5 months), respectively. The median OS of the “trial-eligible” and “trial-ineligible” patients was 26.0 months (95% CI, 22.1-29.7 months) and 12.6 months (95% CI, 10.6-15.8 months), respectively.ConclusionOur data suggest that patients in routine practice differ from patients treated in clinical trials and that almost 60% of mRCC patients in German routine practice would be ineligible for participation in clinical trials. While their first-line PFS and OS were shorter than those of “trial-eligible” patients, the PFS and OS of “trial-eligible” patients were comparable with the results from clinical trials. Physicians should be aware of these differences when discussing treatment options and outcome expectations with patients.

OBJECTIVES R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) is the standard therapy for patients with previously untreated diffuse large B-cell lymphomas (DLBCL). Dose-dense two-weekly 'R-CHOP-14' was not superior over three-weekly 'R-CHOP-21' in randomised clinical trials (RCTs). We present real-world data on effectiveness of R-CHOP-14 and R-CHOP-21 in patients with DLBCL treated in German routine practice. METHODS We identified 582 patients with DLBCL treated with R-CHOP-14 or R-CHOP-21 in 92 sites from the prospective clinical cohort study Tumour Registry Lymphatic Neoplasms. Patients' schedules were classified by (a) length of the initial first cycle and (b) length of cycles 1-4. RESULTS About 55% of patients received R-CHOP-21, 45% R-CHOP-14, in median 6 cycles. 51% and 55% of patients, respectively, were able to continue their initial R-CHOP-14 and R-CHOP-21 schedule. While most characteristics between the patient cohorts were similar, patients receiving R-CHOP-21 presented slightly more often with tumour stage I and lower IPI risk. 3-year overall survival of patients with R-CHOP-14 and R-CHOP-21 did not differ: 84% vs 84% (first cycle), 87% vs 89% (cycles 1-4). CONCLUSIONS Patients with DLBCL in Germany are slightly more likely to receive R-CHOP-21 than R-CHOP-14. Both schedules are similarly effective in routine practice confirming the results from RCTs.

Importance: Mortality, morbidity, and health-related quality of life (HRQoL) are patient-relevant end points generally considered in the early benefit assessments of new cancer treatments. Progression-related end points, such as time to progression or progression-free survival, are not included, although patients and physicians testify to the detrimental association of disease progression with HRQoL. Objective: To examine the association of disease progression and HRQoL in 4 prevalent solid-cancer entities in routine clinical practice. Design, Setting, and Participants: This cohort study evaluated data from 4 prospective, nonintervention, multicenter registries collected between 2011 and 2018 in 203 centers in Germany. Patients' HRQoL was assessed regularly for up to 5 years. The change in HRQoL scores after disease progression was examined with linear mixed models, adjusting for demographic and clinical covariates. Patients with metastatic breast, pancreatic, lung, and colorectal cancer were recruited at the start of systemic first-line treatment. Data analysis was performed from February 2019 to April 2019. Exposures: All patients received systemic, palliative first-line treatment according to their physician's choice. Main Outcomes and Measures: The primary outcome was deterioration of HRQoL associated with disease progression, as measured by 4 validated questionnaires: Functional Assessment of Cancer Therapy-General version 4, European Organization for Research and Treatment of Cancer QLQ-C30 version 3.0, European Organization for Research and Treatment of Cancer QLQ-C15-PAL version 1, and Hospital Anxiety and Depression Scale. Results: More than 8000 questionnaires from 2314 patients with 2562 documented disease progressions were analyzed. In total, 464 patients had breast cancer (464 [100.0%] female; median [range] age, 61.6 [26.4-90.1] years), 807 patients had pancreatic cancer (352 [43.6%] female; median [range] age, 70.0 [39.0-93.0] years), 341 patients had lung cancer (118 [34.6%] female; median [range] age, 65.9 [28.4-88.2] years), and 702 patients had colorectal cancer (248 [35.3%] female; median [range] age, 66.9 [26.9-92.1] years). The first disease progression was associated with a statistically significant worsening of 37 of 45 HRQoL scales; for 17 of these scales, the worsening was clinically meaningful. Scale scores for appetite loss (pancreatic cancer, 10.2 points [95% CI, 6.8-13.5 points]; lung cancer, 10.8 points [95% CI, 5.4-16.2 points]; colorectal cancer, 8.8 points [95% CI, 5.5-12.2]; all P

Introduction Because the treatment landscape for metastatic renal cell carcinoma (mRCC) has evolved dramatically over the past decade, data on patients' treatment and outcomes in routine practice, so called “real-world data,” are important to complement clinical trial data. We present choice of systemic first-/second-line treatments, number and sequences of treatment lines, and survival of patients with clear cell mRCC. Patients and Methods A total of 1085 patients with clear cell mRCC who were recruited at the start of first-line treatment into the prospective German clinical cohort study (RCC-Registry) by 122 sites between December 2007 and May 2017 were analyzed. Results The choice of first-/second-line treatment and changes over time reflect the chronologic approval of different targeted agents: from mainly tyrosine kinase inhibitors (TKIs), to TKIs/mechanistic target of rapamycin inhibitors, to now TKIs/mechanistic target of rapamycin inhibitors/checkpoint inhibitor. The median first-line overall survival ranged from 7.2 months (95% confidence interval [CI], 4.8-10.9 months) in high MSKCC (Memorial Sloan Kettering Cancer Center) risk to 36.7 months (95% CI, 27.9-43.0 months) in low-risk patients. For trial-ineligible routine patients meeting common exclusion criteria of clinical trials, the median overall survival was 14.6 months (95% CI, 11.5-18.0 months) compared with 26.2 months (95% CI, 22.1-31.5 months) for potentially trial-eligible patients. Conclusion This is the first prospective long-term cohort study showing changes in treatment reality and survival of routine patients with clear cell mRCC. Newly approved treatments are quickly applied in routine care. Patients with unfavorable prognosis, including trial-ineligible patients, have inferior outcomes. Survival times of potentially trial-eligible patients are similar to those reported from clinical trials.

Pancreatic cancer is a highly lethal malignancy. Developments in recent years have broadened our therapeutic armamentarium. Novel drugs such as nab‐paclitaxel, liposomal irinotecan and chemotherapy regimens such as FOLFIRINOX have been successfully tested in clinical trials. Data on patients outside of clinical trials are scarce but necessary to assess and improve the standard of care. We present data on treatment and survival of 1,174 patients with locally advanced, inoperable, or metastatic pancreatic ductal adenocarcinoma. Between February 2014 and June 2017, patients were recruited by 104 sites at start of first‐line therapy into the ongoing, prospective clinical cohort study TPK (Tumour Registry Pancreatic Cancer). As first‐line therapy, 89% of patients received one of the three treatment regimens: gemcitabine monotherapy (23%), nab‐paclitaxel plus gemcitabine (42%), or FOLFIRINOX (24%). The corresponding subgroups differed: Patients receiving gemcitabine monotherapy were older and more comorbid (median age 78 years, 73% ECOG ≥ 1) than patients receiving nab‐paclitaxel plus gemcitabine (median age 71, 64% ECOG ≥ 1) or patients receiving FOLFIRINOX (median age 60, 52% ECOG ≥ 1). At least 40% of patients died before receiving second‐line treatment. First‐line progression‐free survival was 4.6 months (95% CI: 3.7–5.2) for gemcitabine, 5.6 months (95% CI: 5.0–6.2) for nab‐paclitaxel plus gemcitabine, and 6.3 months (95% CI: 5.5–6.9) for FOLFIRINOX. Our data represent the treatment reality in a German community setting. Although there are no stringent inclusion criteria for our cohort study, overall survival is comparable to that reported by randomised clinical trials., What's new? More than four‐fifths of patients with pancreatic cancer present with locally advanced, inoperable (LAPC) or metastatic (MPC) disease at diagnosis. Beyond clinical trials, relatively little data is available on survival outcomes for these patients. Here, real‐world data, derived from an unselected cohort of 1,174 patients enrolled between 2014 and 2017 in a prospective study in Germany, show that the vast majority of first‐line therapies given to LAPC/MPC patients consisted of either gemcitabine monotherapy, nab‐paclitaxel plus gemcitabine, or FOLFIRINOX. About 40 percent of the patients received second‐line therapy. Overall cohort survival was comparable to that reported for randomized clinical trials.

e21236Background: Treatment in non-small cell lung cancer is quickly evolving and new agents make it to the routine practice at a rapid pace. It is of high interest to patients (pts), physicians an...

Objectives Real-life data on advanced non-small cell lung cancer (NSCLC) are centrally important to complement the results from clinical trials and to improve the standard of care. We present data on the choice of systemic first- and second-line treatment, number of treatment lines, survival and longitudinal data on health-related quality of life (HRQOL) of patients treated by medical oncologists in Germany. Materials and methods 1239 patients with advanced NSCLC were recruited at start of first-line therapy into the prospective German clinical cohort study TLK (Tumour Registry Lung Cancer) by 107 sites between February 2010 and December 2013 and followed-up until January 2016. HRQOL was assessed using the EORTC QLQ-C30 and LC13 questionnaires. Results Most patients receive carboplatin- or cisplatin-based doublet chemotherapy in first-line treatment. The choice of platinum agent did neither influence the outcome: median overall survival (OS) was 12.2 months for carboplatin combinations (95% confidence interval [CI] 10.0–13.8) and 11.9 months for cisplatin combinations (95% CI 10.2–13.8), nor did it have a marked impact on the HRQOL. Patients receiving cisplatin were younger and fitter at start of therapy than patients receiving carboplatin or mono-chemotherapy. The longitudinal HRQOL analysis revealed the main symptoms that need to be addressed in follow-up care, irrespective of the platinum agent: fatigue, nausea, dyspnoea and pain. The patients receiving targeted therapies with tyrosine kinase inhibitors (TKIs) had a median OS of 22.1 months (95% CI 15.0–35.1) and considerably superior HRQOL. Conclusion There was no difference in outcome between the platinum compounds cisplatin and carboplatin in first-line treatment of advanced NSCLC in routine care. This is the first report of longitudinal HRQOL data comparing treatments, showing no difference between carboplatin and cisplatin.

A high proportion of patients with breast cancer develop bone metastases, yet data on routine treatment with bone-targeted agents (BTA) are rare. We report real-life outcome data of patients with breast cancer metastasised to the bone treated by office-based oncologists in Germany. The ongoing, prospective, multicentre, population-based cohort study Tumour Registry Breast Cancer (TMK) was started in 2007 in 140 centres across Germany. This interim analysis of 1094 patients with bone metastases revealed differences among the tumour subtypes: at start of first-line therapy, 36% of the patients with hormone receptor (HR)-positive and only 20% of the patients with HR-negative tumours presented with bone-only metastasis. The majority of patients with bone metastases (89%, n = 976) received BTA therapy. In 2014–2015, 37% of the patients received the bisphosphonate zoledronic acid and 36% the antibody denosumab. Median duration of BTA therapy was 20 months (interquartile range 31.5 months), starting a median of 3 weeks after diagnosis of bone metastases, and ending a median of 7 weeks before death. The median overall survival (OS) also varied among the types of metastasis at start of first-line therapy ranging from 54 months (95% confidence interval [CI] 37.6–70.8), 38 months (95% CI 29.4–44.2) to 28 months (95% CI 24.2–31.0) for patients with bone-only metastases, non-visceral with or without bone metastases and visceral with or without bone metastases respectively. We show that choice and duration of BTA therapies are in conformity with guidelines applicable in Germany. To our knowledge, this is the first presentation of data on incidence, metastatic pattern, treatment and survival of patients with bone metastases in routine practice.

Background For patients (pts) with advanced or metastatic renal cell carcinoma (mRCC), approval of novel therapies led to continuous changes in treatment options. The Tumour Registry Renal Cell Carcinoma (TNK) analysed treatment and outcome of pts treated in Germany from 2007-2017. CARAT is the successor registry, which continues to assess longitudinal real world clinical outcome, incl. patient-reported outcomes (PROs) and decentralized biobanking. Today, we introduce CARAT and report on current changes of the treatment landscape in mRCC in Germany. Methods Since Dec 2017 150 pts have been enrolled in CARAT, expanding the previous TNK (2007-17, 1500 pts). CARAT is an observational, prospective, open, multicentre clinical research platform aiming to enrol 1000 pts by 150 sites. Pts with mRCC who start systemic 1stline treatment are eligible. Treatment characteristics, clinical outcome and physician-reported factors on treatment decision making are collected. Overall survival (OS) is assessed by the KM-method. Changes of the treatment landscape are shown descriptively. Results By April 2019 >1650 pts with mRCC have been recruited. Median age is 68 years. 60% had intermediate risk (MSKCC) at start of 1st-line. Median OS for pts with start of 1st-line 2007-17 is 19 months (>60% events). If selected by trial eligibility criteria, the median OS is 27 months. Pts who started treatment in 2018 mostly received pazopanib or sunitinib (38%/34%). Since the approval (May 2018) 18% are treated with cabozantinib. Preferred 2nd-line treatment changed from sorafenib/temsirolimus (35%/21%, 2007-09), everolimus (33% 2010-12), everolimus/axitinib/sunitinib (29%/19%/18%, 2013-15) to nivolumab (>60% since 2016). The impact of new treatment options on OS will be analysed. Conclusions Pts in routine care in Germany are older and have inferior prognosis than trial-eligible pts. CARAT complements results of RCTs with prospective data on clinical and PROs for pts with mRCC in routine care. CARAT will show changes in the choice of treatment due to new approvals, applied sequences and investigate the effectiveness in a “real world” setting. For the first time, these data will be combined with PROs and a decentralized biobank for translational research. Legal entity responsible for the study IOMEDICO. Funding Ipsen. Disclosure P.J. Goebell: Honoraria (self), Advisory / Consultancy: Amgen; Honoraria (self), Advisory / Consultancy: Astellas; Honoraria (self), Advisory / Consultancy: AstraZeneca; Honoraria (self), Advisory / Consultancy: Bayer; Honoraria (self), Advisory / Consultancy: BMS; Honoraria (self), Advisory / Consultancy: Eisai; Honoraria (self), Advisory / Consultancy: Ipsen; Honoraria (self), Advisory / Consultancy: Janssen; Honoraria (self), Advisory / Consultancy: MSD; Honoraria (self), Advisory / Consultancy: Novartis; Honoraria (self), Advisory / Consultancy: Pfizer; Honoraria (self), Advisory / Consultancy: Sanofi; Honoraria (self): IOMEDICO. M. Bogemann: Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): Janssen; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): Astellas; Honoraria (self), Advisory / Consultancy: Novartis; Honoraria (self), Advisory / Consultancy: Pfizer; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): Ipsen; Honoraria (self), Advisory / Consultancy: BMS; Honoraria (self), Advisory / Consultancy: MSD; Honoraria (self), Advisory / Consultancy: Eisai; Honoraria (self), Advisory / Consultancy: Bayer; Honoraria (self), Advisory / Consultancy: Eusa Pharma; Honoraria (self), Advisory / Consultancy: ABX; Honoraria (self), Advisory / Consultancy: Sanofi; Honoraria (self), Advisory / Consultancy: AstraZeneca; Honoraria (self), Advisory / Consultancy: Amgen. S. Dorfel: Shareholder / Stockholder / Stock options: IOMEDICO. N.W. Marschner: Advisory / Consultancy, Leadership role, Research grant / Funding (institution), Shareholder / Stockholder / Stock options: IOMEDICO; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Ipsen. M. Staehler: Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): Pfizer; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): Bayer; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): Novartis; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): GSK; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): Roche. V. Grunwald: Honoraria (self), Research grant / Funding (self), Shareholder / Stockholder / Stock options, Non-remunerated activity/ies: MSD; Research grant / Funding (self): Novartis; Honoraria (self), Research grant / Funding (self), Shareholder / Stockholder / Stock options: AstraZeneca; Honoraria (self), Research grant / Funding (self), Shareholder / Stockholder / Stock options, Non-remunerated activity/ies: BMS; Honoraria (self), Non-remunerated activity/ies: Merck Serono; Honoraria (self): Roche; Honoraria (self): Pfizer; Honoraria (self): Lilly; Honoraria (self), Non-remunerated activity/ies: PharmaMar; Honoraria (self): Nanobiotix; Honoraria (self): Janssen. All other authors have declared no conflicts of interest.

Data on treatment and outcome of advanced breast cancer in routine practice are rare, especially concerning recurrent disease, but important to complement the results from clinical trials and to improve the standard of care. We present data on choice of systemic first-line treatment, number of treatment lines, and survival of patients treated by medical oncologists in Germany. 1395 patients recruited by 124 sites at start of first-line therapy into the ongoing, prospective German clinical cohort study TMK (Tumour Registry Breast Cancer) between February 2007 and October 2015 were analysed. The median OS was 33.8 months (95% CI 30.2-40.2) for HR-positive/HER2-negative, 38.2 months (95% CI 31.3-43.0) for HER2-positive and 16.8 months (95% CI 11.5-22.0) for triple negative breast cancer. Patients with triple negative tumours more often died before start of a third-line therapy than patients with HR-positive or HER2-positive tumours (44% vs. 25%). Use of taxane-based chemotherapies has increased since 2007, with 65% of all first-line chemotherapy-treatments containing taxanes in 2013-15 (60% HR-positive/HER2-negative, 75% HER2-positive, 56% triple negative). 52% of the patients with HR-positive/HER2-negative tumours received first-line endocrine therapy in 2013-15; when restricted to patients with only non-visceral metastases this percentage increased to 63%. To our knowledge, this is the first cohort study showing systemic first-line therapy for all subtypes of advanced breast cancer. Overall survival in the TMK is comparable to that reported by clinical trials despite the inclusion of older and comorbid patients.

TPS9108Background: Treatment in NSCLC is quickly evolving. Whether outcome and PRO data generated in clinical trials with narrow inclusion and exclusion criteria will hold up in the routine practic...

Objectives A high body mass index (BMI) is associated with an increased risk for developing renal cell carcinoma (RCC), a higher complication rate after surgery, and a postoperative decline in renal function after nephrectomy. In contrast, a high preoperative BMI has been associated with increased survival in patients with localized RCC. We examined the prognostic impact of the BMI in patients treated for metastatic RCC (mRCC) in daily routine practice in Germany. Patients and Methods The ongoing prospective, multicenter German clinical cohort study on mRCC (RCC-Registry) has recruited patients from more than 110 oncology/urology outpatient centers and hospitals at initiation of systemic first-line treatment. Data on patients’ demographics, treatment, and outcome in routine practice, so called “real world data”, have been collected. For this analysis, 606 patients were stratified into a low (BMI 28) BMI group. The influence of the BMI on the overall survival (OS) was analyzed using a multivariate Cox proportional hazards model. Results Median OS was 24.5 (95% confidence interval [CI], 19.3–28.5), 17.9 (95% CI, 15.3–20.8) and 10.9 (95% CI, 7.3–13.4) months in the high, medium, and low BMI patient group, respectively. A significant correlation of BMI with OS, independent of other factors, was found (low vs. high BMI: hazard ratio (HR): 1.94, 95% CI, 1.48–2.54; medium vs. high BMI: HR: 1.40, 95% CI, 1.10–1.78). Memorial Sloan Kettering Cancer Center risk factors were independently correlated with shorter OS. Conclusions Our analysis showed a significant and independent correlation of a high BMI with longer OS in a prospective German cohort of mRCC routine patients starting first-line systemic treatment.

Grainyhead/CP2 transcription factor family members are widely conserved among the animal kingdom and have been implicated in different developmental processes. Thus far, nothing has been known about their roles in zebrafish. Here we identify seven zebrafish grainyhead-like (grhl) / cp2 genes, with focus on grhl1, which is expressed in the periderm and in epidermal ionocyte progenitors, but downregulated when ionocytes differentiate. In addition, expression was detected in other "non-keratinocyte" cell types of the epidermis, such as pvalb8-expressing cells, which according to our lineage tracing experiments are derived from the same pool of progenitor cells like keratinocytes and ionocytes. Antisense morpholino oligonucleotide-based loss-of-function analysis revealed that grhl1 is dispensable for the development and function of all investigated epidermal cell types, but required as a negative regulator of its own transcription during ionocyte differentiation. Knockdown of the transcription factor Foxi3a, which is expressed in a subset of the grhl1 population, caused a loss of ionocytes and a corresponding increase in the number of pvalb8-expressing cells, while leaving the number of grhl1-positive cells unaltered. We propose that grhl1 is a novel common marker of all or most "non-keratinocyte" epidermal progenitors, and that the sub-functionalisation of these cells is regulated by differential positive and negative effects of Foxi3 factors.

Skeletal syndromes are among the most common birth defects. Vertebrate skeletogenesis involves two major cell types: cartilage-forming chondrocytes and bone-forming osteoblasts. In vitro, both are under the control of retinoic acid (RA), but its exact in vivo effects remained elusive. Here, based on the positional cloning of the dolphin mutation, we have studied the role of the RA-oxidizing enzyme Cyp26b1 during cartilage and bone development in zebrafish. cyp26b1 is expressed in condensing chondrocytes as well as in osteoblasts and their precursors. cyp26b1 mutants and RA-treated wild-type fish display a reduction in midline cartilage and the hyperossification of facial and axial bones, leading to fusions of vertebral primordia, a defect not previously described in the context of RA signaling. Fusions of cervical vertebrae were also obtained by treating mouse fetuses with the specific Cyp26 inhibitor R115866. Together with data on the expression of osteoblast markers, our results indicate that temporal and spatial restriction of RA signaling by Cyp26 enzymes is required to attenuate osteoblast maturation and/or activity in vivo. cyp26b1 mutants may serve as a model to study the etiology of human vertebral disorders such as Klippel-Feil anomaly.

Ionocytes are specialized epithelial cell types involved in the maintenance of osmotic homeostasis. In amniotes, they are present in the renal system, while in water-living embryos of lower vertebrates additional ionocytes are found in the skin. Thus far, relatively little has been known about the mechanisms of ionocyte development. Here we demonstrate that skin ionocytes of zebrafish embryos derive from the same precursor cells as keratinocytes. Carrying out various combinations of gain- and loss-of-function studies, we show that the segregation of ionocytes from the epidermal epithelium is governed by an interplay between Notch signaling and two Forkhead-box transcription factors, Foxi3a and Foxi3b. The two foxi3 genes are expressed in ionocyte precursors and are required both for ionocyte-specific expression of the Notch ligand Jagged2a, and for ionocyte differentiation, characterized by the production of particular ATPases. Ionocytic Notch ligands, in turn, signal to neighboring cells, where activated Notch1 leads to a repression of foxi3 expression, allowing those cells to become keratinocytes. A model for ionocyte versus keratinocyte development will be presented, postulating additional thus far unidentified pro-ionocyte factors.

Norbert Marschner,1 Dirk Arnold,2 Erik Engel,3 Ulrich Hutzschenreuter,4 Jacqueline Rauh,5 Werner Freier,6 Holger Hartmann,7 Melanie Frank,8 Martina Jänicke7 On behalf of the TKK Registry Group 1Praxis für Interdisziplinäre Onkologie und Hämatologie, 2Klinik für Tumorbiologie, Freiburg, Germany; 3Hämatologisch – Onkologische Praxis Altona, Hamburg, Germany; 4Hämatologisch – Onkologische Gemeinschaftspraxis, Nordhorn, Germany; 5Fachinternistische Gemeinschaftspraxis und Therapiezentrum, Witten, Germany; 6Onkologische Praxis, Hildesheim, Germany; 7Clinical Epidemiology and Health Economics, iOMEDICO, 8Statistics, iOMEDICO, Freiburg, Germany Purpose: Several randomized trials investigating the preferable first-line combination chemotherapy regimen for metastatic colorectal cancer have shown inconsistent findings. Because a substantial number of patients are still being treated with "chemo-only" first-line therapies without targeted agents, we compared overall survival (OS) of patients treated in routine practice with oxaliplatin–fluoropyrimidine and irinotecan–fluoropyrimidine. Patients and methods: Using the database of the Tumor Registry Colorectal Cancer, we identified 605 patients with metastatic colorectal cancer who received first-line fluoropyrimidine combination chemotherapy with either oxaliplatin (n=430) or irinotecan (n=175). The Tumor Registry Colorectal Cancer is a cohort study that prospectively documents treatment of colorectal cancer by office-based medical oncologists in Germany and has recruited over 5,000 patients. OS was estimated using the Kaplan–Meier method, and a multivariate Cox proportional hazard model was used to adjust for potentially confounding variables. Results: Median OS was 26.8 (95% confidence interval [CI] 22.4–31.9) months with an oxaliplatin–fluoropyrimidine combination and 18.3 (95% CI 15.1–23.2) months with irinotecan–fluoropyrimidine first-line "chemo-only" therapy. Median progression-free survival was 9.0 (8.1–10.2) and 7.9 (7.2–10.2) months, respectively. The difference in OS was confirmed if analysis was restricted to patients with synchronous metastases (no prior treatment). Among other variables, proportion of patients receiving any second-line therapy did not differ between groups. Oxaliplatin-based first-line therapy was associated with improved OS in multivariate analysis adjusted for potentially confounding variables (hazard ratio 0.678, 95% CI 0.510–0.901, P=0.007). Conclusion: In clinical routine practice, first-line treatment with oxaliplatin–fluoropyrimidine combination chemotherapy compared to irinotecan–fluoropyrimidine combination is associated with improved survival in patients with metastatic colorectal cancer, independent of all examined potentially confounding factors. Keywords: colorectal neoplasms, epidemiology, irinotecan, oxaliplatin, cohort studies, treatment outcome