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Charité - Universitätsmedizin Berlin - Campus Virchow-Klinikum Phase III Study: Gemcitabine and 5-FU (24h infusion) with Folinic acid (GFF) vs. Gemcitabine.

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Präsentation zum Thema: "Charité - Universitätsmedizin Berlin - Campus Virchow-Klinikum Phase III Study: Gemcitabine and 5-FU (24h infusion) with Folinic acid (GFF) vs. Gemcitabine."—  Präsentation transkript:

1 Charité - Universitätsmedizin Berlin - Campus Virchow-Klinikum Phase III Study: Gemcitabine and 5-FU (24h infusion) with Folinic acid (GFF) vs. Gemcitabine alone (GEM) in the Treatment of Advanced, Inoperable Pancreatic Cancer - CONKO* H. Riess, A. Helm, M. Niedergethmann, I. Schmidt-Wolf, M. Moik, C Hammer, K. Zippel, K. Weigang-Köhler, M. Stauch, H. Oettle, Deutsche Krebsgesellschaft Charité Virchow Klinikum Berlin, Universitätsklinikum Mannheim, Universitätsklinikum Bonn, Landeskrankenhaus Salzburg, Humaine Klinikum Bad Saarow, Oskar-Ziethen-Krankenhaus Berlin, Klinikum Nürnberg Nord, Outpatient Department Stauch, Kronach Austria; Germany *CHARITÉ ONKOLOGIE: Clinical studies in GI cancers

2 Charité - Universitätsmedizin Berlin - Campus Virchow-Klinikum H. Riess CONKO-002 Study rationale n GFF combination is active in advanced pancreatic carcinoma: phase II study* results (38 pts.) RR: 5.2% Median TTP: 7.1 (0.4; 18.1) months Median OS: 9.3 (0.5; 26.5+) months n Low Toxicity grade III + IV: 19/143 cycles (13%) n The phase III study was designed to evaluate GFF efficacy as compared to GEM standard treatment. *Oettle et al, Ann Oncol, 11:

3 Charité - Universitätsmedizin Berlin - Campus Virchow-Klinikum H. Riess CONKO-002 GFF vs. GEM study design Stratification: n KPS (60-80 % vs %) n Tumor stage (III vs. IVa vs. IVb) n GEM: 1000 mg/m 2 /wk n 5-FU: 750 mg/m 2 /wk n FA: 200 mg/m 2 /wk Centralized Randomisation n GEM: 1000 mg/m2/wk x 7 wks  1000 mg/m2/wk x 3 wks, q 4 wks x 4 wks, q 6 wks

4 Charité - Universitätsmedizin Berlin - Campus Virchow-Klinikum H. Riess CONKO-002 Study endpoints n Primary: Overall survival (mOS) n Secondary: Time to tumor progression (TTP) Toxicity Quality of Life (not yet analysed)

5 Charité - Universitätsmedizin Berlin - Campus Virchow-Klinikum H. Riess CONKO-002 Statistical considerations n Hypothesis: 33% improvement in median survival Expected median OS: y GEM arm: 6 months y GFF arm: 8 months n Statistics: Kaplan-Meier estimates and two-tailed log-rank test with significance level of 0.05 and a power of 80% n Sample size: 472 pts – 236 pts per treatment arm (1:1 ratio) with up to 20% drop-outs 392 events (deaths) needed for final analysis

6 Charité - Universitätsmedizin Berlin - Campus Virchow-Klinikum H. Riess CONKO-002 Inclusion criteria n Histologically or cytologically proven locally advanced or metastatic, inoperable pancreatic carcinoma n Measurable disease n Karnofsky performance status  60% n No prior chemo- or radiotherapy n Adequate hematologic, renal and hepatic function n Written informed consent

7 Charité - Universitätsmedizin Berlin - Campus Virchow-Klinikum H. Riess CONKO-002 Patient disposition n Time of recruitment: 08/ /03 n Final data-cut: 11/04 n recruiting centres: 98 n deaths observed at data-cut: 451 (95.3 %) n median time on study: 18.2 months (for patients living at data-cut) Non-eligible patients: n 3 pts. with other tumors (2 ovarial- ca, 1 colon-ca) n 2 pts. after surgical resection without recurrent disease n 1 pt. with MTX comedication n 1 pt. without histologically confirmed diagnosis Randomized patients n=473 GFF 235 pts. GEM 238 pts. Evaluable patients n=466 GFF 230 pts. GEM 236 pts.

8 Charité - Universitätsmedizin Berlin - Campus Virchow-Klinikum CONKO-002 Results

9 Charité - Universitätsmedizin Berlin - Campus Virchow-Klinikum H. Riess CONKO-002 Patients` characteristics

10 Charité - Universitätsmedizin Berlin - Campus Virchow-Klinikum H. Riess CONKO-002 Second-line therapies 29% 39% 27% 42%

11 Charité - Universitätsmedizin Berlin - Campus Virchow-Klinikum H. Riess CONKO-002 Tumor response rates 315 pts as documented 95 pts died before first staging (12 weeks) – documented as PD 56 pts missing data (GFF: 11.3 %; GEM: 12.7 %)

12 Charité - Universitätsmedizin Berlin - Campus Virchow-Klinikum H. Riess CONKO-002 Time to tumor progression days mTTP GFF: 3.5 months [ 3.0; 4.1] GEM: 3.5 months [3.0; 4.2] Log rank: p =

13 Charité - Universitätsmedizin Berlin - Campus Virchow-Klinikum H. Riess CONKO-002 Overall survival days mOS GFF: 5.85 months [ 5.1; 7.3] GEM: 6.2 months [5.4; 8.0] Log rank: p =

14 Charité - Universitätsmedizin Berlin - Campus Virchow-Klinikum H. Riess CONKO-002 Subgroup analysis for overall survival: stage IVb patients days mOS GFF: 3.35 months [ 2.4; 4.8] GEM: 4.9 months [3.1; 5.7] KPS = KPS = Log rank: p = Log rank: p = mOS GFF: 8.5 months [7.3; 11.2] GEM: 6.2 months [5.4; 9.3]

15 Charité - Universitätsmedizin Berlin - Campus Virchow-Klinikum H. Riess CONKO-002 Toxicities

16 Charité - Universitätsmedizin Berlin - Campus Virchow-Klinikum H. Riess CONKO-002 Summary n Acceptable toxicities in both arms n No difference in response rate n No difference in time to tumor progression n No difference in overall survival n Trend towards better survival with combination therapy for patients with good KPS % n Weak trend towards better survival with standard gemcitabine therapy for patients with KPS 60-80%

17 Charité - Universitätsmedizin Berlin - Campus Virchow-Klinikum H. Riess CONKO-002 Conclusions n The combination of gemcitabine, 5-FU and folinic acid did not result in improved survival as compared to gemcitabine standard therapy n Single agent gemcitabine remains the standard of care for patients with advanced pancreatic cancer

18 Charité - Universitätsmedizin Berlin - Campus Virchow-Klinikum H. Riess CONKO-002 Top recruiting centres (>6 pts.) n Charité, Universitätsmedizin Berlin, Campus Virchow-Klinikum - Germany Klinikum Mannheim gGmbH, Universitätsklinikum, Fakultät für Klinische Medizin Mannheim - Germany n SRH Wald-Klinikum Gera gGmbH - Germany Gemeinnützige Salzburger Landeskliniken Betriebsgesellschaft mbH - Austria Universitätsklinikum Bonn, Medizinische Fakultät der Rheinischen Friedrich-Wilhelms-Universität - Germany Humaine Klinikum Bad Saarow - Germany Paritätisches Krankenhaus Lichtenberg, Oskar-Ziethen-Krankenhaus, Berlin - Germany Praxis Dr. Stauch, Kronach - Germany Klinikum Nürnberg Nord - Germany Praxis Dr. Schlag, Würzburg - Germany Praxis Dr. Müller, Leer - Germany Klinikum Bremen Mitte gGmbH - Germany Marienkrankenhaus Hamburg - Germany Krankenhaus St. Elisabeth u. St. Barbara Halle - Germany Klinikum der Stadt Stralsund Krkh. West - Germany DRK Krankenhaus Luckenwalde - Germany Eberhard-Karls-Universität Tübingen, Universitätsklinikum Tübingen - Germany Kreiskrankenhaus Leer (Ostfriesland) - Germany Katharinenhospital Stuttgart - Germany Katholisches Klinikum Mainz St. Vincenz- und Elisabeth-Hospital - Germany Allgemeines Krankenhaus der Stadt Hagen - Germany Praxis Drs. med. Schimke/Jacobs, Saarbrücken - Germany Klinikum Ernst-von-Bergmann Potsdam - Germany Charité, Universitätsmedizin Berlin, Campus Berlin-Buch - Germany Praxis Dr. Müller-Hagen, Hamburg - Germany Ev. Waldkrankenhaus Spandau, Berlin - Germany Klinikum Neubrandenburg- Germany


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