SCOT

Background

Phase III, open-label RCT. 6088 patients (the largest single contributing trial to the IDEA collaboration) with stage III (and high-risk stage II) colon or rectal cancer after curative resection. UK and Scandinavian multicenter trial comparing 3 vs 6 months of adjuvant oxaliplatin-based chemotherapy. Investigator chose either CAPOX or FOLFOX per patient suitability.

Interventions and follow up

Arm A: 3 months of CAPOX or FOLFOX (investigator choice)
Arm B: 6 months of CAPOX or FOLFOX (investigator choice)
Primary endpoint: Disease-free survival (DFS) non-inferiority (HR ≤1.12)
mFollow up: 74.1 mo

Results

DFS (overall): HR 1.006, 95% CI 0.938–1.079 — non-inferior (both margin and CI below 1.12)
OS: HR 0.97 — similar between arms
DFS (CAPOX subgroup): HR 0.97 — clearly non-inferior
DFS (FOLFOX subgroup): HR 1.04 — non-inferior but narrower margin
Neuropathy grade ≥2: 28% vs 47% (3 vs 6 months)

Adverse events

Neurologic: Grade ≥3 peripheral neuropathy 5% vs 21% (3 vs 6 mo) — dominant safety difference
GI/hematologic/overall: Diarrhea grade ≥3 similar; myelosuppression grade ≥3 9% vs 13%; serious AEs 36% vs 44%; quality of life improved in 3-month arm

Conclusions

Three months of adjuvant oxaliplatin-based chemotherapy was non-inferior to 6 months for DFS and OS in stage III CRC, with substantially less peripheral neuropathy. SCOT provided the largest single-trial evidence base for the IDEA collaboration, confirming that shorter adjuvant therapy duration is appropriate for most stage III colon cancer patients.

Key Limitations

Key Limitations: Regimen (CAPOX vs FOLFOX) was not randomized — investigator or patient preference determined the regimen, potentially introducing selection bias. Overall non-inferiority was demonstrated but the regimen-specific subgroups have less power individually. The trial enrolled some high-risk stage II patients (non-standard in IDEA analysis), slightly broadening the enrolled population. Rectal cancer patients were included (~10%) — though the major findings were in colon cancer populations.

Clinical Context

SCOT is the largest single IDEA-contributing trial and provided strong evidence for 3-month adjuvant oxaliplatin-based chemotherapy. Together with the IDEA pooled analysis and other contributing trials, SCOT has changed standard practice globally: 3-month CAPOX is now preferred for most stage III colon cancer. The neuropathy reduction with 3-month treatment translates to meaningful quality-of-life preservation for patients.

References

References: Iveson TJ et al, Lancet Oncol 2018