508PD - 2nd-line therapies after 1st-line therapy with FOLFIRI in combination with cetuximab or bevacizumab in patients with KRAS wild-type metastatic colo...

Date 27 September 2014
Event ESMO 2014
Session Gastrointestinal tumours, colorectal
Topics Anti-Cancer Agents & Biologic Therapy
Colon Cancer
Rectal Cancer
Presenter Dominik Modest
Citation Annals of Oncology (2014) 25 (suppl_4): iv167-iv209. 10.1093/annonc/mdu333
Authors D.P. Modest1, S. Stintzing1, L. Fischer von Weikersthal2, T. Decker3, A. Kiani4, U. Vehling-Kaiser5, S. Al-Batran6, T. Heintges7, C. Lerchenmüller8, C. Kahl9, G. Seipelt10, F. Kullmann11, M. Stauch12, W. Scheithauer13, S. Held14, C. Giessen1, A. Jung15, T. Kirchner15, V. Heinemann1
  • 1Department Of Medical Oncology And Comprehensive Cancer Center, University of Munich, 81377 - Munich/DE
  • 2Oncological Practice, Gesundheitszentrum St. Marien, Amberg/DE
  • 3Private Practice, Onkologische Schwerpunktpraxis, DE-88214 - Ravensburg/DE
  • 4Department Of Medicine Iv, Klinikum Bayreuth, Bayreuth/DE
  • 5Hematoonkology, Schwerpunktpraxis für Hämatologie, Onkologie und Palliativmedizin Praxis Dr. Vehling - Kaiser, 84028 - Landshut/DE
  • 6Medizinische Klinik Ii Für Hämatologie Und Onkologie, Institut für klinische Forschung (IKF) am Krankenhaus Nordwest - UCT, Universitäres Centrum für Tumorerkrankungen Frankfurt, 60488 - Frankfurt am Main/DE
  • 7Medical Department Ii, Lukaskrankenhaus Neuss, 41464 - Neuss/DE
  • 8Onkologie, Onkologisches Zentrum Münster, Münster/DE
  • 9Hematology/ Oncology, Klinikum Magdeburg, DE-39130 - Magdeburg/DE
  • 10Medical Oncology, Onkologische Schwerpunktpraxis Bad Soden, Bad Soden/DE
  • 11Department Of Medicine I, Kliniken Nordoberpfalz - Weiden, 92637 - Weiden/DE
  • 12Hematology And Oncology, University of Munich, 81377 - Munich/DE
  • 13Oncology, Medical University of Vienna, AT-1090 - Wien/AT
  • 14Statistics, ClinAssess GmbH, 51379 - LEverkusen/DE
  • 15Institute Of Pathology, University of Munich, München/DE



To investigated choice and duration of 2nd-line therapies according to 1st-line efficacy as well as overall survival (OS) according to 2nd-line therapy in FIRE-3: FOLFIRI plus either cetuximab (arm a) or bevacizumab (arm b) as 1st-line treatment of KRAS exon 2 wild-type mCRC.


The study-protocol recommended 2nd-line therapy with FOLFOX plus bevacizumab in arm A and irinotecan plus cetuximab in arm B, but physician were free to choose any regimen. 2nd-line treatment was defined as any new anticancer drug for mCRC following 1st-line therapy. Duration of 2nd-line therapy was calculated as time from first to last application of 2nd-line treatment.


260/297 patients in arm A and 250/295 patients in arm B were alive after 1st-line therapy. Of those, 78.5% of patients arm A and 76.4% in arm B received 2nd-line therapy so far. 1st-line PFS according to 2nd-line antibody use was 9.2 (anti-VEGF), comparing to 9.7 (anti-EGFR) and 11.3 months (no mAB); p = 0.001. Correspondingly, OS was 25.2 (anti-VEGF) vs. 23.7 (anti-EGFR) vs. 30.8 months (no mAB), p = 0.02. 1st-line PFS according to 2nd-line oxaliplatin (Ox) use was associated with 9.9 (Ox), comparing to 9.9 months (no Ox); p = 0.56. OS according to Ox-use was 27.1 (ox) vs. 29.1 months (no Ox); p = 0.10. 2nd-line therapy was administered for a median of 17.2 weeks in arm A and 14.0 weeks in arm b (p = 0.08). 2nd-line regimens with antibody-crossover were administered for a median of 23.9 weeks in arm A and 16.1 weeks arm B (p = 0.06). Updated results might be presented at the meeting.


This post-hoc analysis indicates that 2nd-line application of mAbs was favoured in patients with shorter 1st-line PFS. Correspondingly, 2nd-line treatment without antibodies compared to antibody-based regimens was associated with longer OS. A trend towards longer 2nd-line therapy was observed in favour of patients receiving cetuximab as 1st-line therapy.


S. Stintzing: Advisory boards: Roche/Genentech, BMS, Merck Honoraria: Roche/Genentech, Amgen, Merck, Sanofi Travel support: MerckSerono, Roche;L. Fischer von Weikersthal: Travel support: Roche;F. Kullmann: Honoraria: Roche;W. Scheithauer: Advisory boards and honoraria: MerckSerono, Roche; C. Giessen: Travel support: Roche;A. Jung: Advisory boards, and honoraria: MerckSerono;T. Kirchner: Advisory boards: Novartis, Amgen, Pfizer, Roche Honoraria: MerckSerono, Amgen, Roche, AstraZeneca research funding: MerckSerono, Amgen:V. Heinemann: Research grant: MerckSerono, Roche, Amgen Honoraria and advisory boards: MerckSerono, Roche, Amgen Travel support: MerckSerono. All other authors have declared no conflicts of interest.