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Gastrointestinal tumours, colorectal 2

1644 - Sequential first-line therapy of metastatic colorectal cancer (mCRC) starting with fluoropyrimidine (FP) plus bevacizumab (BEV) vs. initial FP plus irinotecan (IRI) and BEV: German AIO KRK0110 (ML22011)- study

Date

11 Sep 2017

Session

Gastrointestinal tumours, colorectal 2

Presenters

Dominik Modest

Citation

Annals of Oncology (2017) 28 (suppl_5): v158-v208. 10.1093/annonc/mdx393

Authors

D.P. Modest1, L. Fischer von Weikersthal2, T. Decker3, U. Vehling-Kaiser4, J. Uhlig5, M. Schenk6, J. Freiberg-Richter7, B. Peuser8, C. Denzlinger9, C. Peveling Genannt Reddemann10, U. Graeven11, G. Schuch12, I. Schwaner13, A. Stahler1, A. Jung14, S. Held15, S. Stintzing1, C. Giessen-Jung1, V. Heinemann1

Author affiliations

  • 1 Medical Dept. Iii, Ludwig Maximilians University - Grosshadern, 81377 - Munich/DE
  • 2 Gesundheitszentrum St. Marien, Gesundheitszentrum St. Marien, Amberg/DE
  • 3 Onkologie-ravensburg, Onkologie-Ravensburg, 88212 - Ravensburg/DE
  • 4 Oncology, Praxis Dr. Vehling-Kaiser, 84028 - Landshut/DE
  • 5 Oncological Practice, Oncological Practice, Naunhof/DE
  • 6 Medical Oncology, Krankenhaus Barmherzige Brüder Regensburg, Regensburg/DE
  • 7 Oncological Practice, Oncological Practice, Dresden/DE
  • 8 Onkologische Praxis Am Diakonissenhaus, Onkologische Praxis am Diakonissenhaus, Leipzig/DE
  • 9 Medical Oncology, Marienhospital Stuttgart, 70199 - Stuttgart/DE
  • 10 Medical Oncology, MVZ RNR Leverkusen am Gesundheitspark, Leverkusen/DE
  • 11 Medical Oncology, Kliniken Maria Hilf GmbH Klinik für Haematolgie/Onkologie, 41063 - Mönchengladbach/DE
  • 12 Hämatologisch-onkologische Praxis Altona (hopa), Hämatologisch-Onkologische Praxis Altona (HOPA), Hamburg/DE
  • 13 Onkologische Schwerpunktpraxis Kurfürstendamm, Onkologische Schwerpunktpraxis Kurfürstendamm, Berlin/DE
  • 14 Pathologisches Institut-lmu München, Ludwig-Maximillians-Universität, 80337 - München/DE
  • 15 Clinassess Gmbh, ClinAssess GmbH, Leverkusen/DE
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Abstract 1644

Background

The AIO KRK-0110 study compares a sequential application of FP+ BEV followed by IRI+ FP+ BEV at first progression (arm A) vs. initial FP+ IRI+ BEV (arm B) in patients (pts) with untreated mCRC.

Methods

The primary efficacy-endpoint was time-to-failure of strategy (TFS). The non-inferiority margin was a 90% confidence interval of a hazard ratio (HR) of 0.8 (Power 70%, α = 0.05). Secondary endpoints of the study included response rate, progression-free survival (PFS), overall survival (OS), efficacy in molecular subgroups and quality of life (EORTC QLQ C30).

Results

The full analysis set (FAS) consists of 421 pts (212/209 Arm A/B), median age was 71 years. The primary endpoint (TFS) was not met (HR: 0.86 (0.73-1.02)). Concerning TFS, patients with RAS/BRAF wild-type (WT) mCRC appeared to have significant benefit from initial irinotecan while this was not observed in patients with mutant (MT) RAS or BRAF. A Cox model interaction test for study arm and RAS-status was significant (P = 0.03). PFS and OS were consistent with TFS (see table for details). Objective response rate favored the initial irinotecan-arm (36.8% vs 53.6%, P = 0.005). Quality of life (global health, physical functioning, etc) was not substantially different between both study arms at baseline and end of treatment.

Conclusions

In this trial comprising a more elderly population, non-inferiority for TFS of initial FP+ BEV as compared to FP+ IRI+ BEV was not shown. In detail, sequential therapy was inferior in pts with RAS/BRAF-WT mCRC and cannot be recommended. However, sequential bevacizumab-based therapy could be discussed as an option in elderly pts with RAS MT mCRC. Conclusions on BRAF mutant tumors are limited by sample size.Table:

486O

PopulationPFS-1TFSOS
mo.Hazard ratiomo.Hazard ratiomo.Hazard ratio
(95%CI)P-value(90%CI)P-value(95%CI)P-value
FAS
Arm A (N = 212)8.0 (6.9-9.9)0.70 (0.57-0.85)9.6 (8.6-10.6)0.86 (0.73-1.02)21.9 (20.2-25.0)0.84 (0.66-1.06)
Arm B (N = 209)9.9 (8.7-10.9)P 

Clinical trial identification

NCT01249638

Legal entity responsible for the study

Hospital of the University of Munich (LMU)

Funding

Roche

Disclosure

D. P. Modest: Honoraria/Advisory Boards: Amgen, Merck, Roche, Bayer, Servier, MSD, BMS. Research Grants: Amgen, Merck, Roche. Travel Support: Merck, Amgen, Servier, Bayer, BMS. L. Fischer von Weikersthal: Honoraria: Pfizer. Consulting or Advisory Role: Roche-Peru. Travel, accommodations, expenses: Pfizer, Roche-Peru, AMtene. T. Decker: Travel, accommodations, expenses: Novartis Pharma KK. U. Vehling-Kaiser: Consulting or Advisory Role: Gilead Sciences, MSD, Lilly, Abbvie, Roche Pharma AG, AMtene. U. Graeven: Honoraria: Sanofi, Bayer, Boehringer Ingelheim, Roche-Peru, AMtene. Consulting or Advisory Role: Baxalta, Servier. Travel, accommodations, expenses: Sanofi, Merck Inc. I. Schwaner: Consulting or Advisory Role: Abbvie, Merck Inc., Janssen Corp, Roche-Peru. Travel, accommodations, expenses: Novartis Pharma KK, Roche-Peru. A. Jung: Consulting or Advisory Role: Biocartis, AstraZeneca, Merck Inc., Roche-Peru, AMtene. Speakers\' Bureau: AstraZeneca, Merck Inc., Roche-Peru. Travel, accommodations, expenses: Biocartis, AstraZeneca, Merck Inc., Roche-Peru, AMtene. S. Stintzing: Consulting or Advisory Role: Merck KGA, Roche, Sanofi, Bayer, Amgen, Boehringer Ingelheim, Lilly. Travel, accommodation, expenses: Merck KGA, Roche, Sanofi, Bayer, Amgen, Lilly, Sirtex Medical. Honoraria: Merck KGaA, Roche, Bayer, Amgen, Sanofi, Lilly, Sirtex Medical. VV. Heinemann: Consulting or Advisory Role: Merck, Am., Roche, Sanofi, Boehringer Ingelheim, Celgene, Sirtex Medical, Bax. Travel, accommodation, expenses: Merck, Am., Roche, Sirtex Medical, Bax. Honoraria: Merck, Am., Roche, Sanofi, Celgene, Sirtex Medical, Bax. Research Funding: Merck, Am., Roche, Sanofi, Celgene, Boehringer Ingelheim, Sirtex Medocal, Int.Gen, Taiho, Bayer. All other authors have declared no conflicts of interest

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