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 Anticancer Agents
Colon and Rectal Cancer
Biological Therapy
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.