Answer to Quiz, Discussion, and Conclusion

[摘要] Purpose 5-Fluorouracil/leucovorin, oxaliplatin, irinotecan(FOLFOXIRI) plus bevacizumab is more effective thandoublets plus bevacizumab as first-line therapy formetastatic colorectal cancer, but is not widely usedbecause of concerns about toxicity and lack of predictivebiomarkers. This study was designed to explore the roleof circulating tumour cell (CTC) count as a biomarker toselect patients for therapy with FOLFOXIRI-bevacizumab.Patients and methods VISNÚ-1 was a multicentre,open-label, randomised, phase III study in patients withpreviously untreated, unresectable, metastatic colorectalcarcinoma and ≥3 CTC/7.5mL blood. Patients receivedbevacizumab 5 mg/kg plus FOLFOXIRI (irinotecan 165mg/m2, oxaliplatin 85 mg/m2, leucovorin 400 mg/m2 and5-fluorouracil 3200 mg/m2) or FOLFOX (oxaliplatin 85mg/m2, leucovorin 400 mg/m2, 5-fluorouracil 400 mg/m2then 2400 mg/m2) by intravenous administration every2 weeks. The primary outcome was progression-freesurvival (PFS).Results The intention-to-treat population comprised349 patients (FOLFOXIRI-bevacizumab, n=172; FOLFOXbevacizumab, n=177). Median PFS was 12.4 months(95%CI 11.2 to 14.0) with FOLFOXIRI bevacizumab and 9.3months (95%CI 8.5 to 10.7) with FOLFOX-bevacizumab(stratified HR, 0.64; 95%CI 0.49 to 0.82; p=0.0006).Grade≥3 adverse events were more common withFOLFOXIRI-bevacizumab 85.3% vs 75.1% with FOLFOXbevacizumab (p=0.0178). Treatment-related deathsoccurred in 8 (4.7%) and 6 (3.4%) patients, respectively.Conclusions First-line FOLFOXIRI-bevacizumabsignificantly improved PFS compared with FOLFOXbevacizumab in patients with metastatic colorectal cancerand ≥3 CTCs at baseline, which indicate a poor prognosis.CTC count may be a useful non-invasive biomarker toassist with the selection of patients for intensive first-linetherapy.

[学科分类] 生理学与病理学