Florian Kron

Zusammenfassung: Hintergrund Seit 2009 führen zielgerichtete Therapien gegen molekulare Tumoreigenschaften des nichtkleinzelligen Lungenkarzinoms zu signifikanten Verbesserungen des Gesamtüberlebens. Aktuelle Erhebungen der Testraten der dafür obligaten molekularpathologischen Diagnostik zeigen hingegen niedrige Quoten auf. Während im ambulanten Sektor eine Abrechnungsmöglichkeit für die molekulare Diagnostik besteht, wird die fehlende Vergütung im stationären Fallpauschalensystem als Hürde diskutiert. Methode Ziel der Analyse war, die Versorgungs- und Vergütungsstrukturen der molekularen Diagnostik in Deutschland zu erheben. Hierzu wurden der Versorgungspfad und die Abrechnungsmöglichkeiten der molekularen Diagnostik systematisch und qualitativ aufgearbeitet. Im Deutschen Krankenhausverzeichnis wurden quantitativ alle Krankenhäuser erhoben, die Patienten/-innen mit der ICD-10 Diagnose „Lungenkrebs“ behandeln. Diesen Krankenhäusern wurden die zutreffenden ambulanten Abrechnungsmöglichkeiten zugeordnet. Ergebnisse Eine ambulante Abrechnungsmöglichkeit für die molekulare Diagnostik wurde über eine Teilnahme an der vertragsärztlichen Versorgung inklusive medizinischer Versorgungszentren, der ambulanten Behandlung am Krankenhaus, der ambulanten spezialfachärztlichen Versorgung, eine Hochschulambulanz oder eine Teilnahme an einem Vertrag der Besonderen Versorgung definiert. An 1.001 Krankenhausstandorten (889 Krankenhäuser) wurden im Jahr 2020 Lungenkrebspatienten/-innen behandelt. 52% der Krankenhäuser haben keine ambulante Abrechnungsmöglichkeit (n=462), wovon 89%≤500 Betten (n=413) aufweisen. Von 171.824 Krankenhausfällen wurden 32% (n=55.826) in Krankenhäusern ohne ambulante Abrechnungsmöglichkeit behandelt, davon entfielen 81% auf Krankenhäuser≤500 Betten (n=45.260). Schlussfolgerung Krankenhäuser ohne ambulante Abrechnungsmöglichkeit der molekularen Diagnostik könnten aufgrund der nicht kostendeckenden stationären Vergütung einem ökonomischen Fehlanreiz unterliegen. Innovative Versorgungskonzepte zeigen Möglichkeiten einer qualitätsgesicherten, sektorenunabhängigen Vergütung auf. Ein Transfer in die Regelversorgung könnte die Fehlanreize beheben.

Background: In the past decades, highly innovative treatments in the field of diffuse large B-cell lymphoma (DLBCL) became available in clinical practice. The aim of this study was to assess the cost–benefit relation of third-line interventions in DLBCL from a German payer perspective. Methods: Clinical benefit of allogeneic stem cell transplantation (alloSCT), chimeric antigen receptor T cells therapy (CAR T) [tisagenlecleucel (tisa-cel) and axicabtagene ciloleucel (axi-cel)] and best supportive care (BSC) was assessed in terms of median overall survival (median OS) derived from a systematic literature review in PubMed. Real-world treatment costs were retrieved from the university hospitals Cologne and Hamburg-Eppendorf. The cost–benefit relation was analysed using the efficiency frontier concept. Results: Median OS varied from 6.3 months in BSC to 23.5 months in CAR T (axi-cel), while median real-world treatment costs ranged likewise widely from €26,918 in BSC to €340,458 in CAR T (axi-cel). Shown by the efficiency frontier, alloSCT and axi-cel were found as most efficient interventions. Conclusion: The efficiency frontier supports the pricing of innovative therapies, such as third-line interventions in DLBCL, in relation to appropriate comparators. Yet, studies with longer follow-up periods are needed to include studies with unreached median OS and to reflect experiences gained with CAR T in clinical practice.

Zusammenfassung Hintergrund Kaum ein anderes Thema hat in den vergangenen Jahren in onkologischen Fachkreisen für so viel Aufsehen gesorgt wie die CAR-T-Zell-Therapie (CAR chimärer Antigenrezeptor) – sie eröffnet einerseits vollkommen neue Behandlungsmöglichkeiten für Krebspatienten, kostet andererseits jedoch etwa 300.000 € pro Behandlung. Ziel der Arbeit In diesem Beitrag werden ökonomische, prozessuale und organisatorische Herausforderungen der CAR-T-Zell-Therapie analysiert. Dabei wird sowohl die Perspektive der Leistungserbringer und Kostenträger als auch die Sicht der pharmazeutischen Hersteller berücksichtigt. Material und Methoden Zur Auswertung der aktuellen Vergütungssituation wurden unter anderem der aktuelle Fallpauschalenkatalog (Diagnosis-Related-Groups[DRG]-Katalog), Beschlüsse des Gemeinsamen Bundesausschusses (G-BA) und Codierleitlinien herangezogen. Infrastrukturelle Besonderheiten und Prozessthemen basieren auf Erfahrungswerten aus dem Praxisalltag. Ergebnisse Die Analyse zeigt erhebliche ökonomische und prozessuale Herausforderungen insbesondere für die CAR-T-Zell-Zentren. Zusätzliche mit der Produktion in direktem Zusammenhang stehende Aufwendungen werden nicht adäquat vergütet. Erhebliche Qualitäts- und Qualifizierungsaufwände für Krankenhäuser führen zu einem budgetären Druck auf die Zentren. Schlussfolgerung Die hohen Kosten der CAR-T-Zell-Therapie erfordern eine klare und transparente Definition der Abrechnungs- und Vergütungsregeln. Durch die hohe Interaktionsnotwendigkeit im Zentrum und mit dem pharmazeutischen Hersteller entstehen Mehraufwendungen, die das System nicht kostendeckend abbildet.

Introduction: The treatment of cancer patients in Germany is characterized by sectoral separation of the in- and outpatient care accompanied by 2 separate reimbursement systems. By introducing the Guideline of Outpatient Medical Specialist Care in accordance with §116b SGB V (ASV) in 2014, the German legislation empowers office-based physicians and hospitals to jointly provide medical care in the ambulatory setting. Methods: A 1-year period each before and after the introduction of ASV was compared by means of data from the Center for Integrated Oncology Cologne at the University Hospital of Cologne. Only adults with a reliable diagnosis of gastrointestinal tumor (GIT) were considered. Results: Overall, 1,872 cases were considered in the analysis showing significant (p < 0.001) higher median values of revenues across ICD-subgroups for ASV (EUR 427.46) compared to Ambulatory Treatments in Hospitals (EUR 234.21). The exemplary analysis of revenues in neoplasms of the pancreas shows EUR 173.69 on average which are only invoiceable through ASV: flat rate incl. surcharges (EUR 117.79; 68%), structure lump sum (EUR 29.49; 17%), positron-emission tomography (PET)/CT (EUR 13.53; 18%), and ASV consultation hour (EUR 12.89; 7%). Discussion/Conclusion: ASV leads to significant higher revenues across different ICD-subgroups for patients suffering from severe GIT. The collaboration of hospital and office-based physicians ensures patient-centered care with accumulated expertise and avoidance of double examinations. Thus, the inclusion of additional services in the Uniform Value Scale (invoiceable for ASV) is legitimated and enables cost-covering care for the involved parties.

Objectives Treatment of chronic lymphocytic leukemia (CLL) is currently undergoing dramatic changes. We analyzed economic risks in hospitalized patients with CLL from a management perspective. Methods One hundred and twelve patients with CLL hospitalized in 2013 and 2014 at the University Hospital of Cologne were analyzed. To assess profit margins (PMs) per case, diagnosis‐related group (DRG) reimbursement data were merged with an internal cost accounting scheme depending on age, prognostic factors, and DRG key performance indicators. Results In 112 patients, 284 cases coded by 19 different DRG with strongly fluctuating cost revenue ratios were found with an overall negative PM of €137 147. The DRG R61H was identified as the one most commonly coded (174 cases, 61.3%) with a deficit per case of €814. Subanalysis demonstrated that the payments were not cost covering due to excessive length of stay and staff costs. Significant differences in PM per case concerning age, length of stay and number of operation and procedure key (OPS) codes (P < 0.05) were found. Conclusion In our research‐driven tertiary care hospital, inpatient treatment of patients with CLL is not cost covering. This analysis demonstrates the need for novel care/reimbursement structures in CLL. From a hospital management perspective, cost revenue controlling is crucial to avoid major economic risks.

E18278 Background: Recent success of individualized lung cancer therapy has triggered fundamental changes in clinical research strategies. To date there is a strong focus on early proof of concept trials in genetically preselected, often rare, patient subgroups. From a hospital management perspective, this analysis focuses on the economic burden caused by such trials for advanced lung cancer patients in a German Comprehensive Cancer Center (CCC). Methods: Clinical and economic data from trials for advanced lung cancer (LC), pharma-sponsored trials (PhST) as well as investigator initiated trials (IIT), conducted between 2011 and 2015 at the Center for Integrated Oncology (CIO) Cologne, were analyzed using a profit-center calculation model. Results: 161 patients were enrolled in 27 clinical trials including 2,173 trial visits in total (PhST: 1,319, IIT: 854). We have identified ‘trial visit’ as a key economic parameter determining costs and payments. By comparison of two groups (A ≤ 3; B > 3 patients enrolled) we found negative profit margins of €-1,444 per patient (PP) in A and positive in B (€217). Significant differences were found between PhST and IIT (p = 0.009) concerning the number of visits PP, not, however, with regard to duration of treatment PP. Additionally, subanalysis show structural differences in cost composition by conducting PhST and IIT. Conclusions: The development of individualized, genomically targeted LC therapies goes along with an increase of early phase trials in rare genetic subgroups and, consequently, low patient recruitments. For trials with low patient numbers and IIT, it is difficult to break even with the costs. These observations demonstrate the need for CCC to thoroughly calculate the costs of such trials in order to receive adequate, cost-covering compensation by pharmaceutical companies. They also underline the need for novel structures in public funding for investigator-initiated clinical trials in precision medicine.

9085 Background: The Network Genomic Medicine (NGM) Lung Cancer is a health care provider network offering comprehensive next generation sequencing (NGS)-based multiplex genotyping on a central diagnostics platform in Cologne for inoperable lung cancer patients (pts) in Germany. Methods: The NGS panel used consists of 14 genes and 102 amplicons to cover potentially targetable aberrations. Mutation analyses were run on an Illumina (MySeq) platform, FISH analyses were performed separately. In 2015, we have started the second outcome evaluation for all NGM pts who had received NGS-based molecular diagnostics. In particular, we have focused on pts with activating EGFR mutation (EGFR+), ALK translocation (ALK+), BRAF-V600E mutation (BRAF+), HER2 amplification (HER2+) and ROS1 translocation (ROS1+) and on the outcome of pts treated in clinical trials (ct). Results: From 2013-2015 6210 lung cancer pts (n = 4244 non-squamous NSCLC) were genotyped. Overall survival (OS) is shown for 934 NSCLC pts including 110 pts treated in ct. For 108 EGFR+ pts, the OS of pts treated in ct with different 3^rd generation EGFR-TKIs was 55 months (n = 25) vs 22 months in the control group (n = 83) (p = 0,002; mean OS: 29 months; 95%CI: 36-83 months). For 85 ALK+ pts, the OS of pts treated in ct with next-generation ALK-inhibitor after crizotinib failure was 35 months (n = 19) compared to OS of 23 months for 45 pts treated with crizotinib only and 8 months for 19 pts treated with no ALK inhibitors (p < 0,0001; mean OS: 22 months; 95%CI: 22-33 months). For 32 BRAF+ pts and 11 HER2+ pts, the mean OS was 23 months (95%CI: 12-26 months) and 25 months (95%CI: 15-34 months) (p = 0,022). The mean OS of 13 ROS1+ pts was not reached (95%CI: 58-100 months). Conclusions: Here we show successful implementation of NGS-based molecular diagnostics in clinical routine use. Moreover, molecular diagnostics triggers personalized therapy in – and outside clinical trials and improves survival for EGFR+, ALK+, ROS1+, BRAF+ and HER2+ pts. In particular, the use of next-gen. inhibitors after failure of first gen. inhibitors in EGFR+ and ALK+ pts leads to a significant and substantial additional survival benefit.

9018 Background: KRAS mutations in non-small cell lung cancer (NSCLC) still remain therapeutically untargetable. Assuming that these mutations are not mutually exclusive with other driver aberrations, we set out this study in order to describe and analyze co-occurring mutations and their potential therapeutic impact. In a subset of patients with co-occuring driver mutations, we performed additionally whole-exome sequencing (WES) to define clonal and evolutional status of the mutations. Results were compared with data from The Cancer Genome Atlas' (TCGA) for NSCLC. Methods: In a timeframe of 20 months, 4507 patients of a local screening initiative (Network Genomic Medicine Lung Cancer) were analyzed using next-generation parallel sequencing (NGS). The NGS panel consisted of 102 amplicons and 14 genes: KRAS, PIK3CA, BRAF, EGFR, ERBB2, NRAS, DDR2, TP53, ALK, CTNNB1, MET, AKT1, PTEN and MAP2K1. In subsets of patients, fluorescence in-situ hybridization (FISH) was performed for MET, FGFR1, and HER2 amplification and for RET, ALK and ROS1rearrangements. Clinical parameters, therapy, survival and smoking status were also collected. Results: We identified 1207 patients (26.8%) harboring a KRAS mutation, whereof 1080 patients (89.5%) underwent the complete diagnostic panel. The most common mutation was G12C accounting for 41.2%. In a total of 308 patients (28.8%) additional aberrations could be detected, including MET (prevalence 15.3%), FGFR1 (5.0%) and HER2 (12.7%) amplification and mutations in PIK3CA (3.4%), DDR2 (4.4%), PTEN (1.9%), CTNNB1 (1.7%), BRAF (1.3%) and EGFR (1.4%). Less frequently, mutations within NRAS, AKT1, ALK, MET, and MAP2K1 could be detected. 459 patients (42.9%) had co-occurring TP53mutations.. WES on selected cases confirmed the presence of these mutations. Conclusions: To our knowlege our data represent the largest analysis of co-occuring mutations in KRAS- mutated NSCLC. They show that KRAS-mutated NSCLC represents a heterogenous group of tumors with a substantial portion harboring a wide spectrum of additional targetable mutations. Further studies will show whether these findings translate into new therapeutic options in KRAS-mutated NSCLC.