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June 06, 2011
Taiho Pharmaceutical Co., Ltd.

Presentation to the American Society of Clinical Oncology of results of final analysis of a clinical study in patients with unresectable colorectal cancer (FIRIS study)

It is reported here that, on June 4 (US time), Taiho Pharmaceutical Co., Ltd., and Daiichi Sankyo Co., Ltd., made a presentation (Abstract no. 3562) to the 47th meeting of the American Society of Clinical Oncology (ASCO) about the results of the final analysis of the FOLFIRI + ISIS (FIRIS) study.

The FIRIS study was a Phase-III clinical study in unresectable colorectal cancer patients, involving comparing, for use as the second-line therapy, FOLFIRI, which is one of the standard treatment methods, with TS-1 + irinotecan combination therapy (IRIS). In the final analysis, the overall survival time with IRIS was shown to be not inferior to that with FOLFIRI.

The results for progression-free survival, which was the primary endpoint in the FIRIS study, were presented in 2009 at a meeting of the European Society for Medical Oncology (Abstract no. 6012), and were published in 2010 (Lancet Oncology, 11 [9]: 853-860, 2010), with a 2009 impact factor of 14.470.

RESULTS OF FINAL ANALYSIS

The median overall survival times were 17.4 months in the FOLFIRI group, and 17.8 months in the IRIS group, showing that IRIS was not inferior to FOLFIRI in this respect (adjusted hazard ratio: 0.900; 95% confidence interval: 0.728 to 1.112; p = 0.0003 for non-inferiority).

The median duration of the monitoring period was 39.2 months The median progression-free survival time was 5.1 months in the FOLFIRI group, and 5.8 months in the IRIS group, again showing that IRIS was not inferior to FOLFIRI (adjusted hazard ratio: 1.058; 95% confidence interval: 0.869 to 1.289; p = 0.022 for non-inferiority).

In addition, IRIS and FOLFIRI were compared in the sub-population previously administered treatment including oxaliplatin (L-OHP), and the overall survival time was found to be longer with IRIS than with FOLFIRI, at 15.3 and 12.7 months, respectively (adjusted hazard ratio: 0.755; 95% confidence interval: 0.580 to 0.983; p < 0.0001 for non-inferiority; p = 0.0358 for superiority).

EndpointTreatment groupResults (months)Hazard ratio (95% confidence interval)p value
Overall survival time FOLFIRI 17.4 0.900 (0.728 to 1.112) p=0.0003 (Non-inferiority)
IRIS 17.8
Progression-free survival time FOLFIRI 5.1 1.058 (0.869 to 1.289) p=0.022 (Non-inferiority)
IRIS 5.8
Overall survival time in patients previously administered L-OHP FOLFIRI 12.7 0.755 (0.580 to 0.983) p<0.0001 (Non-inferiority) p=0.0358 (superiority)
IRIS 15.3

Hideo Baba (Chair of the Department of Gastroenterological Surgery, Kumamoto University), who made a presentation at the 2011 ASCO meeting, made the following comment about the above results:

As second-line treatment for unresectable colorectal cancer, it is possible to replace FOLFIRI with IRIS. Continuous intravenous infusion using a pump could be replaced with TS-1, which is an orally administered anti-cancer agent, which would be of major benefit to the patients. It is particularly significant that, patients previously administered L-OHP had longer overall survival times with IRIS than with FOLFIRI.

IRIS treatment

CPT-11 (irinotecan) was administered at 125 mg/m2 on days 1 and 15, and TS-1 was administered for 2 weeks at a twice daily dose 40 to 60 mg, dependent upon the body surface area. This regimen was repeated at 4-week intervals.

FOLFIRI treatment

After administration of 200 and 150 mg/m2 of l-LV (leucovorin) and CPT-11, respectively, 400 mg/m2 5-FU was administered by rapid intravenous infusion on day 1, followed by 2,400 mg/m2 5-FU by continuous intravenous infusion over 46 hours. This regimen was repeated at 2-week intervals.

FIRIS study

Study name: The FIRIS study was a Phase-II/III clinical study in unresectable colorectal cancer patients, in which CPT-11 + 5-FU + LV (FOLFIRI) and CPT-11 + TS-1 (IRIS) were compared as second-line treatments.

Background: FOLFOX and FOLFIRI are in wide use as first- and second-line treatments for unresectable colorectal cancer. However, 5-FU-based treatment by intravenous administration is not straightforward, because continuous infusion and implanted infusion ports are needed. Therefore, we designed a randomized comparative study to demonstrate the non-inferiority of IRIS in comparison with FOLFIRI, as a second-line treatment for unresectable colorectal cancer patients.

Methodse: The study was carried out at 40 Japanese clinical institutions, between January 30, 2006, and January 29, 2008. Unresectable colorectal cancer patients who required second-line treatment were randomly allocated to the FOLFIRI and IRIS groups, with 213 patients each, all of which gave informed consent to participate. With the FOLFIRI group, 200 mg/m2 1-LV and 150 mg/m2 CPT-11 were administered, followed by rapid intravenous infusion of 400 mg/m2 5-FU on day 1, and then continuous intravenous infusion of 2,400 mg/m2 5-FU over 46 hours, with this regimen being repeated at 2-week intervals. With the IRIS group, 125 mg/m2 CPT-11 was administered on days 1 and 15, and TS-1 was administered in twice-daily doses of 40 to 60 mg, dependent upon the body surface area, for 2 weeks, with this regimen being repeated at 4-week intervals. The primary endpoint was progression-free survival time, for which the acceptable limit for non-inferiority was taken to be 1.333.

Statistical analysis was carried out with all allocated patients. This clinical study has been recorded in the ClinicalTrial.gov website.

Information in this news release was current as of the original release date.

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