498O - Maintenance strategy with fluoropyrimidines (FP) plus bevacizumab (Bev), Bev alone or no treatment, following a 24-week first-line induction with F...

Date 27 September 2014
Event ESMO 2014
Session Gastrointestinal tumours, colorectal
Topics Anti-Cancer Agents & Biologic Therapy
Colon Cancer
Rectal Cancer
Presenter Susanna Hegewisch-Becker
Citation Annals of Oncology (2014) 25 (suppl_4): iv167-iv209. 10.1093/annonc/mdu333
Authors S. Hegewisch-Becker1, U. Graeven2, C. Lerchenmüller3, B. Killing4, R. Depenbusch5, C. Steffens6, S. Al-Batran7, T. Lange8, G. Dietrich9, J. Stoehlmacher10, A. Tannapfel11, A. Reinacher-Schick12, J. Quidde13, A. Hinke14, D. Arnold15, H. Schmoll16
  • 1Private Practice, HOPE, 20249 - Hamburg/DE
  • 2Chefarzt Privatdozent, Kliniken Maria Hilf GmbHKlinik f, DE-41063 - Mönchengladbach/DE
  • 3Private Practice, Hämatologisch-onkologische Gemeinschaftspraxis, 48149 - Münster/DE
  • 4Hämatologie-onkologie, Lahn-Dill-Kliniken, 35578 - Wetzlar/DE
  • 5Onkodoc Gmbh, Private Practice, 33332 - Gütersloh/DE
  • 6Private Practice, Schwerpunktpraxis Hämatologie-Onkologie, 21680 - Stade/DE
  • 7Institut Für Klinisch-onkologische Forschung, Krankenhaus Nordwest, 60488 - Frankfurt/DE
  • 8Hämatologie Und Internistische Onkologie, Asklepios Klinikum, 06667 - Weissenfels/DE
  • 9Klinik Für Hämato-onkologie, Krankenhaus Bietigheim, 74321 - Bietigheim-Bissingen/DE
  • 10Tumorgenetik Bonn, Kooperation für Tumordiagnostik, 5311 - Bonn/DE
  • 11Institut Für Pathologie, Ruhr-Universität Bochum, 44789 - Bochum/DE
  • 12Abteilung Für Hämatologie Und Onkologie, St. Josef-Hospital, Universitätsklinikum der Ruhr-Universität, 44791 - Bochum/DE
  • 13Hubertus-wald Tumorzentrum, Universitätsklinikum Eppendorf, 20246 - Hamburg/DE
  • 14Biostatistics, WiSPWissenschaftlicher Service Pharma GmbH, 40764 - Langenfeld/DE
  • 15Internistische Onkologie, Klinik für Tumorbiologie, 79106 - Freiburg/DE
  • 16Innere Medizin Iv, Universitätsklinikum Halle (Saale), 06120 - Halle/DE

Abstract

Aim

AIO KRK 0207 investigates which maintenance strategy, no treatment or Bev alone, is non-inferior to FP plus Bev, following a 24-week induction with FP/Ox/Bev.

Methods

Following registration pts received induction treatment with FP/Ox/Bev. Pts without progression after 24 weeks were randomized into arms: A) standard maintenance with FP plus Bev; B) Bev alone; or C) observation. At first progression, re-induction of the initial treatment was planned. Primary endpoint was the "time to failure of strategy" (TFS), including maintenance plus re-induction after first progression. Secundary endpoints included time to first progression (PFS1) and overall survival (OS).

Results

837 pts were enrolled, 473 randomized. Primary tumor was resected in 74% of pts, 56% had involvement of >1 site. Median PFS1 in arms A, B, C were 6.2 vs 4.8 vs 3.6 mos., respectively (logrank p value: <0.0001). After PFS1, only 21%, 43% and 45% were re-induced. For TFS, arm C is slightly inferior compared to arm A (median: 6.8 vs. 6.1 mos., HR 1.22, 95% CI 0.96-1.57, p = 0.11), but without difference between arms A and B (HR 0.98, 95% CI 0.76-1.26, p = 0.85). With currently limited follow up and 203 documented events, OS does not differ between treatment arms (median: 23.8, 26.2 and 23.1 mos., p = 0.70). 60% of pts had CR/PR after induction, 40% SD. TFS of pts with CR/PR is superior to pts with SD (median 7.5 vs. 4.6 mos., p < 0.0001). In pts with SD, arm A seems to be superior to B (and C), whereas there is no difference between all arms in pts with CR/PR. "All RAS" status was centrally assessed in 337 (71%) of pts; 42% were wild-type (wt) and 58% mutant (mut). TFS of pts with RAS wt is marginally superior to pts with RAS mut (median 8.5 vs. 7.1 mos., p = 0.047). In pts with RAS wt, A and B are superior to C, whereas there is no difference between all arms in pts with RAS mut. Global quality of life did not differ between arms.

Conclusions

With respect to the primary endpoint TFS, our findings suggest that maintenance with Bev mono is non-inferior to FP/Bev. Updated results including OS, multivariate analyses and sequential treatment data will be presented.

Disclosure

S. Hegewisch-Becker: Advisory role: Merck, Roche, Lilly; C. Steffens: Advisory role: Roche; A. Reinacher-Schick: Advisory role: Amgen,Roche,Sanofi, Merck Honoraria: Amgen, Roche, Sanofi, Merck, Pfizer Research funding: Roche Sanofi; D. Arnold: Advisory role: Merck, Roche; H. Schmoll: Advisory role: Roche. All other authors have declared no conflicts of interest.