O-0027 - A phase III trial of fluoropyrimidines (fp) plus bevacizumab (bev) vs. Bev alone, or no treatment as maintenance strategy, following a standard comb...

Date 28 June 2014
Event World GI 2014
Session Metastatic colorectal cancer
Topics Anti-Cancer Agents & Biologic Therapy
Colon Cancer
Rectal Cancer
Presenter Dirk Arnold
Citation Annals of Oncology (2014) 25 (suppl_2): ii105-ii117. 10.1093/annonc/mdu193
Authors C.C. Steffens1, J. Quidde2, T. Lange3, G. Dietrich4, J. Stoehlmacher5, A. Reinacher-Schick6, T. Graeven7, S. Hegewisch-Becker8, B. Killing9, R. Depenbusch10
  • 1Klinikum Stade, Stade/DE
  • 2University Cancer Canter Hamburg (UCCH), Hamburg/DE
  • 3Alsklepios Kliniken, Weissenfels/DE
  • 4Klinikum Bietigheim, Bietigheim-Bissingen/DE
  • 5Institut fuer Tumorgenetik, Bonn/DE
  • 6Ruhr University, Bochum/DE
  • 7Kliniken Maria Hilf, Moenchengladbach/DE
  • 8Onkologische Praxis Eppendorf, Hamburg/DE
  • 9Lahn-Dill-Kliniken, Wetzlar/DE
  • 10Schwerpunktpraxis Onkologie und Hämatologie, Gütersloh/DE

Abstract

Introduction

The optimal maintenance strategy following combination chemotherapy plus Bev as a standard “induction” therapy is still controversial. The AIO KRK 0207 phase III trial investigates whether no continuation of therapy or continuation with Bev alone are non-inferior to FP plus Bev, following a 24-week treatment interval with FP/Ox/Bev.

Methods

Pts with mCRC and ‘standard’ eligibility criteria were enrolled. After 24 weeks of induction treatment with FP/Ox/Bev, pts without disease progression were randomized into one of the following arms: A) standard maintenance treatment with FP plus Bev; B) Bev alone; or C) no treatment. At first progression, re-induction of the initial treatment was planned. The primary endpoint was ‘time to failure of strategy’ (TFS), comprising maintenance plus re-induction of the initial treatment after first progression. Sample size was calculated (one-sided alpha of 0.0125; power of 80%) to conclude non-inferiority of arms B or C compared with the standard FP plus Bev arm. Secondary endpoints included time to first progression (PFS1) and overall survival (OS).

Results

840 pts were enrolled, 473 randomized. Median follow-up is 27 months. After induction with FP/Ox/Bev, 60% of pts had CR/PR, 40% SD. Median PFS1 in arms A, B, C were 6.2, 4.6 and 3.6 months (p < 0.0001; A vs C: HR 2.11, 95% CI 1.63-2.73; A vs B: HR 1.28, 95% CI 0.99-1.65; B vs C: HR 1.56, 95% CI 1.22-1.99), respectively. TFS favored arm A over arm C (HR 1.31, 95% CI 1.01-1.69, p = 0.038) but without difference between arms A and B (HR 1.04, 95% CI 0.81-1.36, p = 0.74). However, upon first progression only 24% in arm A and 47% in both, arms B and C, received re-induction of FP/Ox/Bev. After 200 documented events, current preliminary OS is 23.4 months from randomization, without significant difference between treatment arms (p = 0.69).

Conclusion

Following 24 weeks of a standard induction with FP/Ox/Bev, a maintenance strategy with one of the both active maintenance regimen (FP plus Bev or Bev alone), show prolonged TFS compared to no treatment. Only a minority of patients received re-induction treatment as planned. With currently limited follow up, the different maintenance strategies had no impact on OS.