Dominik Paul Modest1,2, Meinolf Karthaus3, Stefan Fruehauf4, Ullrich Graeven5, Lothar Müller6, Alexander Otto König7, Ludwig Fischer von Weikersthal8, Karel Caca9, Albrecht Kretzschmar10, Eray Goekkurt11,12, Siegfried Haas13, Annika Kurreck1, Arndt Stahler1, Swantje Held14, Armin Jarosch14, David Horst2,14, Anke Reinacher-Schick15, Stefan Kasper2,16, Volker Heinemann2,17, Sebastian Stintzing1,2, Tanja Trarbach18. 1. Department of Hematology, Oncology and Tumorimmunology, Charité-Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany. 2. German Cancer Consortium (DKTK), German Cancer Research Centre (DKFZ), Heidelberg, Germany. 3. Department of Hematology and Oncology, Munich Hospital Neuperlach, Munich, Germany. 4. Dr Hancken Hospital, Stade, Germany. 5. Kliniken Maria Hilf GmbH, Mönchengladbach, Germany. 6. Oncology Practice UnterEms, Leer, Germany. 7. Department of Gastroenterology, University Medicine Göttingen, Göttingen, Germany. 8. Gesundheitszentrum St Marien, Amberg, Germany. 9. Department of Gastroenterology, Hematology and Oncology, Hospital Ludwigsburg, Ludwigsburg, Germany. 10. MVZ Mitte, Leipzig, Germany. 11. Practice of Hematology and Oncology (HOPE), Hamburg, Germany. 12. University Cancer Center Hamburg (UCCH), Hamburg, Germany. 13. Department of Hematology and Oncology, Friedrich-Ebert-Hospital, Neumünster, Germany. 14. Charité Universitätsmedizin, Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Institute of Pathology, Berlin, Germany. 15. St Joseph Hospital, Bochum, Germany. 16. Department of Medical Oncology, West German Cancer Center, Westdeutsches Tumorzentrum, University Hospital of Essen, Essen, Germany. 17. Department of Medicine III and Comprehensive Cancer Center, University Hospital (LMU), Munich, Germany. 18. Zentrum für Tumorbiologie und Integrative Medizin, Klinikum Wilhelmshaven, Wilhelmshaven, Germany.
Abstract
PURPOSE: The randomized PANAMA trial investigated the efficacy of panitumumab (Pmab) when added to maintenance therapy with fluorouracil and folinic acid (FU/FA) in patients with RAS wild-type metastatic colorectal cancer. METHODS: Following first-line induction therapy with six cycles of FU/FA and oxaliplatin plus Pmab, responding patients (stable disease or partial or complete remission) were randomly assigned (1:1, open-label) to maintenance treatment with either FU/FA plus Pmab or FU/FA alone. The primary objective was to demonstrate superiority of progression-free survival (PFS, time from random assignment until progression or death) in favor of FU/FA plus Pmab with a hazard ratio (HR) of 0.75, a power of 80%, and a significance level of 10%. Secondary end points included overall survival, objective response rate of maintenance therapy, and toxicity. Survival end points were analyzed by the Kaplan-Meier method and compared by log-rank test and Cox regressions. Dichotomous variables were compared by Fisher's exact test; odds ratios were indicated when appropriate. The trial is registered with ClinicalTrials.gov (NCT01991873). RESULTS: Overall, 248 patients were randomly assigned and received maintenance therapy with either FU/FA plus Pmab (125 patients) or FU/FA alone (123 patients). At data cutoff, with 218 events (of 218 needed), PFS of maintenance therapy was significantly improved with FU/FA plus Pmab (8.8 months v 5.7 months; HR, 0.72; 80% CI, 0.60 to 0.85; P = .014). Overall survival (event rate 54%) numerically favored the FU/FA plus Pmab arm (28.7 months v 25.7 months; HR, 0.84; 95% CI, 0.60 to 1.18; P = .32). Objective response rates were 40.8% in patients receiving FU/FA plus Pmab versus 26.0% in patients receiving FU/FA alone (odds ratio, 1.96; 95% CI, 1.14 to 3.36; P = .02). The most frequent Common Terminology Criteria for Adverse Event grade ≥ 3 event during maintenance therapy was skin rash (7.2%). CONCLUSION: In RAS wild-type metastatic colorectal cancer, maintenance therapy with FU/FA plus Pmab induced a significantly superior PFS compared with FU/FA alone. If active maintenance therapy is aspired following induction therapy with FU/FA and oxaliplatin plus Pmab, FU/FA plus Pmab appears to be the most favorable option.
PURPOSE: The randomized PANAMA trial investigated the efficacy of panitumumab (Pmab) when added to maintenance therapy with fluorouracil and folinic acid (FU/FA) in patients with RAS wild-type metastatic colorectal cancer. METHODS: Following first-line induction therapy with six cycles of FU/FA and oxaliplatin plus Pmab, responding patients (stable disease or partial or complete remission) were randomly assigned (1:1, open-label) to maintenance treatment with either FU/FA plus Pmab or FU/FA alone. The primary objective was to demonstrate superiority of progression-free survival (PFS, time from random assignment until progression or death) in favor of FU/FA plus Pmab with a hazard ratio (HR) of 0.75, a power of 80%, and a significance level of 10%. Secondary end points included overall survival, objective response rate of maintenance therapy, and toxicity. Survival end points were analyzed by the Kaplan-Meier method and compared by log-rank test and Cox regressions. Dichotomous variables were compared by Fisher's exact test; odds ratios were indicated when appropriate. The trial is registered with ClinicalTrials.gov (NCT01991873). RESULTS: Overall, 248 patients were randomly assigned and received maintenance therapy with either FU/FA plus Pmab (125 patients) or FU/FA alone (123 patients). At data cutoff, with 218 events (of 218 needed), PFS of maintenance therapy was significantly improved with FU/FA plus Pmab (8.8 months v 5.7 months; HR, 0.72; 80% CI, 0.60 to 0.85; P = .014). Overall survival (event rate 54%) numerically favored the FU/FA plus Pmab arm (28.7 months v 25.7 months; HR, 0.84; 95% CI, 0.60 to 1.18; P = .32). Objective response rates were 40.8% in patients receiving FU/FA plus Pmab versus 26.0% in patients receiving FU/FA alone (odds ratio, 1.96; 95% CI, 1.14 to 3.36; P = .02). The most frequent Common Terminology Criteria for Adverse Event grade ≥ 3 event during maintenance therapy was skin rash (7.2%). CONCLUSION: In RAS wild-type metastatic colorectal cancer, maintenance therapy with FU/FA plus Pmab induced a significantly superior PFS compared with FU/FA alone. If active maintenance therapy is aspired following induction therapy with FU/FA and oxaliplatin plus Pmab, FU/FA plus Pmab appears to be the most favorable option.
Authors: Marc Peeters; Timothy Jay Price; Andrés Cervantes; Alberto F Sobrero; Michel Ducreux; Yevhen Hotko; Thierry André; Emily Chan; Florian Lordick; Cornelis J A Punt; Andrew H Strickland; Gregory Wilson; Tudor-Eliade Ciuleanu; Laslo Roman; Eric Van Cutsem; Valentina Tzekova; Simon Collins; Kelly S Oliner; Alan Rong; Jennifer Gansert Journal: J Clin Oncol Date: 2010-10-04 Impact factor: 44.544
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Authors: E Aranda; P García-Alfonso; M Benavides; A Sánchez Ruiz; C Guillén-Ponce; M J Safont; J Alcaide; A Gómez; R López; J L Manzano; M Méndez Ureña; J Sastre; F Rivera; C Grávalos; T García; J I Martín-Valadés; E Falcó; M Navalón; E González Flores; A Ma García Tapiador; A Ma López Muñoz; E Barrajón; M Reboredo; P García Teijido; A Viudez; N Cárdenas; E Díaz-Rubio Journal: Eur J Cancer Date: 2018-07-24 Impact factor: 9.162
Authors: Julian Walter Holch; Ingrid Ricard; Sebastian Stintzing; Dominik Paul Modest; Volker Heinemann Journal: Eur J Cancer Date: 2016-11-29 Impact factor: 9.162
Authors: Sebastian Stintzing; Dominik P Modest; Lisa Rossius; Markus M Lerch; Ludwig Fischer von Weikersthal; Thomas Decker; Alexander Kiani; Ursula Vehling-Kaiser; Salah-Eddin Al-Batran; Tobias Heintges; Christian Lerchenmüller; Christoph Kahl; Gernot Seipelt; Frank Kullmann; Martina Stauch; Werner Scheithauer; Swantje Held; Clemens Giessen-Jung; Markus Moehler; Andreas Jagenburg; Thomas Kirchner; Andreas Jung; Volker Heinemann Journal: Lancet Oncol Date: 2016-08-27 Impact factor: 41.316
Authors: Eric Van Cutsem; Claus-Henning Köhne; Erika Hitre; Jerzy Zaluski; Chung-Rong Chang Chien; Anatoly Makhson; Geert D'Haens; Tamás Pintér; Robert Lim; György Bodoky; Jae Kyung Roh; Gunnar Folprecht; Paul Ruff; Christopher Stroh; Sabine Tejpar; Michael Schlichting; Johannes Nippgen; Philippe Rougier Journal: N Engl J Med Date: 2009-04-02 Impact factor: 91.245
Authors: A Kurreck; M Geissler; U M Martens; J Riera-Knorrenschild; J Greeve; A Florschütz; S Wessendorf; T Ettrich; S Kanzler; D Nörenberg; M Seidensticker; S Held; P Buechner-Steudel; J Atzpodien; V Heinemann; S Stintzing; T Seufferlein; A Tannapfel; A C Reinacher-Schick; D P Modest Journal: J Cancer Res Clin Oncol Date: 2020-05-24 Impact factor: 4.553