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Zusammenfassung Hintergrund COVID-19 betrifft im ambulanten Bereich vor allem auch Palliativpatienten, die im Rahmen der spezialisierten ambulanten Palliativversorgung (SAPV) versorgt werden. Zur Vermeidung von Infektionen wurde die Implementierung von neuen Sicherheitsvorkehrungen und telemedizinischen Kommunikationsmöglichkeiten in die an der Studie beteiligten SAPV erforderlich. Ziel der Arbeit Die Studie untersucht die Auswirkungen der COVID-19-Pandemie auf die persönlichen und sozialen Probleme von Palliativpatienten und ihre Erfahrungen mit der betreuenden SAPV. Material und Methoden 20 SAPV-Patienten wurden in halbstrukturierten Telefoninterviews zu ihren Problemen im Zusammenhang mit der Pandemie und Erfahrungen mit der SAPV-Betreuung befragt. Ergebnisse Angst vor Einsamkeit und Infektion belasten Palliativpatienten sehr. Die meisten Patienten wollten Krankenhausaufenthalte wegen erhöhter Infektionsgefahr vermeiden. Schutzmaßnahmen der SAPV gaben ihnen ein Gefühl der Sicherheit und wurden trotz Einschränkung des persönlichen Kontakts akzeptiert. Moderne Kommunikationsformen waren nützlich, konnten aber den persönlichen Kontakt nicht ersetzen. Diskussion Die Pandemie führte zu Veränderungen in der SAPV und hatte Auswirkungen auf das soziale Umfeld von Palliativpatienten. Schutzmaßnahmen sind für das Sicherheitsgefühl der betreuten Palliativpatienten wichtig. Die Versorgungsqualität der an COVID-19 angepassten SAPV-Struktur wird von den Patienten meist nicht als verschlechtert wahrgenommen. Ängste vor sozialer Isolation nehmen bei den Palliativpatienten einen hohen Stellenwert ein und können durch die SAPV abgebaut werden. Der persönliche Kontakt zur SAPV kann durch moderne Kommunikationsmöglichkeiten nicht ersetzt werden, wobei die Patienten Telemedizin im Sinne einer „Notlösung“ durchaus akzeptieren.

Observation is the current standard of care for patients with early-stage asymptomatic chronic lymphocytic leukemia (CLL), as chemotherapy-based interventions have failed to prolong survival. We hypothesized that early intervention with ibrutinib would be well tolerated and lead to superior disease control in a subgroup of early-stage patients with CLL. The phase 3, double-blind, placebo-controlled CLL12 trial randomly assigned asymptomatic, treatment-naïve Binet stage A CLL patients at increased risk of progression in a 1:1 ratio to receive ibrutinib (n = 182) or placebo (n = 181) at a dose of 420 mg daily. At a median follow-up of 31 months, the study met its primary endpoint by significantly improving event-free survival in the ibrutinib group (median, not reached vs 47.8 months; hazard ratio = 0.25; 95% confidence interval = 0.14-0.43, P < .0001). Compared with placebo, ibrutinib did not increase overall toxicity, yielding similar incidence and severity of adverse events (AEs). The most common serious AEs were atrial fibrillation, pneumonia, and rash in the ibrutinib group, and basal cell carcinoma, pneumonia, and myocardial infarction in the placebo group. Ibrutinib-associated risk for bleeding (33.5%) was decreased by prohibiting the use of oral anticoagulants through an amendment of the study protocol and by avoiding CYP3A4 drug–drug interactions. Ibrutinib confirms efficacy in CLL patients at an early stage with an increased risk of progression. However, the results do not justify changing the current standard of “watch and wait.” This trial was registered at www.clinicaltrials.gov as #NCT02863718.

Zusammenfassung Ziel der Studie Die Folgen der Covid-19-Pandemie (z. B. Schutzmaßnahmen, digitale Kommunikation) auf die Versorgungsrealität in der SAPV sollen aus Sicht von Mitarbeitern aus SAPV, Pflegeheimen und Hospizen untersucht werden. Methodik Insgesamt wurden jeweils 10 Mitarbeiter aus einer SAPV bzw. Leitungskräfte von Pflegeheimen/Hospiz mittels qualitativer Leitfadeninterviews befragt. Die Auswertung erfolgt mittels qualitativer Inhaltsanalyse nach Mayring. Ergebnisse Neue Schutzmaßnahmen waren für das SAPV-Team sehr bedeutsam. In der SAPV treten Belastungen v. a. durch Abstandsregelungen und erhöhte Arbeitsbelastungen auf. Zu digitalen Kommunikationsformen äußerte sich die Mehrzahl der Befragten positiv, persönlicher Kontakt (zu Patienten/zwischen Fachpersonal) bleibt wichtig. Schlussfolgerung Schutzmaßnahmen führen im Bereich Patientenversorgung und im Team zur Mehrbelastung, vermitteln aber Sicherheit und tragen zur Stressreduktion bei. COVID-19 kann zur Diagnoseverschiebung in der SAPV und zur engeren Zusammenarbeit mit Hausärzten führen.

Zusammenfassung Ziel der Studie Tageshospize stellen einen neuen Baustein der palliativmedizinischen Versorgung dar. Daten zu organisatorischen und grundlegenden versorgungsrelevanten Aspekten liegen kaum vor. Diese sollen nun aus Sicht von Patienten und Angehörigen erhoben werden. Methodik In einer schriftlichen Umfrage unter 209 Palliativpatienten und 105 Angehörigen an drei onkologischen Zentren wurden erste Eindrücke zum Bedarf und zur Planungsumsetzung von Tageshospizen ermittelt. Ergebnisse 81 % (n = 169) der Patienten und 75 % (n = 79) der Angehörigen erwarteten einen Benefit durch den Besuch von Tageshospizen. Öffnungszeiten wurden v. a. wochentags von 7:00–19:00 Uhr präferiert. 39 % (n = 41) der Angehörigen fühlten sich durch die Patientenpflege zeitweise überlastet, 80 % (n = 84) gingen von einer Entlastung durch ein Tageshospiz aus. Schlussfolgerung Tageshospize könnten aus Sicht von Patienten und Angehörigen die palliativmedizinische Versorgung sinnvoll ergänzen. Der Bedarf scheint v. a. unter der Woche zu den Hauptarbeitszeiten zu liegen.

Zusammenfassung Hintergrund Orale Tyrosinkinaseinhibitor (TKI)-Therapien werden zunehmend wichtiger in der Therapie maligner Erkrankungen. Die Therapiekontrolle mit Fokus auf Adharenz, Nebenwirkungen und Interaktionen stellt die Medizin vor neue Herausforderungen. Die Rolle und die Moglichkeiten von Hausarzt*innen in der Versorgung von TKI-Patient*innen sind bislang unklar und sollen in einer deutschlandweiten Umfrage erfasst werden. Methode Von April - Juli 2016 wurden 3.000 Hausarzt*innen in Deutschland schriftlich zu den Moglichkeiten einer Mitbetreuung von TKI-Patient*innen befragt. Ergebnisse Der Rucklauf betrug 18% (n = 553). Der Altersgipfel lag zwischen 50-60 Jahren. 81% waren Allgemeinarzt*innen, 14% Internist*innen und 5% Praktische Arzt*innen. 98% betreuten keine oder weniger als 10 TKI-Patient*innen pro Quartal. Das Wissen um Nebenwirkungen und Interaktionspotential von TKI war bei uber 90% gering. 83% bevorzugten eine Therapiekontrolle durch den behandelnden Facharzt*in und 93% fuhlten sich unsicher in der Therapiekontrolle. Die TKI-Adharenzkontrolle nahm bei 66% einen geringen Stellenwert ein. Die Zahl der betreuten TKI-Patienten*innen hatte einen wesentlichen Einfluss auf Wissen und Betreuungsmoglichkeiten. Wissen uber TKI und Sicherheit in der Therapiekontrolle korrelierten signifikant. Jungere Arzt*innen zeigten sich tendenziell sicherer in Therapiekontrollen. Internist*innen hatten tendenziell mehr Kenntnisse als Allgemeinarzt*innen und Praktische Arzt*innen. Diskussion Niedrige TKI-Patient*innenzahlen, geringes Wissen uber TKI und Wunsch nach facharztlicher Betreuung schranken aktuell die Moglichkeiten zur Mitversorgung von TKI-Patient*innen durch Hausarzt*innen ein. Schlussfolgerung Trotz einer grundsatzlichen Motivation zur Betreuung von Tumorpatient*innen scheinen routinemasige Therapiekontrollen von TKI-Patient*innen durch Hausarzt*innen aktuell kaum umzusetzen und sollte zurzeit bei den betreuenden Facharzt*innen verbleiben.

Few data exist on health-related quality of life (QoL) in patients with metastatic pancreatic cancer (mPC) receiving first-line chemotherapy (Awad L ZE, Mesbah M Boston, MA. Applying survival data methodology to analyze quality of life data, in Mesbah M, Cole BF, Ting Lee M-L (eds): Statistical Methods for Quality of Life Studies: Design, Measurements and Analysis. Kluwer Academic Publishers 2002). The QOLIXANE study is a prospective, noninterventional, multicenter substudy of the Platform for Outcome, Quality of Life and Translational Research on Pancreatic Cancer (PARAGON) registry, which evaluated QoL in patients with mPC receiving first-line gemcitabine and nab-paclitaxel chemotherapy in real-life setting. QoL was prospectively measured via EORTC QLQ-C30 questionnaires at baseline and every month thereafter. Therapy and efficacy parameters were prospectively collected. Main objectives were the rate of patients without deterioration of Global Health Status/QoL (GHS/QoL) at 3 and 6 months. Six hundred patients were enrolled in 95 German study sites. Median progression-free survival was 5.9 months (95% confidence interval [CI], 5.2-6.3). Median overall survival (OS) was 8.9 months (95% CI, 7.9-10.2), while median time to deterioration of GHS/QoL was 4.7 months (95% CI, 4.0-5.6). With a baseline GHS/QoL score of 46 (SD, 22.8), baseline QoL of the patients was severely impaired, in most cases due to loss in role functioning and fatigue. In the Kaplan-Meier analysis, 61% and 41% of patients had maintained GHS/QoL after 3 and 6 months, respectively. However, in the QoL response analysis, 35% and 19% of patients had maintained (improved or stable) GHS/QoL after 3 and 6 months, respectively, while 14% and 9% had deteriorated GHS/QoL with the remaining patients being nonevaluable. In the Cox regression analysis, GHS/QoL scores strongly predicted survival with a hazard ratio of 0.86 (P < .0001). Patients with mPC have poor QoL at baseline that deteriorates within a median of 4.7 months. Treatment with gemcitabine and nab-paclitaxel is associated with maintained QoL in relevant proportions of patients. However, overall, results remain poor, reflecting the aggressive nature of the disease.

ZusammenfassungDer Onko-Nexus („Kümmererprojekt“), gefördert vom Bayerischen Staatsministerium für Gesundheit und Pflege, widmet sich der Verbesserung der ambulanten/stationären Schnittstellenproblematik für Patienten mit hochkomplexen malignen Erkrankungen, die einen Aufenthalt an einem universitären Zentrum benötigten. Die Patienten wurden von einer ambulanten und einer stationären „Kümmerin“ (medizinische Fachangestellte) mitbetreut. Zusätzlich wurde vom universitären Zentrum eine Spezialsprechstunde in der heimatnahen onkologischen Praxis angeboten. Während der 3-jährigen Laufzeit konnten 26 Patienten in das Projekt eingeschlossen werden. Nach Abschluss des Projektes wurden 9 Patienten und die 2 „Kümmerinnen“ mittels qualitativer Leitfadeninterviews befragt. Die Patienten profitierten v. a. von der intensivierten Betreuung, der Vermeidung von Fahrstrecken und dem engen Kontakt zwischen Klinik und Praxis. Das Projekt wirkte sich deutlich positiv auf die Lebensqualität der Patienten aus.

Background: The introduction of targeted agents has revolutionized the treatment of CLL but only few patients achieve complete remissions and minimal residual disease negativity with ibrutinib monotherapy. Methods: This multicentre, investigator-initiated phase-II study evaluates a sequential treatment with two cycles of bendamustine debulking for patients with a higher tumour load, followed by ofatumumab and ibrutinib induction and maintenance treatment. An all-comer population, irrespective of prior treatment, physical fitness and genetic factors was included. The primary endpoint was the investigator assessed overall response rate at the end of induction treatment. Findings: Of 66 patients enrolled, one patient with early treatment discontinuation was excluded from the efficacy analysis as predefined by the protocol. Thirty-nine patients (60%) were treatment-naive and 26 patients (40%) had relapsed/refractory CLL, 21 patients (32%) had a del(17p) and/or TP53 mutation and 45 patients (69%) had an unmutated IGHV status. At the end of the induction, 60 of 65 patients (92%) responded and 9 (14%) achieved minimal residual disease (MRD) negativity (

The heterogeneity of early stage CLL challenges prognostication, and refinement of prognostic indices for risk-adapted management in this population is essential. The aim of the multicenter, prospective CLL1 trial was to explore a novel prognostic model (CLL1-PM) developed to identify risk groups, separating patients with favorable from others with dismal prognosis. A cohort of 539 clinically, biochemically, and genetically characterized Binet stage A patients were observed until progression, first-line treatment, or death. Multivariate analysis identified six independent factors associated with overall survival (OS) and time-to-first treatment (TTFT): del(17p), unmutated IGHV, del(11q), ß2-microglobulin3.5 mg/dL, lymphocyte doubling time (LDT)12 months, and age60 years. These factors were integrated into the CLL1-PM, which stratified patients into four risk groups. The CLL1-PM was prognostic for OS and TTFT, e.g., the risk of treatment at 5 years was 85.9, 51.8, 27.6, and 11.3% for very low (0-1.5), low (2-4), high (4.5-6.5), and very high-risk (7-14) scores, respectively (P 0.001). Notably, in addition to factors comprising CLL-IPI, we substantiated del(11q) and LDT as prognostic factors in early CLL. Altogether, our findings would be useful to effectively stratify Binet stage A patients, particularly within the scope of clinical trials evaluating novel agents.

Zusammenfassung Ziel der Studie Neben der palliativmedizinischen Versorgung fordern die Deutsche und die Europäische Gesellschaft für Palliativmedizin die Berücksichtigung der sozialen Bedürfnisse von Patienten mit weit fortgeschrittenen und unheilbaren Erkrankungen. Soziale Isolation kann die Lebensqualität und den Krankheitsverlauf verschlechtern oder zur Verkürzung der Lebensdauer führen. Diese Arbeit soll den Effekt eines Integrationsprojekts auf den persönlichen (Lebensqualität, Selbstsicherheit, Krankheitsbewältigung) und sozialen (gesellschaftliche Reintegration) Nutzen für Palliativpatienten analysieren. Methodik Im Anschluss an eine mehrtägige Reise für Palliativpatienten nach Rom wurden 17 Teilnehmer und sieben Betreuer zum soziopsychologischen Gewinn mittels audioregistrierter telefonischer Leitfadeninterviews befragt. Die Interviews wurden transkribiert und in einem mehrstufigen Prozess inhaltsanalytisch ausgewertet und zusammengefasst. Ergebnisse Eine organisierte Reise steigerte die soziale Integration, Lebensqualität und Selbstsicherheit von Palliativpatienten und führte zu einer besseren Krankheitsbewältigung. Schlussfolgerung Die Aussagen von Patienten und Betreuern spiegeln die Notwendigkeit und den Nutzen der gesellschaftlichen Integration von Palliativpatienten wider.

Background: Oral antiproliferative therapies have become increasingly important in the treatment of tumors. To ensure patient safety, medical care is focused on adherence and side effects. Objectives: To meet increased personnel and time requirements, delegation of tasks to nonmedical specialists (NMS) may be a solution; however, presently, little is known about the options in Germany. Method: At least 3,300 members of the German Society for Hematology and Medical Oncology (DGHO), 580 members of the Professional Association of Office-Based Hematologists and Oncologists in Germany (BNHO), and 1,500 members of the Conference on Oncology Nursing and Pediatric Nursing (KOK) were contacted via a web-based survey. The survey focused on the feasibility of oncology nurse consultation as an additional consulting service for patients undergoing oral tumor therapy. Results: In total, 255 (physicians) and 206 (NMS) questionnaires were evaluable; 90.9% of the physicians were hematologists/oncologists, 87.8% advocated oncology nurse consultation, 34.1% had previously implemented/scheduled such consultations, 58.3% of the NMS were nursing staff, 46.1% had advanced training in oral tumor therapy, 94.2% were interested in further qualifications, 37.8% worked at facilities with established/planned nurse consultations, and 62.1% personally conducted/preferred conducting consultations. Conclusions: Throughout Germany, there seems to exist a group of qualified NMS who are motivated to provide care to patients undergoing oral tumor therapy. Particular physicians actively support these nurse consultations. Extensive implementation of delegation concepts in standard care of patients undergoing oral tumor therapy is not yet underway.

Few data exist on health-related quality of life (QoL) in patients with metastatic pancreatic cancer (mPC) receiving first-line chemotherapy (Awad L ZE, Mesbah M Boston, MA. Applying survival data methodology to analyze quality of life data, in Mesbah M, Cole BF, Ting Lee M-L (eds): Statistical Methods for Quality of Life Studies: Design, Measurements and Analysis. Kluwer Academic Publishers 2002). The QOLIXANE study is a prospective, noninterventional, multicenter substudy of the Platform for Outcome, Quality of Life and Translational Research on Pancreatic Cancer (PARAGON) registry, which evaluated QoL in patients with mPC receiving first-line gemcitabine and nab-paclitaxel chemotherapy in real-life setting. QoL was prospectively measured via EORTC QLQ-C30 questionnaires at baseline and every month thereafter. Therapy and efficacy parameters were prospectively collected. Main objectives were the rate of patients without deterioration of Global Health Status/QoL (GHS/QoL) at 3 and 6 months. Six hundred patients were enrolled in 95 German study sites. Median progression-free survival was 5.9 months (95% confidence interval [CI], 5.2-6.3). Median overall survival (OS) was 8.9 months (95% CI, 7.9-10.2), while median time to deterioration of GHS/QoL was 4.7 months (95% CI, 4.0-5.6). With a baseline GHS/QoL score of 46 (SD, 22.8), baseline QoL of the patients was severely impaired, in most cases due to loss in role functioning and fatigue. In the Kaplan-Meier analysis, 61% and 41% of patients had maintained GHS/QoL after 3 and 6 months, respectively. However, in the QoL response analysis, 35% and 19% of patients had maintained (improved or stable) GHS/QoL after 3 and 6 months, respectively, while 14% and 9% had deteriorated GHS/QoL with the remaining patients being nonevaluable. In the Cox regression analysis, GHS/QoL scores strongly predicted survival with a hazard ratio of 0.86 (P .0001). Patients with mPC have poor QoL at baseline that deteriorates within a median of 4.7 months. Treatment with gemcitabine and nab-paclitaxel is associated with maintained QoL in relevant proportions of patients. However, overall, results remain poor, reflecting the aggressive nature of the disease.

The creation of antitumor agents with an oral or subcutaneous route of administration has had important positive implications in the development of drugs to treat cancers, but issues such as false drug intake, uncontrolled side effects, and limited supervision may jeopardize the ability of these agents to improve treatment. A potential solution is the recruitment of non-physician healthcare professionals (i.e., nurses and physician assistants) and a special training course for them that focuses on the improvement of patient compliance. We developed and implemented three special professional training modules for non-physician healthcare professionals, which focus on the pharmacological aspects and side effects of oral and subcutaneous antitumor medications in regard to management strategies and communication issues that these non-physician healthcare professionals should address. Subsequently, we administered a questionnaire survey evaluating the course content and the implementation of the course in practice to the training participants to collect data for its implementation. Of 165 questionnaires that were administered, 44 (27%) were answered. The participants rated the course as being highly useful for their daily work. The participants reported a significant improvement in their professional expertise from the course. They emphasized the importance of medical topics and practical content to be included in the course delivery. The course encouraged 75% of the responders to start independent consultations with cancer patients that focused on questions of medication adherence for oral and subcutaneous antitumor medications, as well as the management of their side effects. Based on our results, at least a portion of the non-physician healthcare workforce is highly interested in engaging in active and autonomous co-supervision of patients who are treated with oral and subcutaneous antitumor medications. In addition to the theoretical basics of the treatment modalities, educational courses on oral and subcutaneous antitumor medications for non-physician healthcare professionals should focus on practical training and topics relevant to patient care.

The Onko-Nexus ("Caretaker-Project"), sponsored by the Bavarian Ministry for Health and Nursing, is dedicated to improving the outpatient/hospitalized care interface issue for patients with highly complex malignant diseases requiring inpatient care in a university hospital. A total of 26 patients were recruited during the 3-year period of the project. The patients were managed and supported by 2 "Caretakers" (physician assistants), one from the outpatient unit and one working in the wards. Additionally, the university hospital provided a special consultation hour in an oncological private practice close to patient's home. After completion of the project, 9 patients and the 2 "Caretakers" were interviewed via guided qualitative interviews. The main benefits for the patients were intensive support, avoiding long journeys and the close contact between hospital and private practice. The project had a clear positive effect on the patients' quality of life.Der Onko-Nexus („Kümmererprojekt“), gefördert vom Bayerischen Staatsministerium für Gesundheit und Pflege, widmet sich der Verbesserung der ambulanten/stationären Schnittstellenproblematik für Patienten mit hochkomplexen malignen Erkrankungen, die einen Aufenthalt an einem universitären Zentrum benötigten. Die Patienten wurden von einer ambulanten und einer stationären „Kümmerin“ (medizinische Fachangestellte) mitbetreut. Zusätzlich wurde vom universitären Zentrum eine Spezialsprechstunde in der heimatnahen onkologischen Praxis angeboten. Während der 3-jährigen Laufzeit konnten 26 Patienten in das Projekt eingeschlossen werden. Nach Abschluss des Projektes wurden 9 Patienten und die 2 „Kümmerinnen“ mittels qualitativer Leitfadeninterviews befragt. Die Patienten profitierten v. a. von der intensivierten Betreuung, der Vermeidung von Fahrstrecken und dem engen Kontakt zwischen Klinik und Praxis. Das Projekt wirkte sich deutlich positiv auf die Lebensqualität der Patienten aus.

Background The objective of the IMPROVE study was patients’ preference for either endocrine-based therapy or combined chemo- and anti-angiogenic therapy in advanced HR-positive/HER2-negative breast cancer. Methods In this randomized, cross-over phase IV study, 77 patients were recruited in 26 sites in Germany. Patients were randomized 1:1 to receive either capecitabine plus bevacizumab (Cap+Bev) as first-line therapy followed by cross-over to everolimus plus exemestane (Eve+Exe) as second-line therapy (Arm A) or the reverse sequence (Arm B). The primary endpoint was patients’ preference for either regimen, assessed by the Patient Preference Questionnaire 12 weeks after cross-over. Key secondary endpoints included progression-free survival (PFS), overall survival (OS), safety, and quality of life (QoL). Results 61.5% of patients preferred Cap+Bev (p = 0.1653), whereas 15.4% preferred Eve+Exe and 23.1% were indecisive. Physicians showed a similar tendency towards Cap+Bev (58.1%) as the preferred regimen versus Eve+Exe (32.3%). Median first-line PFS was longer for Cap+Bev than for Eve+Exe (11.1 months versus 3.5 months). Median second-line PFS was similar between Cap+Bev and Eve+Exe (3.6 months versus 3.7 months). Median OS was comparable between Arm A (28.8 months) and Arm B (24.7 months). 73.0% and 52.6% (first−/second-line, Cap+Bev) and 54.1% and 52.9% (first−/second-line, Eve+Exe) of patients experienced grade 3/4 TEAEs. No treatment-related deaths occurred. QoL and treatment satisfaction were not significantly different between arms or treatment lines. Conclusions Patients tended to favor Cap+Bev over Eve+Exe, which was in line with physicians’ preference. Cap+Bev showed superior first-line PFS, while QoL was similar in both arms. No new safety signals were reported. Trial registration EudraCT No: 2013–005329-22. Registered on 19 August 20

Das hier dargestellte ASV-Team versorgt derzeit Patienten mit gastrointestinalen sowie gynakologischen Tumoren.

In metastatic colorectal cancer (mCRC), liver-limited disease (LLD) is associated with a higher chance of metastectomy leading to long-term survival. However, limited data describes the prognostic and predictive relevance of initially unresectable LLD with regard to targeted first-line therapy. The present analysis investigated the relevance of initially unresectable LLD in mCRC patients treated with targeted therapy against either the epidermal growth factor receptor (EGFR) or vascular epithelial growth factor (VEGF). The analysis was performed based on FIRE-3, a randomized phase III trial comparing first-line chemotherapy with FOLFIRI plus either cetuximab (anti-EGFR) or bevacizumab (anti-VEGF) in RAS wild-type (WT) mCRC. Of 400 patients, 133 (33.3%) had LLD and 267 (66.8%) had non-LLD. Median overall survival (OS) was significantly longer in LLD compared to non-LLD patients (36.0 vs. 25.4 months; hazard ratio [HR] = 0.66; 95% confidence interval [CI]: 0.51-0.87; p = 0.002). In a multivariate analysis also including secondary hepatic resection as time-dependent variable, LLD status was independently prognostic for OS (HR = 0.67; 95% CI: 0.50-0.91; p = 0.01). As assessed by interaction tests, treatment benefit from FOLFIRI plus cetuximab compared to FOLFIRI plus bevacizumab was independent of LLD status with regard to objective response rate (ORR), early tumour shrinkage ≥20% (ETS), depth of response (DpR) and OS (all p > 0.05). In conclusion, LLD could be identified as a prognostic factor in RAS-WT mCRC, which was independent of hepatic resection in patients treated with targeted therapy. LLD had no predictive relevance since benefit from FOLFIRI plus cetuximab over bevacizumab was independent of LLD status.

// Melanie Kripp 1, * , Nicole Prasnikar 2, * , Ursula Vehling-Kaiser 3 , Julia Quidde 4 , Salah-Eddin Al-Batran 5 , Alexander Stein 4 , Kai Neben 6 , Carla Verena Hannig 7 , Hans Werner Tessen 8 , Tanja Trarbach 9 , Axel Hinke 10 and Ralf-Dieter Hofheinz 11 1 Medizinische Klinik 3, Hamatologie und Onkologie, Universitatsmedizin Mannheim, Mannheim, Germany 2 Hamatologie, Internistische Onkologie und Palliativmedizin, Asklepios Klinik Barmbek, Hamburg, Germany 3 Tagesklinik fur Hamatologie, Onkologie, Palliativmedizin, Landshut, Germany 4 Universitares Cancer Center, UKE Hamburg, Hamburg, Germany 5 Universitares Centrum fur Tumorerkrankungen, Krankenhaus Nordwest, Frankfurt, Germany 6 Medizinische Klinik II, Klinikum Mittelbaden, Baden-Baden, Germany 7 Onkologisches Gemeinschaftspraxis, Bottrop/Dorsten, Germany 8 Onkologische Kooperation Harz, Goslar, Germany 9 Zentrum fur Tumorbiologie und Integrative Medizin, Klinikum Wilhelmshaven, Wilhelmshaven, Germany 10 WiSP Wissenschaftlicher Service Pharma GmbH, Langenfeld, Germany 11 Interdisziplinares Tumorzentrum, Universitatsmedizin Mannheim, Universitat Heidelberg, Heidelberg, Germany * These authors have contributed equally to this work Correspondence to: Melanie Kripp, email: melanie.kripp@medma.uni-heidelberg.de Keywords: doxycycline, erythromycin, panitumumab, skin toxicity, WoMo score Received: July 12, 2017 Accepted: August 08, 2017 Published: September 23, 2017 ABSTRACT Background: Dermatologic toxicities, especially akne-like skin rash, are the most common side-effects associated with anti-epidermal growth factor receptor (EGFR) therapy. Preemptive treatment with oral tetracyclines is recommended as a standard. Topical prophylactic options have thus far not been compared to tetracyclines. In the current study, we sought to establish an alternative topical treatment. Patients and methods: In this multicentre, randomized, open-label phase II study patients with (K)Ras-wildtype colorectal cancer receiving panitumumab were randomized (1:1) to receive either doxycycline 100 mg b.i.d. (standard arm) or erythromycin ointment 2% followed by doxycycline in case of insufficient activity. The primary endpoint was the percentage of patients developing no skin toxicity ≥ grade 2 at any time during the first 8 weeks of panitumumab treatment. Skin toxicity was assessed using the NCI CTCAE v 4.0. Secondary endpoints comprised the assessment of skin toxicity using a more thorough grading system (WoMo score), evaluation of skin-related (DLQI) and global quality of life (EORTC QLQ C30). Results: In total, 88 patients were included in this trial. 69% of the patients in the erythromycin arm suffered from skin toxicity of grade ≥ 2 versus 63% in the standard arm ( P = n.s. ). However, as per WoMo score significantly more patients in the erythromycin arm developed moderate or severe skin toxicity at earlier time points. Skin related and overall quality of life was comparable between both arms. Conclusions: Based on this data erythromycin cannot be regarded as an alternative to doxycycline as prevention of EGFR-related skin toxicity.

Early, risk-adapted treatment with fludarabine in Binet stage A chronic lymphocytic leukemia patients: results of the CLL1 trial of the German CLL study group

Our aim was to explore the impact of the HER2/neu, HER3 receptor as well as their ligands' neuregulin (NRG1) expression on the outcome of patients with metastatic colorectal cancer (mCRC). NRG1, HER2/neu and HER3 expression was evaluated in 208 patients with mCRC receiving 5-FU/LV plus irinotecan or irinotecan plus oxaliplatin as the first-line treatment. Biomarker expression was correlated with the outcome of patients. NRG1 (low: 192 vs. high: 16), HER2/neu (low: 201 vs. high: 7) and HER3 (low: 69 vs. high: 139) expressions were assessed in 208 patients. High versus low NRG1 expression significantly affected progression-free survival (PFS) [4.7 vs. 8.2 months, hazard ratio (HR): 2.45; 95% confidence interval (CI): 1.45-4.13; P=0.001], but not overall survival (OS) (15.5 vs. 20.7 months, HR: 1.33; 95% CI: 0.76-2.35; P=0.32). High versus low HER3 expression (PFS: 7.1 vs. 8.8 months, HR: 1.11; 95% CI: 0.82-1.50; P=0.50; OS: 19.8 vs. 21.1 months, HR: 0.95; 95% CI: 0.70-1.30; P=0.75) and high compared with low HER2/neu expression (PFS: 7.7 vs. 8.0 months, HR: 1.07; 95% CI: 0.71-1.60; P=0.75; OS: 16.6 vs. 21.1 months, HR: 1.13; 95% CI: 0.75-1.71; P=0.57) did not influence outcome. High NRG1 expression was associated with inferior PFS in the FIRE-1 trial. We did not detect a prognostic impact of HER2/neu and HER3 overexpression in mCRC. The frequency of overexpression was comparable with other studies.

We explored the association of early tumor shrinkage (ETS) and non-ETS with efficacy of first-line and consecutive second-line treatment in patients with KRAS wild-type metastatic colorectal cancer treated in FIRE-3. Assessment of tumor shrinkage was based on the sum of longest diameters of target lesions, evaluated after 6 weeks of treatment. Shrinkage was classified as ETS (shrinkage by ≥ 20%), mETS (shrinkage by 0 to20%), mPD (minor progression0 to20%) and PD (progression ≥20%). Overall survival (OS) was 33.2 (95% CI 28.0-38.4) months in ETS patients, while non-ETS was associated with less favorable outcome (mETS 24.0 (95% CI 21.2-26.9) months, mPD 19.0 (95% CI 13.0-25.0) months, PD 12.8 (95% CI 11.1-14.5) months). Differences in PFS of first-line therapy were less pronounced. ETS subgroups defined in first-line therapy also correlated with efficacy of second-line therapy. Progression-free survival in second-line (PFS2nd) was 6.5 months (5.8-7.2) for ETS, and was 5.6 (95% CI 4.7-6.5) months for mETS, 4.9 (95% CI 3.7-6.1) months for mPD and 3.3 (95% CI 2.3-4.3) months for PD. PFS of first-line and PFS2nd showed a linear correlation (Bravais-Pearson coefficient: 0.16, p = 0.006). While ETS is associated with the most favorable outcome, non-ETS represents a heterogeneous subgroup with distinct characteristics of less favorable initial tumor response to treatment. This is the first analysis to demonstrate that early tumor response observed during first-line FOLFIRI-based therapy may also relate to efficacy of second-line treatment. Early response parameters may serve as stratification factors in trials recruiting pretreated patients.

INTRODUCTION Chronic lymphocytic leukemia (CLL) is frequently associated with an impaired humoral and cellular immunity. On a global scale chemoimmunotherapy (CIT) has remained one of the most frequently used treatment option. Thus, patients (pts) may experience further cytopenia, particularly treatment-related neutropenia, increasing the risk of infections. In order to better characterize incidence, characteristics and outcomes of infections during and after therapy, a pooled analysis of phase II and III German CLL Study Group trials was performed. METHODS Data of first line pts from 5 clinical trials (CLL7, pts treated with fludarabine, cyclophosphamide, rituximab [FCR]; CLL8, FC vs FCR; CLL10, FCR vs bendamustine-rituximab [BR]; CLL11, chlorambucil [CLB] vs CLB-R vs CLB-Obinutuzumab [CLB-Ob] and CLL2M, BR) were analyzed. Clinical, laboratory, genetic and event-related data were pooled. Infections defined as severe (CTC grade 3-5) from initiation of therapy until 4 weeks after completion of study treatment were considered related. Due to varying reporting periods for infections of the respective trials later events of infections were not included. Kaplan-Meier curves for landmark overall survival (OS) from completion of study treatment plus 4 weeks were plotted and compared by non-stratified log-rank test. Hazard ratios (HR) and 95% confidence intervals (CI) were calculated using Cox proportional-hazard regression modelling. RESULTS Data from 2,291 pts receiving at least one dose of CIT were pooled. Median observation time was 71.7 months, ranging between 43.7 months (CLL2M) and 81.0 months (CLL10). Seven-hundred and twenty-seven pts received FCR, 396 pts FC, 395 pts BR, 116 pts CLB, 326 pts CLB-R and 331 pts CLB-Ob. Overall, 274 severe grad 3/4/5 infections were reported in 229 pts (10.0% of 2,291 pts). Of those 189 pts (82.5%) had max. grade 3 infections, 22 (9.6%) pts had grade 4 infections and 18 (7.9%) pts died due to infectious complications. Median time to severe infection from start of treatment was 1.8 months (IQR 0.9-3.6), with a median number of infectious episodes per patient of 1 (range 1-4). Thirty-one (13.5%) of 229 pts had bacterial infections, 35 (15.3%) viral infections, 5 (2.2%) fungal infections and 172 (75.1%) unspecified infections. Higher grade (i.e. ≥ CTC grade 3) leukopenia and/or neutropenia was reported in 121 (52.8%) pts with severe infections. Eighty-eight (12.1%) of FCR treated pts had severe infections, followed by BR 45 (11.4%), CLB 12 (10.3%), FC 35 (8.8%), CLB-Ob 25 (7.6%) and CLB-R 24 (7.4%). Median age was 64 years in the entire cohort; no differences between pts with and without infections were observed with regards to age, sex, ECOG or creatinine clearance. Molecular and cytogenetic characteristics (deletion 17p, deletion 11q, trisomy 12) and IGHV status were similarly distributed between both groups. Median neutrophil count at enrolment was 4.4x10-9/l in both groups, respectively. Prior to therapy, levels of immunoglobulin were comparable between pts with and without infections (median IgG 7.0 vs 7.5 g/L, IgM 0.3 g/L vs 0.3 g/L). Also, pts with at least one episode of ≥ CTC grade 3 leukopenia/neutropenia had comparable rates of severe infections to pts without higher grade leukopenia/neutropenia (147 [53.6%] vs 127 [46.4%] pts). No differences were observed between pts with or without infections regarding the response to first line treatment (183 pts [79.9%] with complete response or partial response to treatment vs 1715 pts [83.2%]) as well as the rate of undetectable minimal residual disease levels (50 [21.8%] vs 477 [23.1%]). Overall survival from 4 weeks after completion of study treatment was significantly shorter in pts with severe infections compared to pts without severe infections (median 73.7 months vs 97.3 months, HR 1.503, 95% CI 1.217-1.856, p < 0.001). CONCLUSION This analysis confirms that prognosis of CLL pts who received first line treatment with (immuno)chemotherapy is influenced by severe infections. This risk does not correlate with the explored cyto- or molecular genetic risk factors, nor with response to treatment, pre-therapeutic levels of immunoglobulins or occurrence of higher grade neutropenia. Pts who experience severe infections have a significantly shorter overall survival compared to pts without severe infections. Due to their vulnerability, careful management of infectious complications in CLL pts is warranted. Figure 1 Disclosures Al-Sawaf: AbbVie: Consultancy, Honoraria, Other: personal fees, Research Funding; Janssen: Consultancy, Honoraria, Other: personal fees, Research Funding; AstraZeneca: Consultancy, Honoraria, Other: personal fees; BeiGene: Research Funding; Roche: Consultancy, Honoraria, Other: personal fees, Research Funding; Gilead: Consultancy, Honoraria, Other: personal fees. Fink:Janssen: Honoraria; Celgene: Research Funding; AbbVie: Other: travel grants. Cramer:F. Hoffmann-LaRoche: Honoraria, Other: travel support, Research Funding; AstraZeneca: Consultancy, Honoraria, Other: travel support, Research Funding; Acerta: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen-Cilag: Consultancy, Honoraria, Other: travel support, Research Funding; Beigene: Research Funding; Novartis: Consultancy, Research Funding; Gilead: Other: travel support, Research Funding; AbbVie: Honoraria, Other: travel support. Herling:Roche: Other: Travel support, Research Funding. Von Tresckow:Janssen-Cilag: Honoraria, Other: travel grants, Research Funding; Celgene: Other: travel grants; F. Hoffmann-LaRoche: Honoraria, Other: travel grants, Research Funding; AbbVie: Honoraria. Böttcher:Novartis: Honoraria; AbbVie: Honoraria, Research Funding; Celgene: Research Funding; Janssen: Honoraria, Research Funding; Roche: Consultancy, Honoraria, Research Funding. Dreyling:Astra Zeneca: Consultancy; Abbvie: Research Funding; Roche: Consultancy, Research Funding, Speakers Bureau; Bayer: Consultancy, Speakers Bureau; Beigene: Consultancy; Gilead: Consultancy, Research Funding, Speakers Bureau; Janssen: Consultancy, Research Funding, Speakers Bureau; Novartis: Consultancy; Celgene: Consultancy, Research Funding, Speakers Bureau. Jaeger:F. Hoffmann-La Roche: Honoraria, Research Funding; Gilead: Honoraria, Research Funding; BMS/Celgene: Consultancy, Honoraria, Research Funding; Infinity: Honoraria; Takeda: Honoraria; Amgen: Honoraria; Karyopharm: Honoraria; CDR Life AG: Consultancy, Research Funding; Miltenyi: Consultancy, Honoraria; True North: Honoraria, Research Funding; AbbVie: Honoraria; Novartis: Consultancy, Honoraria, Research Funding. Gregor:Roche: Honoraria; Mundipharma: Honoraria; AbbVie: Honoraria; Amgen: Honoraria; Celgene: Honoraria; Janssen: Honoraria; Pfizer: Honoraria. Ritgen:Pfizer: Consultancy, Honoraria; BMS: Consultancy, Honoraria, Other: travel grants; F. Hoffman-La Roche: Consultancy, Honoraria, Other: travel grants, Research Funding; Gilead: Other: travel grants. Dürig:Janssen: Consultancy; AbbVie: Consultancy; Celgene: Consultancy. Tausch:AbbVie: Consultancy, Honoraria, Research Funding; Janssen-Cilag: Consultancy, Honoraria, Research Funding; Roche: Consultancy, Honoraria, Research Funding. Stilgenbauer:GlaxoSmithKline: Consultancy, Honoraria, Other: travel support, Research Funding; Janssen-Cilag: Consultancy, Honoraria, Other: travel support, Research Funding; Mundipharma: Consultancy, Honoraria, Other, Research Funding; Gilead: Consultancy, Honoraria, Other: travel support, Research Funding; Genzyme: Consultancy, Honoraria, Other: travel support, Research Funding; Novartis: Consultancy, Honoraria, Other, Research Funding; Pharmacyclics: Consultancy, Honoraria, Other, Research Funding; Genentech: Consultancy, Honoraria, Other: travel support, Research Funding; F. Hoffmann-LaRoche: Consultancy, Honoraria, Other: travel support, Research Funding; Celgene: Consultancy, Honoraria, Other: travel support, Research Funding; Boehringer-Ingelheim: Consultancy, Honoraria, Other: travel support, Research Funding; Amgen: Consultancy, Honoraria, Other: travel support, Research Funding; AbbVie: Consultancy, Honoraria, Other: travel support, Research Funding. Wendtner:Janssen-Cilag: Consultancy, Honoraria, Other: travel support, Research Funding; GlaxoSmithKline: Consultancy, Honoraria, Other: travel support, Research Funding; Gilead: Consultancy, Honoraria, Other: travel support, Research Funding; Genentech: Consultancy, Honoraria, Other: travel support, Research Funding; Hoffmann-LaRoche: Consultancy, Honoraria, Other: travel support, Research Funding; AbbVie: Consultancy, Honoraria, Other: travel support, Research Funding; Mundipharma: Consultancy, Honoraria, Other: travel support, Research Funding; Pharmacyclics: Consultancy, Honoraria, Other: travel support, Research Funding. Fischer:F. Hoffmann-La Roche: Honoraria, Other: travel grants; AbbVie: Honoraria. Goede:AbbVie: Membership on an entity's Board of Directors or advisory committees; F. Hoffmann-LaRoche: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel grants; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel grants; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees. Hallek:F. Hoffmann-LaRoche: Consultancy, Honoraria, Research Funding; AbbVie: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Mundipharma: Consultancy, Honoraria, Research Funding; Gilead: Consultancy, Honoraria, Research Funding. Eichhorst:Oxford Biomedica: Consultancy, Honoraria, Other: travel support, Research Funding; AstraZeneca: Consultancy, Honoraria, Other: travel support, Research Funding; Gilead: Consultancy, Honoraria, Other: travel support, Research Funding; BeiGene: Consultancy, Honoraria, Other: travel support, Research Funding; ArQule: Consultancy, Honoraria, Other: travel support, Research Funding; Novartis: Consultancy, Honoraria, Other: travel support, Research Funding; Celgene: Consultancy, Honoraria, Other: travel support, Research Funding; Janssen-Cilag: Consultancy, Honoraria, Other: travel support, Research Funding; AbbVie: Consultancy, Honoraria, Other: travel support, Research Funding; F. Hoffmann-LaRoche: Consultancy, Honoraria, Other: travel support, Research Funding. Langerbeins:AbbVie: Honoraria, Other: travel grants, Research Funding; F. Hoffmann-LaRoche: Honoraria, Other: travel grants, Research Funding; Janssen-Cilag: Honoraria, Other: travel grants, Research Funding; Mundipharma: Honoraria, Other: travel grants, Research Funding.

Oral tyrosine kinase inhibitor (TKI) therapies are becoming increasingly more important in the treatment of malignant diseases. Monitoring with focus on adherence, side effects and interactions poses new challenges for medical care. The role and capabilities of family doctors in the care of TKI patients are yet unclear and should be uncovered in a nationwide survey.From April to July 2016, 3,000 family doctors in Germany were asked to complete a written questionnaire regarding their capabilities for co-supervision of TKI patients.The response rate was 18% (n=553). The peak age was between 50 and 60 years. 81% were specialists in general medicine, 14% specialists in internal medicine and 5% general practitioners. 98% cared for no or less than 10 TKI patients per quarter. Knowledge of side effects and interaction potential of TKIs was low in over 90%. 83% preferred monitoring by the treating oncologist and 93% felt uncertain about treatment monitoring. The control of adherence was of little importance in 66%. The number of treated TKI patients had a significant impact on knowledge and opportunities for treatment monitoring. There was a significant correlation between knowledge about TKIs and confidence in treatment monitoring. In general, younger doctors tended to be more confident in treatment monitoring, and specialists in internal medicine tended to have more knowledge than specialists in general medicine general practitioners and general practitioners.Currently, the low number of TKI patients, little knowledge about TKI, and the desire for specialist care are limiting the possibilities of co-caring for TKI patients by family doctors.Although family doctors are generally motivated to care for tumor patients, routine treatment controls of TKI patients conducted by family doctors seem hardly possible at the moment and should currently remain with the specialist.

3552 Background: Prognostic biomarkers beside RAS/BRAF status are necessary to identify metastatic colorectal cancer (mCRC) patients who benefit from combined (COMB) versus sequential (SEQ) treatment with fluoropyrimidine, bevacizumab and irinotecan (randomized phase III XELAVIRI trial). Methods: mRNA was extracted from formalin-fixed paraffin embedded (FFPE) tumor tissue of 337 patients, gene expression was measured by the Nanostring PanCancer Progression Panel. Consensus molecular subtypes (CMS) classification was re-derived using a multinomial regression model. Data of Guinney et al. (Nat. Med. 2015. 21:1350-6) and FIRE-3 served as training and validation set. RAS/BRAF MUT were assessed by pyrosequencing. Median overall (OS) and progression free survival (PFS), hazard ratios (HR) and 95% confidence interval (CI) were estimated by Kaplan-Meier method and univariate Cox regression. Results: The multinomial regression model employed in the present analysis correctly predicted CMS labels in 98.3 % of the original Guinney- and 100.0 % of FIRE-3 population. In XELAVIRI, CMS subgroups were predicted as follows: CMS1: n = 62 (18.4 %); CMS2: n = 174 (51.6 %); CMS3: n = 9 (2.7 %); CMS4: n = 92 (27.3 %). A general prognostic impact of CMS was not observed when all patients were analysed. In RAS/BRAF WT mCRC patients, substantial benefit of COMB versus SEQ treatment was shown for OS and PFS in CMS2 and CMS4, but not in CMS1. Conversely, OS was significantly longer for COMB treatment in patients with RAS MUT and CMS1 mCRC, while SEQ treatment was not inferior in RAS MUT and CMS2 or CMS4 subgroups (see TABLE). Additional data for overall response rates, early tumor shrinkage and sidedness might be presented at the meeting. Conclusions: This retrospective analysis of XELAVIRI suggests that CMS may serve as biomarker that predicts response to initially combined versus less intensive sequential chemotherapy in patients with RAS/BRAF WT mCRC.[Table: see text]

Im Jahr 2011 wurde in den Landkreisen Landshut und Dingolfing erstmals eine spezialisierte ambulante Palliativversorgung (SAPV) eingefuhrt. Vier Jahre nach Einfuhrung sollten Zusammenarbeit, Akzeptanz und Bedarf an speziellen palliativmedizinischen Masnahmen und Fortbildungen aus hausarztlicher Perspektive mittels Fragebogen eruiert werden. Von 01–03/2015 wurden 198 Hausarzte in den Landkreisen Landshut und Dingolfing per Fragebogen kontaktiert. Die Fragenbogen enthielten 16 Fragen aus funf Themengebieten, erstellt auf Basis praktischer Erfahrungen der Autoren und fruheren Arbeiten aus der Literatur. Der Versand erfolgte per Post mit frankiertem und adressiertem Ruckumschlag. Von 198 Hausarzten wurden 40 Bogen zuruckgesandt. 33 % waren weiblich, 53 % mannlich. 85 % hatten mit einem SAPV-Team kooperiert. 23 % besasen die Basisweiterbildung fur Palliativmedizin, 10 % planten, die Zusatzbezeichnung fur Palliativmedizin zu erwerben. Fur 10 % war die Mitarbeit in einem SAPV-Team vorstellbar. 75 % der Befragten gaben an, dass durch die SAPV Krankenhausaufenthalte vermieden werden konnten, und 73 % sahen fur ihre Praxis Einsparungen von Kosten und Zeit. Der uberwiegende Teil der Hausarzte war mit der Arbeit der SAPV und der Kooperation zufrieden. 60 % hielten eine zusatzliche palliativmedizinische Betreuung fur geriatrische Patienten fur sinnvoll. Kritikpunkt war insbesondere die haufig zu spat erfolgte Information uber die Aufnahme eines Patienten in die SAPV. Die aktuelle Umfrage zeigt, dass die Hausarzte den palliativmedizinischen Bedarf ihrer Patienten anerkennen und mehrheitlich die Mitwirkung der SAPV begrusen. Fur eine erfolgreiche Zusammenarbeit sind enge Kooperation und Kommunikation zwischen „Generalisten“ und „Spezialisten fur Palliativmedizin“ notwendig.