QUASAR

Background

Phase III, open-label RCT. 3239 patients with curatively resected colorectal cancer (colon 71%, rectal 29%), predominantly stage II (71%), comparing adjuvant fluorouracil-based chemotherapy to observation. Tested whether adjuvant 5-FU provides meaningful benefit in the stage II (lower-risk) colon cancer population where benefit is widely debated.

Interventions and follow up

Arm A: Fluorouracil 370mg/m² + folinic acid 175mg/m² IV q4wk × 24 wks (6 cycles) — capecitabine 1250mg/m² BID D1-14 q3wk was used in ~650 patients per a parallel randomization
Arm B: Observation (no adjuvant chemotherapy)
Primary endpoint: Recurrence and mortality
mFollow up: 5.5 yr

Results

Recurrence risk ratio (chemotherapy vs observation): 0.78, 95% CI 0.67–0.91, P=.001
Mortality risk ratio: 0.82, 95% CI 0.70–0.95, P=.008
Absolute OS benefit (5-yr): ~3.6% (from 80.3% to 83.9%)
Capecitabine vs 5-FU (secondary): Similar relapse rate (RR 1.06, 95% CI 0.88–1.26) — non-inferior

Adverse events

GI/mucosal: Grade ≥3 AEs 18.6% (5-FU) vs 11.1% (observation); diarrhea grade ≥3 4.5%; mucositis grade ≥3 1.7%; hand-foot syndrome (capecitabine) 3.1%
Hematologic: Neutropenia grade ≥3 6.2%; one treatment-related death (0.1%)

Conclusions

Adjuvant fluorouracil-based chemotherapy significantly reduced recurrence and improved survival in patients with resected stage II (predominantly) and stage III colorectal cancer, with an absolute 5-year OS benefit of approximately 3.6%. QUASAR provided definitive evidence supporting adjuvant chemotherapy even in stage II CRC, where the absolute benefit is modest but statistically significant.

Key Limitations

Key Limitations: The 3.6% absolute OS benefit in primarily stage II CRC is modest — for every 100 treated, approximately 3–4 avoid death at 5 years — raising questions about whether the benefit justifies treatment for all stage II patients. Stage II was not pre-stratified by prognostic features (T4, LVI, obstruction, poor differentiation), preventing identification of which stage II patients benefit most. The pre-microsatellite instability era trial did not account for MMR/MSI status, and stage II MSI-H CRC is now known to derive no benefit from 5-FU-based chemotherapy. Capecitabine non-inferiority was secondary and underpowered.

Clinical Context

QUASAR remains the key evidence base for adjuvant chemotherapy in stage II colon cancer. Current guidelines stratify stage II into low-risk (observation or clinical trial) vs high-risk (T4, LVI, obstruction, perforation, inadequate lymph node sampling, poor differentiation) where adjuvant therapy is considered. Crucially, MSI-H/dMMR stage II colon cancer is now recognized as a subgroup that does NOT benefit from 5-FU-based adjuvant therapy (and may be harmed), making MSI/MMR testing essential in stage II decision-making.

References

References: Gray R et al, Lancet 2007