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DOI: 10.1055/a-1018-1651
Retrospektive GKV-Versorgungsforschungsstudie über GnRH-Antagonisten/-Agonisten zur initialen Therapie des fortgeschrittenen Prostatakarzinoms – Verordnungsmuster und Krankenhauskosten in Deutschland
Retrospective SHI (Statutory Health Insurances) real-world study on initial GnRH antagonist and agonist therapy for advanced prostate cancer: prescription patterns and hospital costs in GermanyPublication History
Publication Date:
19 November 2019 (online)
Zusammenfassung
Hintergrund Die Androgendeprivationstherapie (ADT) ist fester Therapiebestandteil des fortgeschrittenen oder metastasierten Prostatakarzinoms (PCa). Ziel der vorliegenden Versorgungsforschungsstudie war der Vergleich von Verordnungsmustern, Hospitalisierungsraten und Krankenhauskosten beim initialen Einsatz verschiedener GnRH-Agonisten und -Antagonisten (GnRHa).
Material und Methoden Anonymisierte GKV-Daten von > 70 Krankenkassen aus 2010 bis 2015 (n = 4 205 227) wurden analysiert (1 Jahr Vorbeobachtung, 1 Indexquartal mit initialer GnRHa-Verordnung, ≥ 2 Jahre Follow-Up (FU)).
Ergebnisse Die Studienpopulation umfasste 2382 PCa-Patienten im Alter von durchschnittlich 75 Jahren. Leuprorelin (Leu) wurde mit 56,6 % am häufigsten verordnet. Bei erstmaliger GnRHa-Anwendung hatten 70 % aller Patienten keine Lymph- oder Fernmetastasen. Nach der initialen Verordnung wurden bei 11,2 % die GnRHa abgesetzt, bei 17,6 % nach durchschnittlich 457 Tagen (Median: 399 Tage) umgestellt, in der Hybrid (Hyb)-Gruppe durchschnittlich 100 Tage schneller als bei den Agonisten (p = 0,016). Die Prävalenzrangfolge der häufigsten Komorbiditäten war über die Zeit gleichbleibend: Hypertonie, Hyperlipidämie, kardiovaskuläre Erkrankungen (CVD) und Diabetes. Die Hypertonieprävalenz zeigte einen signifikant höheren Anstieg unter Agonisten (16,4 %; vs. Antagonist 6,9 % p = 0,022; vs. Hybride 11,6 % p = 0,006). Bei der CVD gab es hinsichtlich der relativen Wachstumsraten zwischen den 3 zusammengefassten Therapieklassen keine signifikanten Unterschiede. Insgesamt waren 23,9 % aller Patienten nach 3 Jahren FU verstorben. Die Mortalitätsrate war am niedrigsten für Triptorelin (Trp, 22,1 %) und am höchsten für Goserelin (Gos, 29,4 %, n.s.). Im Indexquartal hatten 26,4 % der Patienten mind. einen Krankenhausaufenthalt [min; max: Trp 22,4 %; Gos 30,3 %] mit einer mittleren Krankenhausverweildauer/Patient von 3 Tagen [Trp 2,4; Gos 4,5]. Die jährliche Hospitalisierungsrate lag bei 36,2 – 40,7 %, die mittlere Krankenhausverweildauer im gesamten FU zwischen 17,6 (Trp) und 20,8 (Hyb) Tagen. Die Krankenhauskosten im Indexquartal betrugen ca. 1200 EUR [Trp 988; Gos 1803] und pro FU-Jahr ca. 3000 EUR. In der Trp-Kohorte lagen die Gesamtkosten (Indexquartal + 3 Jahre) mehr als 1000 EUR unter dem Durchschnitt von 9476 EUR [Trp 8116; Leu 9779; n.s.].
Schlussfolgerung Diese GKV-Versorgungsforschungsstudie beschreibt die Anwendung von GnRHa zur initialen Therapie beim fortgeschrittenen PCa in Deutschland und zeigt substanzabhängige Unterschiede in den Verordnungsmustern, Hospitalisierungsraten und Krankenhauskosten.
Abstract
Introduction: Androgen deprivation therapy (ADT) plays a pivotal role in the treatment of advanced or metastasised prostate cancer (PCa). The aim of this health services research was to compare real-world data on the initial use of different GnRH agonists and antagonists (GnRHa) with regard to prescription patterns, hospitalisation rates and costs.
Material and methods: Anonymised claims data from > 70 German health insurance funds between 2010 and 2015 (n = 4 205 227) were analysed (1 year pre-observation period, 1 index quarter with initial GnRHa prescription, ≥ 2 years of follow-up (FU)).
Results: The study population included 2382 PCa patients (mean age 75 years). Leuprolide (Leu) was prescribed most frequently (56.6 %). At initial GnRHa administration, 70 % of patients neither had lymph node nor distant metastases. Around 11.2 % of all patients stopped GnRHa treatment after the first prescription, 17.6 % switched their initial therapy to another substance after a mean of 457 days (median: 399 days); in the hybrid (hyb) group 100 days earlier on average than in the agonist group (p = 0.016). The prevalence ranking of the most common comorbidities was consistent over time: hypertension, hyperlipidaemia, cardiovascular disease (CVD) and diabetes. The prevalence of hypertension increased significantly in the agonist group (16.4 %) compared with the antagonist (6.9 %, p = 0.022) and hyb group (11.6 %, p = 0.006). With regard to CVD, there were no significant differences in the relative growth rate between the 3 combined therapy classes. In total, 23.9 % of all patients died within the 3-year FU. The mortality rate was lowest for triptorelin (Trp, 22.1 %) and highest for goserelin (Gos, 29.4 %, n.s.). In the index quarter, 26.4 % of patients had at least one inpatient hospitalisation [min-max: Trp 22.4 %; Gos 30.3 %], with an average length of hospital stay/patient of 3 days [Trp 2.4; Gos 4.5]. The annual hospitalisation rate was between 36.2 and 40.7 %, the average length of hospital stay in the entire FU was between 17.6 (Trp) and 20.8 days (hyb). The average hospital costs in the index quarter were approx. EUR 1200 [Trp 988; Gos 1803] and per FU year approx. EUR 3000. In the Trp cohort, total costs (index quarter + 3 years) were more than EUR 1000 below the average costs of EUR 9476 [Trp 8116; Leu 9779; n.s.].
Conclusion: This comparative retrospective analysis provides real-world information on initial GnRHa treatment for advanced prostate cancer, revealing differences in treatment patterns, hospitalisation rates and hospital costs in Germany.
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Literatur
- 1 Kaatsch P, Spix C, Katalinic A. et al. Krebs in Deutschland für 2013/2014. Berlin: Robert Koch-Institut und die Gesellschaft der epidemiologischen Krebsregister in Deutschland e. V; 2017
- 2 Wong MC, Goggins WB, Wang HH. et al. Global Incidence and Mortality for Prostate Cancer: Analysis of Temporal Patterns and Trends in 36 Countries. European urology 2016; 70: 862-874
- 3 Mottet N, van den Bergh R, Briers E. Guidelines on prostate cancer. 2018 Available at: https://uroweb.org/guideline/prostate-cancer/
- 4 Hinz SB. Monitoring of treatment for metastatic castration-resistant prostate cancer. Aktuelle Urologie 2017; 48: 225-229
- 5 Huggins C, Hodges CV. Studies on prostatic cancer. I. The effect of castration, of estrogen and androgen injection on serum phosphatases in metastatic carcinoma of the prostate. CA: a cancer journal for clinicians 1972; 22: 232-240
- 6 Cornford P, Bellmunt J, Bolla M. et al. EAU-ESTRO-SIOG Guidelines on Prostate Cancer. Part II: Treatment of Relapsing, Metastatic, and Castration-Resistant Prostate Cancer. European urology 2017; 71: 630-642
- 7 Deutsche Krebsgesellschaft, Deusche Krebshilfe, AWMF. Leitlinienprogrogramm Onkologie: Interdisziplinäre Leitlinie der Qualität S3 zur Früherkennung, Diagnose und Therapie der verschiedenen Stadien des Prostatakarzinoms, Langversion 5.0, AWMF Registernummer: 043/022OL. 2018 https://www.leitlinienprogramm-onkologie.de/leitlinien/prostatakarzinom/ (last accessed on: 26/11/2018)
- 8 Merseburger AS, Hupe MC. An Update on Triptorelin: Current Thinking on Androgen Deprivation Therapy for Prostate Cancer. Advances in therapy 2016; 33: 1072-1093
- 9 Shore ND. Experience with degarelix in the treatment of prostate cancer. Therapeutic advances in urology 2013; 5: 11-24
- 10 Furr BJ, Tucker H. The preclinical development of bicalutamide: pharmacodynamics and mechanism of action. Urology 1996; 47: 13-25 ; discussion 29-32
- 11 Sufrin G, Coffey DS. Flutamide. Mechanism of action of a new nonsteroidal antiandrogen. Investigative urology 1976; 13: 429-434
- 12 Ryan CJ, Smith MR, de Bono JS. et al. Abiraterone in metastatic prostate cancer without previous chemotherapy. The New England journal of medicine 2013; 368: 138-148
- 13 Scher HI, Fizazi K, Saad F. et al. Increased survival with enzalutamide in prostate cancer after chemotherapy. The New England journal of medicine 2012; 367: 1187-1197
- 14 Rydzewska LHM, Burdett S, Vale CL. et al. Adding abiraterone to androgen deprivation therapy in men with metastatic hormone-sensitive prostate cancer: A systematic review and meta-analysis. European journal of cancer (Oxford, England : 1990) 2017; 84: 88-101
- 15 Smith MR, Saad F, Chowdhury S. et al. Apalutamide Treatment and Metastasis-free Survival in Prostate Cancer. The New England journal of medicine 2018;
- 16 Hussain M, Fizazi K, Saad F. et al. Enzalutamide in Men with Nonmetastatic, Castration-Resistant Prostate Cancer. The New England journal of medicine 2018; 378: 2465-2474
- 17 Merseburger AS, Hammerer P, Rozet F. et al. Androgen deprivation therapy in castrate-resistant prostate cancer: how important is GnRH agonist backbone therapy?. World journal of urology 2015; 33: 1079-1085
- 18 Hupe MC, Hammerer P, Ketz M. et al. Retrospective analysis of patients with prostate cancer initiating GnRH agonists/antagonists therapy using a German claims database: epidemiological and patient outcomes. Frontiers in Oncology: Genitourinary Oncology 2018;
- 19 Andersohn F, Walker J. Characteristics and external validity of the German Health Risk Institute (HRI) Database. Pharmacoepidemiology and drug safety 2016; 25: 106-109
- 20 Schulze M, Stiegler H, Thielecke C. et al. Cross-sectional analysis of routine treatment for prostate cancer patients: CAPRIS - a healthcare research project of the IQUO. Der Urologe Ausg A 2014; 53: 865-870
- 21 Bolla M, Van Tienhoven G, Warde P. et al. External irradiation with or without long-term androgen suppression for prostate cancer with high metastatic risk: 10-year results of an EORTC randomised study. The Lancet Oncology 2010; 11: 1066-1073
- 22 Efstathiou JA, Bae K, Shipley WU. et al. Cardiovascular mortality after androgen deprivation therapy for locally advanced prostate cancer: RTOG 85-31. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 2009; 27: 92-99
- 23 Keating NL, O'Malley AJ, Freedland SJ. et al. Diabetes and cardiovascular disease during androgen deprivation therapy: observational study of veterans with prostate cancer. Journal of the National Cancer Institute 2010; 102: 39-46
- 24 Tschope C, Kherad B, Spillmann F. et al. Cardiovascular risk of androgen deprivation therapy for treatment of hormone-dependent prostate cancer : Differences between GnRH antagonists and GnRH agonists. Herz 2016; 41: 697-705
- 25 Merseburger AS, Sedding D, Huter K. Cardiovascular risk patients under androgen deprivation therapy: Lower risk with GnRH antagonists compared to LHRH agonists?. Der Urologe Ausg A 2016; 55: 218-225
- 26 Merseburger A, Bro FalkenbergA, Kornilova OJ. New study suggests patients with advanced prostate cancer on androgen deprivation therapy need more dialogue with health care provider, especially around cardiovascular risk. World journal of urology 2018;
- 27 Scailteux L-M, Vincendeau S, Balusson F. et al. Androgen deprivation therapy and cardiovascular risk: No meaningful difference between GnRH antagonist and agonists-a nationwide population-based cohort study based on 2010–2013 French Health Insurance data. European Journal of Cancer 2017; 77: 99-108
- 28 Varenhorst E, Klaff R, Berglund A. et al. Predictors of early androgen deprivation treatment failure in prostate cancer with bone metastases. Cancer medicine 2016; 5: 407-414
- 29 Heyns CF, Simonin MP, Grosgurin P. et al. Comparative efficacy of triptorelin pamoate and leuprolide acetate in men with advanced prostate cancer. BJU international 2003; 92: 226-231
- 30 Uttley L, Whyte S, Gomersall T. et al. Degarelix for Treating Advanced Hormone-Dependent Prostate Cancer: An Evidence Review Group Perspective of a NICE Single Technology Appraisal. PharmacoEconomics 2017; 35: 717-726
- 31 Shim M, Bang WJ, Oh CY. et al. Effectiveness of three different luteinizing hormone-releasing hormone agonists in the chemical castration of patients with prostate cancer: Goserelin versus triptorelin versus leuprolide. Investigative and clinical urology 2019; 60: 244-250