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H. Riess,

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*-002 -. H. Riess,

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H. Riess,

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  1. 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*-002 - 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 *CHARITÉONKOLOGIE: Clinical studies in GI cancers

  2. CONKO-002 Study rationale • 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 • Low Toxicity • grade III + IV: 19/143 cycles (13%) • The phase III study was designed to evaluate GFF efficacy as compared to GEM standard treatment. *Oettle et al, Ann Oncol, 11: 1267-72

  3. Stratification: KPS (60-80 % vs. 90-100 %) Tumor stage (III vs. IVa vs. IVb) GEM: 1000 mg/m2/wk 5-FU: 750 mg/m2/wk FA: 200 mg/m2/wk CONKO-002 GFF vs. GEM study design x 4 wks, q 6 wks Centralized Randomisation • GEM: • 1000 mg/m2/wk x 7 wks 1000 mg/m2/wk x 3 wks, q 4 wks

  4. CONKO-002 Study endpoints • Primary: • Overall survival (mOS) • Secondary: • Time to tumor progression (TTP) • Toxicity • Quality of Life (not yet analysed)

  5. CONKO-002 Statistical considerations • Hypothesis: 33% improvement in median survival • Expected median OS: • GEM arm: 6 months • GFF arm: 8 months • Statistics: • Kaplan-Meier estimates and two-tailed log-rank test with significance level of 0.05 and a power of 80% • 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. CONKO-002 Inclusion criteria • Histologically or cytologically proven locally advanced or metastatic, inoperable pancreatic carcinoma • Measurable disease • Karnofsky performance status  60% • No prior chemo- or radiotherapy • Adequate hematologic, renal and hepatic function • Written informed consent

  7. CONKO-002 Patient disposition Randomized patientsn=473 • Time of recruitment: 08/00 - 11/03 • Final data-cut: 11/04 • recruiting centres: 98 • deaths observed at data-cut: 451 (95.3 %) • median time on study: 18.2 months (for patients living at data-cut) Non-eligible patients: • 3 pts. with other tumors (2 ovarial-ca, 1 colon-ca) • 2 pts. after surgical resection without recurrent disease • 1 pt. with MTX comedication • 1 pt. without histologically confirmed diagnosis GFF235 pts. GEM238 pts. Evaluable patientsn=466 GFF230 pts. GEM236 pts.

  8. CONKO-002Results

  9. CONKO-002 Patients` characteristics

  10. CONKO-002 Second-line therapies 39% 29% 42% 27%

  11. 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. 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 = 0.4360

  13. 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 = 0.6830

  14. CONKO-002 Subgroup analysis for overall survival: stage IVb patients KPS = 60-80 KPS = 90-100 mOS GFF: 3.35 months [ 2.4; 4.8] GEM: 4.9 months [3.1; 5.7] mOS GFF: 8.5 months [7.3; 11.2] GEM: 6.2 months [5.4; 9.3] days days Log rank: p = 0.6153 Log rank: p = 0.1719

  15. CONKO-002 Toxicities

  16. CONKO-002 Summary • Acceptable toxicities in both arms • No difference in response rate • No difference in time to tumor progression • No difference in overall survival • Trend towards better survival with combination therapy for patients with good KPS 90-100% • Weak trend towards better survival with standard gemcitabine therapy for patients with KPS 60-80%

  17. CONKO-002 Conclusions • The combination of gemcitabine, 5-FU and folinic acid did not result in improved survival as compared to gemcitabine standard therapy • Single agent gemcitabine remains the standard of care for patients with advanced pancreatic cancer

  18. CONKO-002Top recruiting centres (>6 pts.) • Charité, Universitätsmedizin Berlin, Campus Virchow-Klinikum - Germany • Klinikum Mannheim gGmbH, Universitätsklinikum, Fakultät für Klinische Medizin Mannheim - Germany • 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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