Factors That Influence Conversion to Resectability and Survival After Resection of Metastases in RAS WT Metastatic Colorectal Cancer (mCRC): Analysis of FIRE-3- AIOKRK0306

Annals of Surgical Oncology, vol. 27, pp. 2389–2401

Abstract

BACKGROUND: Tumor assessments after first-line therapy of RAS wild-type mCRC with cetuximab (cet) versus bevacizumab (bev) in combination with FOLFIRI were evaluated for factors influencing resectability, conversion to resectability, and survival after best response. METHODS: Conversion to resectability was defined as conversion of initially unresectable to resectable disease at best response as determined by retrospective assessment. Univariate and multivariate logistic models were fitted with resectability at best response as response variable. A Cox model comparing the survival from best response was used to measure the influence of treatment, resectability at best response, and resection. Interaction of resection and treatment arm on survival was tested by likelihood ratio test. RESULTS: Overall, 270 patients were evaluable (127 cet-arm, 143 bev-arm). Lung metastases (odds ratio [OR] 0.35, 95% confidence response [CI] 0.19-0.63), BRAF mutation (OR 0.33, 95% CI 0.12-0.82), and elevated alkaline phosphatase (OR 0.42, 95% CI 0.18-0.9) before randomization were associated with less chance of successful conversion and were integrated into a nomogram. Early tumor shrinkage (OR 1.86, 95% CI 1.06-3.3; p 0.034) and depth of response (OR 1.02, 95% CI 1.01-1.03; p < 0.001) were associated with successful conversion therapy. Resection of metastases improved post-best-response survival (hazard ratio 0.53, 95% CI 0.29-0.97; p = 0.039), predominantely in cet-treated patients (interaction test, p = 0.02). CONCLUSIONS: Conversion to resectability is significantly associated with baseline characteristics that can be used in a nomogram to predict conversion. Moreover, early efficacy parameters (ETS and DpR) are associated with successful conversion therapy. In FIRE-3, resection of metastases was associated with improved post-best response survival, this effect originated predominantly from the cetuximab-based study arm.

Authors 19

1. Dominik Paul Modest corresponding

   Charité - Universitätsmedizin Berlin

   Affiliation as printed

   Department of Hematology, Oncology and Tumor Immunology, CVK, Charité Universitätsmedizin Berlin, Berlin, Germany. dominik.modest@med.uni-muenchen.de

   Department of Hematology, Oncology and Tumor Immunology, CVK, Charité Universitätsmedizin Berlin, Berlin, Germany

2. Volker Heinemann

   Ludwig-Maximilians-Universität München · LMU Klinikum

   Affiliation as printed

   Medical Department III and Comprehensive Cancer Center, Hospital of the University, Ludwig-Maximilian-University (LMU), Munich, Germany

3. Gunnar Folprecht

   University Hospital Carl Gustav Carus

   Affiliation as printed

   University Cancer Center/Medical Department I, University Hospital Carl Gustav Carus, Dresden, Germany

4. Timm Denecke

   Charité - Universitätsmedizin Berlin

   Affiliation as printed

   Institute of Radiology, Charité, Berlin, Germany

5. Johann Pratschke

   Charité - Universitätsmedizin Berlin

   Affiliation as printed

   General, Visceral, and Transplantation Surgery, Charité - Universitätsmedizin Berlin, Berlin, Germany

6. Hauke Lang

   Johannes Gutenberg University Mainz · University Medical Center of the Johannes Gutenberg University Mainz

   Affiliation as printed

   Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Universitätsmedizin Mainz, Mainz, Germany

7. Marc H.A. Bemelmans

   Maastricht University Medical Centre

   Affiliation as printed

   Department of Surgery, Maastricht University Medical Centre, Maastricht, The Netherlands

8. Thomas Becker

   University Hospital Schleswig-Holstein

   Affiliation as printed

   Klinik für Allgemeine-, Viszeral-, Thorax-, Transplantations- und Kinderchirurgie, Universitätsklinikum Schleswig-Holstein, Campus Kiel, Kiel, Germany

9. Markus Rentsch

   Ludwig-Maximilians-Universität München

   Affiliation as printed

   Department of General, Visceral, Transplantation, Vascular and Thoracic Surgery, Hospital of the University of Munich, Munich, Germany

10. Daniel Seehofer

    University Hospital Leipzig · Leipzig University

    Affiliation as printed

    Klinik und Poliklinik für Visceral-, Transplantations-, Thorax- und Gefäßchirurgie Universitätsklinikum Leipzig, Leipzig, Germany

11. Christiane J. Bruns

    University Hospital Cologne

    Affiliation as printed

    Klinik und Poliklinik für Allgemein-, Viszeral- und Tumorchirurgie, Universitätsklinikum Köln, Cologne, Germany

12. Bernhard Gebauer

    Charité - Universitätsmedizin Berlin

    Affiliation as printed

    Institute of Radiology, Charité, Berlin, Germany

13. Swantje Held

    ClinAssess (Germany)

    Affiliation as printed

    ClinAssess GmbH, Leverkusen, Germany

14. Arndt Stahler

    Ludwig-Maximilians-Universität München · LMU Klinikum

    Affiliation as printed

    Medical Department III and Comprehensive Cancer Center, Hospital of the University, Ludwig-Maximilian-University (LMU), Munich, Germany

15. Kathrin S. Heinrich

    Ludwig-Maximilians-Universität München · LMU Klinikum

    Affiliation as printed

    Medical Department III and Comprehensive Cancer Center, Hospital of the University, Ludwig-Maximilian-University (LMU), Munich, Germany

16. Jobst Christian von Einem

    Charité - Universitätsmedizin Berlin

    Affiliation as printed

    Department of Hematology, Oncology and Tumor Immunology, CVK, Charité Universitätsmedizin Berlin, Berlin, Germany

17. Sebastian Stintzing

    Charité - Universitätsmedizin Berlin

    Affiliation as printed

    Department of Hematology, Oncology and Tumor Immunology, CVK, Charité Universitätsmedizin Berlin, Berlin, Germany

18. Ulf P. Neumann Aachen Department of General, Visceral and Transplantation Surgery

    Universitätsklinikum Aachen · Maastricht University Medical Centre

    Affiliation as printed

    Department of General, Visceral and Transplantation Surgery, University Hospital Aachen, Aachen, Germany

    Department of Surgery, Maastricht University Medical Centre, Maastricht, The Netherlands

19. Ingrid Ricard

    Ludwig-Maximilians-Universität München · LMU Klinikum

    Affiliation as printed

    Comprehensive Cancer Center, Hospital of the University, Ludwig-Maximilian-University (LMU), Munich, Germany