First Report of a Phase Ii Trial of Irinotecan Plus S-1 (Iris) with Cetuximab (Iris/Cet) in Pre-Treated Patients with Kras Wild Type of Metastatic Colorectal Cancer (Mcrc): Hgcsg0902

Aim: IRIS is one of the standard regimens as second line treatment in mCRC since IRIS demonstrated the non-inferiority to FOLFIRI (FIRIS study) in Japan. From the results of 20050181 trial, FOLFIRI/panitumumab significantly improved PFS and is well-tolerated as second-line treatment in patients with KRAS wild type of mCRC. Thus we conduct the study of IRIS/Cet (HGCSG0902). Methods: HGSCG0902 is a multicenter phase ll study. Eligibility includes histologically confirmed colorectal cancer, previously received oxaliplatin-contained chemotherapy, PS: 0-1, EGFR positive and KRAS Exon2 wild type. Patients (pts) received S-1 80-120 mg/day p.o. on days 1-14 and irinotecan 100mg/m2 on days 1 and 15 repeated every 28 days. Cetuximab was administrated 400mg/m2 loading dose and continued 250mg/m2 every week or 500mg/m2 bi-weekly. The primary endpoint was response rate and the secondary endpoints were disease control rate, PFS, OS and safety. We estimated that a target sample size of 76 patients. Results: Between Mar 2010 and September 2013, 58 pts were enrolled. One patient was not administered (57 pts were safety analysis set), and 3 pts were ineligible (54 pts were efficacy analysis set). Patients characteristics were as follows: median age 66 years (range 35-79), Male: female 36:21, PS 0:1 38:19. Median number of cycles was 3. The main grade 3-4 AE were diarrhea (35.1%), neutropenia (26.8%), acne like rash (17.5%) and anorexia (15.8%). The median relative dose intensity of IRIS/Cet was 0.818. Response rate was 33.3% (95%CI 20.8-45.9%) and disease control rate was 79.6%. Median progression-free survival was 4.7 months (95%C.I. 3.3-6.1 months). Conclusions: IRIS/Cet appeared to be highly effective with a response rate of 33.3% and progression-free survival of 4.7 months, and had met the primary endpoint. Diarrhea was a major adverse event, but was manageable by dose reduction and supportive care. The final analysis will be presented in 2015 ASCO Annual meeting. Disclosure: S. Yuki: Taiho Pharmaceutical, Chugai Pharmaceutical, Bristol-Myers Squibb, Merck Serono, Takeda Pharmaceutical, Yakult Honsha;M. Nakamura: Takeda Pharmaceutical, Chugai Pharmaceutical, Bayer Yakuhin;Y. Tsuji: Honoraria - Ono Pharmaceutical; Y. Sakata: Taiho Pharmaceutical, Daiichi Sankyo, Yakult Honsha, Otsuka Pharmaceutical, Merck Serono, Bristol-Myers Squibb, Synergy International; Y. Komatsu: Yakult Honsha, Taiho Pharmaceutical, Chugai Pharmaceutical, Merck Serono, Pfizer Japan, Novartis Pharma, Sawai Pharmaceutical, Ono Pharmaceutical, Daiichi Sankyo, Takeda Pharmaceutical, Eli Lilly Japan, Kureha Corporation. All other authors have declared no conflicts of interest.