Sylvie Lorenzen1, Peter Thuss-Patience2, Claudia Pauligk3, Eray Gökkurt4, Thomas Ettrich5, Florian Lordick6, Michael Stahl7, Peter Reichardt8, Martin Sökler9, Daniel Pink10, Stefan Probst11, Axel Hinke12, Thorsten O Goetze13, Salah E Al-Batran13. 1. Klinikum Rechts der Isar, Technische Universität München, III. Medizinische Klinik und Poliklinik, München, Germany. Electronic address: sylvielorenzen@gmx.de. 2. Charité - Universitätsmedizin Berlin/Campus Virchow Klinikum (CVK), Med. Klinik M. S. Hämatologie, Onkologie und Tumorimmunologie (CC14), Berlin, Germany. 3. Institut für Klinische Krebsforschung IKF GmbH am Krankenhaus Nordwest, Frankfurt, Germany. 4. Hämatologisch-Onkologische Praxis Eppendorf (HOPE), Facharztzentrum Eppendorf, Hamburg, Germany. 5. Universitätsklinikum Ulm, Klinik für Innere Medizin I, Ulm, Germany. 6. Department of Oncology, Gastroenterology, Hepatology, Pulmonology, and Infectious Diseases, University Cancer Center Leipzig (UCCL), Leipzig University Medical Center, Leipzig, Germany. 7. Evang. Kliniken Essen-Mitte, Klinik für Internistische Onkologie und Hämatologie, Essen, Germany. 8. HELIOS Klinikum Berlin Buch, Klinik für Interdisziplinäre Onkologie, Sarkomzentrum Berlin-Brandenburg, Berlin, Germany. 9. Universitätsklinikum Tübingen, Medizinische Klinik II, Tübingen, Germany. 10. Klinik und Poliklinik für Innere Medizin C, Hämatologie und Onkologie, Transplantationszentrum, Palliativmedizin, Universität Greifswald, Greifswald, Germany; Klinik für Hämatologie, Onkologie und Palliativmedizin, Sarkomzentrum Berlin-Brandenburg, HELIOS Klinikum Bad-Saarow, Bad Saarow, Germany. 11. Klinikum Bielefeld Mitte, Klinik für Hämatologie, Onkologie U. Palliativmedizin, Bielefeld, Germany. 12. CCRC Cancer Clinical Research Consulting, Düsseldorf, Germany. 13. Institut für Klinische Krebsforschung IKF GmbH am Krankenhaus Nordwest, Frankfurt, Germany; Krankenhaus Nordwest, Frankfurt, Germany.
Abstract
BACKGROUND: Ramucirumab and paclitaxel is the standard second-line therapy in patients with metastatic gastroesophageal adenocarcinoma. We report the efficacy and safety analyses of FOLFIRI and ramucirumab versus paclitaxel and ramucirumab after the failure of a platinum- and fluoropyrimidine-containing chemotherapy. METHODS: This multicenter, investigator initiated, phase II trial randomised patients with gastroesophageal adenocarcinoma to either FOLFIRI plus ramucirumab (RAM) (arm A) or paclitaxel plus RAM (arm B). The primary end-point was 6-month overall survival (OS) rate, with a proportion of ≥65% in arm A considered a positive signal for further investigation. RESULTS: 111 patients (65% of patients had prior docetaxel) were enrolled and 110 patients qualified for ITT population (arm A, 72; arm B, 38). The study did not meet the primary end-point for the comparison with historical control, as 6-month OS rate in the FOLFIRI plus RAM arm was 54% (95% CI 44-67). In between arm comparison, OS was similar (hazard ratio, HR 0.97 [95% CI 0.62-1.52]), while objective response rates (ORRs) and PFS were numerically better in arm A versus arm B (HR for PFS 0.73; ORR, 22% versus 11%). These differences were largely attributed to favourable efficacy results for arm A in docetaxel-pretreated patients (HR, 0.49; ORR, 25% versus 8%). In the safety population (n = 106), grade 3-5 adverse events were similar between arms (arm A, 75%; arm B, 68%). CONCLUSION: The RAMIRIS trial demonstrated feasibility of FOLFIRI plus RAM. While the study was formally negative, it provided a signal to further investigate this combination for the group of patients with previous docetaxel therapy. TRIAL REGISTRATION: clinicaltrials.gov identifier: NCT03081143.
BACKGROUND: Ramucirumab and paclitaxel is the standard second-line therapy in patients with metastatic gastroesophageal adenocarcinoma. We report the efficacy and safety analyses of FOLFIRI and ramucirumab versus paclitaxel and ramucirumab after the failure of a platinum- and fluoropyrimidine-containing chemotherapy. METHODS: This multicenter, investigator initiated, phase II trial randomised patients with gastroesophageal adenocarcinoma to either FOLFIRI plus ramucirumab (RAM) (arm A) or paclitaxel plus RAM (arm B). The primary end-point was 6-month overall survival (OS) rate, with a proportion of ≥65% in arm A considered a positive signal for further investigation. RESULTS: 111 patients (65% of patients had prior docetaxel) were enrolled and 110 patients qualified for ITT population (arm A, 72; arm B, 38). The study did not meet the primary end-point for the comparison with historical control, as 6-month OS rate in the FOLFIRI plus RAM arm was 54% (95% CI 44-67). In between arm comparison, OS was similar (hazard ratio, HR 0.97 [95% CI 0.62-1.52]), while objective response rates (ORRs) and PFS were numerically better in arm A versus arm B (HR for PFS 0.73; ORR, 22% versus 11%). These differences were largely attributed to favourable efficacy results for arm A in docetaxel-pretreated patients (HR, 0.49; ORR, 25% versus 8%). In the safety population (n = 106), grade 3-5 adverse events were similar between arms (arm A, 75%; arm B, 68%). CONCLUSION: The RAMIRIS trial demonstrated feasibility of FOLFIRI plus RAM. While the study was formally negative, it provided a signal to further investigate this combination for the group of patients with previous docetaxel therapy. TRIAL REGISTRATION: clinicaltrials.gov identifier: NCT03081143.