J W Holch1, I Ricard2, S Stintzing3, L Fischer von Weikersthal4, T Decker5, A Kiani6, U Vehling-Kaiser7, T Heintges8, C Kahl9, F Kullmann10, W Scheithauer11, M Moehler12, I Jelas3, D P Modest3, C B Westphalen3, J C von Einem3, M Michl3, V Heinemann3. 1. Department of Internal Medicine III, Comprehensive Cancer Center Munich, University Hospital Grosshadern, Ludwig-Maximilians-Universität München, Marchioninistrasse 15, 81377 Munich, Germany; German Cancer Consortium (DKTK), Partner Site Munich and German Cancer Research Centre (DKFZ), Heidelberg, Germany. Electronic address: Julian.Holch@med.uni-muenchen.de. 2. Institute of Medical Informatics, Biometry, and Epidemiology, Ludwig-Maximilians-Universität München, Marchioninistrasse 15, 81377 Munich, Germany. 3. Department of Internal Medicine III, Comprehensive Cancer Center Munich, University Hospital Grosshadern, Ludwig-Maximilians-Universität München, Marchioninistrasse 15, 81377 Munich, Germany; German Cancer Consortium (DKTK), Partner Site Munich and German Cancer Research Centre (DKFZ), Heidelberg, Germany. 4. Praxis für Onkologie/Haematologie, Gesundheitszentrum St. Marien GmbH, Mariahilfbergweg 7, 92224 Amberg, Germany. 5. Onkologie Ravensburg, Elisabethenstrasse 19, 88212 Ravensburg, Germany. 6. Department of Medicine IV, Klinikum Bayreuth GmbH, Preuschwitzer Strasse 101, 95445 Bayreuth, Germany. 7. Hämato-onkologische Tagesklinik, Dr. Med. Ursula Vehling-Kaiser, Ländgasse 132-135, 84028 Landshut, Germany. 8. Department of Medicine II, Lukaskrankenhaus, Preußenstrasse 84, 41462 Neuss, Germany. 9. Department of Hematology, Oncology and Palliative Care, Klinikum Magdeburg gGmbH, Birkenallee 34, 39130 Magdeburg, Germany. 10. Department of Internal Medicine I, Klinikum Weiden, Söllnerstrasse 16, 92637 Weiden, Germany. 11. Department of Internal Medicine I & CCC, Medical University Vienna, Spitalgasse 23, 1090 Vienna, Austria. 12. University Medical Center Mainz, I. Dept. of Internal Medicine, Langenbeckstrasse 1, 55131 Mainz, Germany.
Abstract
PURPOSE: Increased baseline carcinoembryonic antigen (CEA) serum level is associated with inferior overall survival (OS) in metastatic colorectal cancer (mCRC). However, limited data exist on its predictive relevance for targeted therapies. Therefore, we analysed its relevance in FIRE-3, a randomised phase III study. EXPERIMENTAL DESIGN: FIRE-3 evaluated first-line FOLFIRI plus cetuximab (FOLFIRI/Cet) versus FOLFIRI plus bevacizumab (FOLFIRI/Bev) in mCRC patients with RAS-WT tumour (i.e. wild-type in KRAS and NRAS exons 2-4). Herein, the impact of CEA on patient outcome was investigated. RESULTS:Of 400 patients, 356 (89.0%) were evaluable for CEA. High CEA (>10 ng/ml; N = 237) compared to low CEA (≤10 ng/ml; N = 119) was associated with shorter OS in the FOLFIRI/Bev arm (hazard ratio [HR] = 1.50; P = 0.036), while no significant OS difference was observed in the FOLFIRI/Cet arm (HR = 1.07; P = 0.74). In patients with high CEA, FOLFIRI/Cet compared to FOLFIRI/Bev showed a greater OS benefit (HR = 0.56; P < 0.001) than in patients with low CEA (HR = 0.78; P = 0.30). Furthermore, FOLFIRI/Cet exhibited significantly superior objective response rate in patients with high CEA (odds ratio = 2.21; P = 0.006) in contrast to patients with low CEA (odds ratio = 0.90; P = 0.85). CONCLUSION: In patients with RAS-WT mCRC receiving first-line chemotherapy with FOLFIRI/Cet versus FOLFIRI/Bev, elevated CEA was associated with inferior survival in the bevacizumab arm, while this was not the case when cetuximab was applied. Comparison of OS and objective response rate according to treatment arms indicated that cetuximab was greatly superior to bevacizumab in patients with elevated CEA, while this effect was markedly lower and lost statistical significance in patients with low CEA.
RCT Entities:
PURPOSE: Increased baseline carcinoembryonic antigen (CEA) serum level is associated with inferior overall survival (OS) in metastatic colorectal cancer (mCRC). However, limited data exist on its predictive relevance for targeted therapies. Therefore, we analysed its relevance in FIRE-3, a randomised phase III study. EXPERIMENTAL DESIGN: FIRE-3 evaluated first-line FOLFIRI plus cetuximab (FOLFIRI/Cet) versus FOLFIRI plus bevacizumab (FOLFIRI/Bev) in mCRC patients with RAS-WT tumour (i.e. wild-type in KRAS and NRAS exons 2-4). Herein, the impact of CEA on patient outcome was investigated. RESULTS: Of 400 patients, 356 (89.0%) were evaluable for CEA. High CEA (>10 ng/ml; N = 237) compared to low CEA (≤10 ng/ml; N = 119) was associated with shorter OS in the FOLFIRI/Bev arm (hazard ratio [HR] = 1.50; P = 0.036), while no significant OS difference was observed in the FOLFIRI/Cet arm (HR = 1.07; P = 0.74). In patients with high CEA, FOLFIRI/Cet compared to FOLFIRI/Bev showed a greater OS benefit (HR = 0.56; P < 0.001) than in patients with low CEA (HR = 0.78; P = 0.30). Furthermore, FOLFIRI/Cet exhibited significantly superior objective response rate in patients with high CEA (odds ratio = 2.21; P = 0.006) in contrast to patients with low CEA (odds ratio = 0.90; P = 0.85). CONCLUSION: In patients with RAS-WT mCRC receiving first-line chemotherapy with FOLFIRI/Cet versus FOLFIRI/Bev, elevated CEA was associated with inferior survival in the bevacizumab arm, while this was not the case when cetuximab was applied. Comparison of OS and objective response rate according to treatment arms indicated that cetuximab was greatly superior to bevacizumab in patients with elevated CEA, while this effect was markedly lower and lost statistical significance in patients with low CEA.
Authors: Tomasz Sawicki; Monika Ruszkowska; Anna Danielewicz; Ewa Niedźwiedzka; Tomasz Arłukowicz; Katarzyna E Przybyłowicz Journal: Cancers (Basel) Date: 2021-04-22 Impact factor: 6.639