Updated results of the FIRIS study: A phase II/III trial of 5-FU/l-leucovorin/irinotecan (FOLFIRI) versus irinotecan/S-1 (IRIS) as second-line chemotherapy for metastatic colorectal cancer (mCRC).

Abstract

Listen

Translate article

3562 Background: The FIRIS study (Muro K et al. Lancet Oncol 2010;11:853–860) previously demonstrated the non-inferiority of IRIS to FOLFIRI, with progression-free survival (PFS) as the primary endpoint. We now report the final results of this study. Methods: The FIRIS study is a randomized, prospective, open-label, phase II/III study. Irinotecan (IRI)-naïve mCRC patients with one prior chemotherapy regimen, ECOG PS 0–1, and adequate organ function were randomized to receive either FOLFIRI (200 mg/m2 of l-leucovorin given simultaneously with 150 mg/m2 of IRI, followed by a 400 mg/m2 bolus of 5-FU on day 1, and then 2,400 mg/m2 of 5-FU over 46 h, every 2 weeks) or IRIS (125 mg/m2 of IRI on days 1 and 15, and 40–60 mg/body of S-1 twice daily for 2 weeks, followed by a 2-week rest). The primary endpoint was PFS. Secondary endpoints were overall survival (OS), response rate (RR), safety, and treatment cost. Patient information was updated in July 2010. Results: At this final analysis, median follow-up was 3.11 years. Median PFS was 5.1 months (95% CI: 4.2–6.0) in the FOLFIRI group and 5.8 months (95% CI: 4.5–6.0) in the IRIS group (adjusted HR=1.058, 95% CI: 0.869–1.289, p=0.022 for non-inferiority), which is consistent with earlier results (HR=1.077, 95% CI: 0.869-1.319, p=0.039). Median OS was 17.5 months (95% CI: 14.9–19.4) in the FOLFIRI group and 18.0 months (95% CI: 15.0-21.0) in the IRIS group (adjusted HR=0.901, 95%CI: 0.728-1.115 p=0.0003 for non-inferiority). In patients with prior oxaliplatin treatment, median OS was 15.3 and 13.3 months in the IRIS and FOLFIRI groups, respectively (adjusted HR=0.773, 95% CI: 0.593–1.007), whereas in patients without prior oxaliplatin treatment it was 23.6 and 26.9 months, respectively (adjusted HR=1.188, 95% CI: 0.833–1.694). Conclusions: The non-inferiority of IRIS to FOLFIRI, with PFS and OS as endpoints, is reconfirmed. Thus, IRIS can be an additional second line option for mCRC treatment.