Background
Phase III randomized open-label trial. 472 patients with unresectable metastatic colorectal cancer who completed 24 weeks of fluoropyrimidine + oxaliplatin + bevacizumab induction without progression. Three-arm trial comparing maintenance bevacizumab alone, 5-FU/LV + bevacizumab, or observation (with planned reinduction at progression).
Interventions and follow up
Arm A: Bevacizumab 7.5 mg/kg q3wk alone until progression
Arm B: 5-FU 2,000 mg/m² + leucovorin 200 mg/m² q2wk + bevacizumab 5 mg/kg q2wk until progression
Arm C: Observation — no maintenance; reinduction with original oxaliplatin-based regimen + bevacizumab at first progression
Primary endpoint: Time to failure of strategy (TFS); non-inferiority of A vs B; superiority of A or B vs C
Median follow-up: 21 months
Arm B: 5-FU 2,000 mg/m² + leucovorin 200 mg/m² q2wk + bevacizumab 5 mg/kg q2wk until progression
Arm C: Observation — no maintenance; reinduction with original oxaliplatin-based regimen + bevacizumab at first progression
Primary endpoint: Time to failure of strategy (TFS); non-inferiority of A vs B; superiority of A or B vs C
Median follow-up: 21 months
Results
TFS (Arm A vs B): 6.2 vs 6.9 months, HR 1.08 (95% CI 0.85–1.37), non-inferiority met (P=.019)
TFS (Arm B vs C): 6.9 vs 4.6 months, HR 0.63 (95% CI 0.48–0.83), P<.001
mPFS (Arm A vs C): 4.8 vs 3.3 months, HR 0.67, P=.005
mOS: not significantly different (Arm A 23.5, Arm B 25.4, Arm C 23.1 months)
TFS (Arm B vs C): 6.9 vs 4.6 months, HR 0.63 (95% CI 0.48–0.83), P<.001
mPFS (Arm A vs C): 4.8 vs 3.3 months, HR 0.67, P=.005
mOS: not significantly different (Arm A 23.5, Arm B 25.4, Arm C 23.1 months)
Adverse events
Overall grade ≥3: 8% (bevacizumab alone, Arm A) vs 23% (5-FU+bevacizumab, Arm B)
Most common grade ≥3 (Arm B): hand-foot syndrome, mucositis, diarrhea; hypertension grade ≥3 ~5% in both bevacizumab arms
QoL: favored Arm A over Arm B
Most common grade ≥3 (Arm B): hand-foot syndrome, mucositis, diarrhea; hypertension grade ≥3 ~5% in both bevacizumab arms
QoL: favored Arm A over Arm B
Conclusions
Bevacizumab alone maintenance was non-inferior to 5-FU/LV + bevacizumab for TFS, with substantially lower toxicity and better quality of life. Both maintenance arms were superior to observation, establishing bevacizumab monotherapy as a valid, less toxic maintenance option after fluoropyrimidine/oxaliplatin/bevacizumab induction.
Key Limitations
OS was not significantly different across arms, limiting survival impact conclusions. The novel TFS endpoint reflects clinical strategy rather than direct survival gain. Three-arm design required multiple comparisons. Generalizability is primarily to patients completing oxaliplatin-based (not irinotecan-based) induction. Reinduction eligibility varied across centers. The trial predates routine biomarker stratification (RAS/BRAF testing).
Clinical Context
AIO 0207 complemented CAIRO3 in establishing the maintenance paradigm for mCRC. The key finding — bevacizumab alone is non-inferior to fluoropyrimidine + bevacizumab and less toxic — has influenced practice, particularly in patients developing fluoropyrimidine toxicity. ESMO endorses both bevacizumab alone and fluoropyrimidine + bevacizumab as maintenance options after oxaliplatin-based induction; observation alone is no longer a default approach.