CAIRO6 trial

Background

Randomised, open-label phase 3 trial at 10 Dutch/Belgian tertiary centres. N=358 (351 modified-ITT) with WHO PS 0-1 and resectable colorectal peritoneal-only metastases, no systemic therapy for ≥6 months. Tested whether perioperative systemic therapy added to cytoreductive surgery with HIPEC (CRS-HIPEC) improves survival versus upfront CRS-HIPEC alone.

Results

Interventions and follow up: Arm A: Perioperative systemic therapy (neoadjuvant + adjuvant CAPOX or FOLFOX/FOLFIRI, ± bevacizumab neoadjuvantly) plus CRS-HIPEC (n=180)
Arm B: Upfront CRS-HIPEC alone (n=178)
Primary endpoint: Overall survival (modified ITT)
mFollow up: 41 months
Results: OS: 44 mo vs 39 mo, HR 0.85 (95% CI 0.62–1.15), P=.28 (not significant)

Adverse events

Major 90-day postoperative morbidity (Clavien-Dindo 3-5): 36% vs 26%
Major systemic therapy toxicity (CTCAE 3-5): 57% of those who started it
90-day postoperative mortality: ~1% in both arms

Conclusions

Perioperative systemic therapy did not improve overall survival in resectable colorectal peritoneal-only metastases and added morbidity. It cannot be recommended for all such patients.

Key Limitations

Open-label design; investigators chose among heterogeneous chemotherapy regimens and HIPEC agents (oxaliplatin- or mitomycin-based), limiting interpretation. The sample size is modest for an OS endpoint, and subgroups that might benefit (e.g., high peritoneal cancer index or adverse biology) were not prospectively defined.

Clinical Context

CRS-HIPEC is the standard for selected resectable colorectal peritoneal metastases, though PRODIGE-7 showed oxaliplatin-based HIPEC adds nothing to cytoreductive surgery. CAIRO6 now argues against routine perioperative systemic therapy in this setting, contrasting with the usual perioperative-chemotherapy convention. No regulatory implication.

References