Panitumumab Plus Fluorouracil and Folinic Acid Versus Fluorouracil and Folinic Acid Alone as Maintenance Therapy in RAS Wild-Type Metastatic Colorectal Cancer: The Randomized PANAMA Trial (AIO KRK 0212)

Author(s): Dominik Paul Modest, MD1,2; Meinolf Karthaus, MD3; Stefan Fruehauf, MD4; Ullrich Graeven, MD5; Lothar Müller, MD6; Alexander Otto König, MD7; Ludwig Fischer von Weikersthal, MD8; Karel Caca9, Albrecht Kretzschmar, MD10; Eray Goekkurt, MD11,12; Siegfried Haas, MD13; Annika Kurreck, MD1; Arndt Stahler, MD1; Swantje Held, MSc15; Armin Jarosch, MD15; David Horst, MD2,15; Anke Reinacher-Schick, MD16; Stefan Kasper, MD2,17; Volker Heinemann, MD2,18; Sebastian Stintzing, MD1,2; and Tanja Trarbach, MD19
Source: DOI: 10.1200/JCO.21.01332 Journal of Clinical Oncology 40, no. 1 (January 01, 2022) 72-82. Published online September 17, 2021. PMID: 34533973
Lucio Gordan MD

Dr. Gordan's Thoughts

PFS difference is small. But argument can be made for a younger patient who desires aggressive therapy and toxicities have been manageable.

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.


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 (NCT01991873).


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%).


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.

Author Affiliations

1Department of Hematology, Oncology and Tumorimmunology, Charité-Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany 2German Cancer Consortium (DKTK), German Cancer Research Centre (DKFZ), Heidelberg, Germany 3Department of Hematology and Oncology, Munich Hospital Neuperlach, Munich, Germany 4Dr Hancken Hospital, Stade, Germany 5Kliniken Maria Hilf GmbH, Mönchengladbach, Germany 6Oncology Practice UnterEms, Leer, Germany 7Department of Gastroenterology, University Medicine Göttingen, Göttingen, Germany 8Gesundheitszentrum St Marien, Amberg, Germany 9Department of Gastroenterology, Hematology and Oncology, Hospital Ludwigsburg, Ludwigsburg, Germany 10MVZ Mitte, Leipzig, Germany 11Practice of Hematology and Oncology (HOPE), Hamburg, Germany 12University Cancer Center Hamburg (UCCH), Hamburg, Germany 13Department of Hematology and Oncology, Friedrich-Ebert-Hospital, Neumünster, Germany 14ClinAssess GmbH, Leverkusen, Germany 15Charité Universitätsmedizin, Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Institute of Pathology, Berlin, Germany 16St Joseph Hospital, Bochum, Germany 17Department of Medical Oncology, West German Cancer Center, Westdeutsches Tumorzentrum, University Hospital of Essen, Essen, Germany 18Department of Medicine III and Comprehensive Cancer Center, University Hospital (LMU), Munich, Germany 19Zentrum für Tumorbiologie und Integrative Medizin, Klinikum Wilhelmshaven, Wilhelmshaven, Germany

1 thought on “Panitumumab Plus Fluorouracil and Folinic Acid Versus Fluorouracil and Folinic Acid Alone as Maintenance Therapy in RAS Wild-Type Metastatic Colorectal Cancer: The Randomized PANAMA Trial (AIO KRK 0212)”

  1. I understand toxicity is greater with with FU/FA plus Pmab and I will question where we will find the space to use it once the routine use of Bev. is the standard in my view.

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