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AIO 0207

Randomized Three Arm Phase III Trial on Induction Treatment with a Fluoropyrimidine-, Oxaliplatin- and Bevacizumab-based Chemotherapy for 24 Weeks Followed by Maintenance Treatment With a Fluoropyrimidine and Bevacizumab vs. Bevacizumab Alone vs. no Maintenance Treatment and Reinduction in Case of Progression for First-line Treatment of Patients With Metastatic Colorectal Cancer

Phase 3N = 472NCT00973609

Population
Previously untreated metastatic colorectal cancer without progression after 24 weeks of induction with a fluoropyrimidine, oxaliplatin and bevacizumab
Design
Open-label, non-inferiority randomised phase 3 trial in Germany (55 hospitals and 51 private practices): after 24 weeks of induction (fluorouracil plus leucovorin plus oxaliplatin, or capecitabine plus oxaliplatin, both with bevacizumab), patients without progression were randomly assigned (1:1:1) to standard maintenance fluoropyrimidine plus bevacizumab, bevacizumab alone, or no treatment. Re-induction at first progression was a planned part of the protocol. The primary endpoint was time to failure of strategy (non-inferiority boundary: upper limit of the one-sided 98.8% CI 1.43); analyses were by intention to treat. 837 patients were enrolled and 472 randomised (158, 156 and 158).
Primary endpoint
Time to failure of strategy
Arms
  • Fluoropyrimidine plus bevacizumab (control, n = 158): Standard maintenance fluoropyrimidine plus bevacizumab
  • Bevacizumab alone (experimental, n = 156): Maintenance bevacizumab monotherapy
  • No treatment (experimental, n = 158): No maintenance treatment
People
Hegewisch-Becker S
Time to failure of strategyHR 1.08 (95% CI 0.85–1.37)Δ median Time to failure of strategy−0.8 monthsTime to failure of strategyHR 1.26 (95% CI 0.99–1.60)Δ median Time to failure of strategy−0.5 months
Show the numbers
Results reported for AIO 0207
EndpointAnalysisBevacizumab alone / No treatmentFluoropyrimidine plus bevacizumabEffect
Time to failure of strategyprimarymedian follow-up 17 monthsHegewisch-Becker 2015median 6.1 months (5.3–7.4)median 6.9 months (6.1–8.5)HR 1.08 (95% CI 0.85–1.37)P=0.53Bevacizumab alone was non-inferior to fluoropyrimidine plus bevacizumab: upper limit of the one-sided 99.8% CI 1.42 (boundary 1.43 stated as the one-sided 98.8% CI).
Time to failure of strategyprimarymedian follow-up 17 monthsHegewisch-Becker 2015median 6.4 months (4.8–7.6)median 6.9 months (6.1–8.5)HR 1.26 (95% CI 0.99–1.60)P=0.056No treatment was not shown to be non-inferior: upper limit of the one-sided 99.8% CI 1.65.
Results reported for AIO 0207
EndpointAnalysisBevacizumab alone / No treatmentFluoropyrimidine plus bevacizumabEffect
Time to failure of strategyprimarymedian follow-up 17 monthsHegewisch-Becker 2015median 6.1 months (5.3–7.4)median 6.9 months (6.1–8.5)HR 1.08 (95% CI 0.85–1.37)P=0.53Bevacizumab alone was non-inferior to fluoropyrimidine plus bevacizumab: upper limit of the one-sided 99.8% CI 1.42 (boundary 1.43 stated as the one-sided 98.8% CI).
Time to failure of strategyprimarymedian follow-up 17 monthsHegewisch-Becker 2015median 6.4 months (4.8–7.6)median 6.9 months (6.1–8.5)HR 1.26 (95% CI 0.99–1.60)P=0.056No treatment was not shown to be non-inferior: upper limit of the one-sided 99.8% CI 1.65.
Hazard ratio (95% CI) by endpoint. Values below 1 favour the experimental arm.
Time to failure of strategyTime to failure of strategy0.512◀ experimentalcontrol ▶
Data table
EndpointHR95% CI
Time to failure of strategy1.080.85–1.37
Time to failure of strategy1.260.99–1.6
Illustrative — modelled from reported values, not trial data. Time to failure of strategy, primary.
0%25%50%75%100%051015Months (modelled)
  • Bevacizumab alone (experimental)
  • Fluoropyrimidine plus bevacizumab (control)

Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.

Data table (modelled values)
MonthsBevacizumab aloneFluoropyrimidine plus bevacizumab
0100.0%100.0%
463.5%66.9%
936.0%40.5%
1322.8%27.1%
1714.5%18.1%
Illustrative — modelled from reported values, not trial data. Time to failure of strategy, primary.
0%25%50%75%100%051015Months (modelled)
  • No treatment (experimental)
  • Fluoropyrimidine plus bevacizumab (control)

Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.

Data table (modelled values)
MonthsNo treatmentFluoropyrimidine plus bevacizumab
0100.0%100.0%
464.8%66.9%
937.7%40.5%
1324.5%27.1%
1715.9%18.1%
Primary publication: Hegewisch-Becker S, Graeven U, Lerchenmüller CA, Killing B, Depenbusch R, Steffens CC, et al. Maintenance strategies after first-line oxaliplatin plus fluoropyrimidine plus bevacizumab for patients with metastatic colorectal cancer (AIO 0207): a randomised, non-inferiority, open-label, phase 3 trial. Lancet Oncol. 2015;16(13):1355-69. PubMedDOI

Appears in

Sources

  1. Hegewisch-Becker S, Graeven U, Lerchenmüller CA, Killing B, Depenbusch R, Steffens CC, et al. Maintenance strategies after first-line oxaliplatin plus fluoropyrimidine plus bevacizumab for patients with metastatic colorectal cancer (AIO 0207): a randomised, non-inferiority, open-label, phase 3 trial. Lancet Oncol. 2015;16(13):1355-69.

    PubMedDOI