Updated analysis of phase II trial of irinotecan/s-1/cetuximab (IRIS/Cet) as second-line treatment in patients with KRAS exon2 wild type metastatic colorectal cancer (mCRC): HGCSG0902—Comparison of administration interval in cetuximab treatment.
771 Background: HGCSG0902 is the multicenter phase II study to investigate the safety and efficacy of irinotecan, S-1 (IRIS) plus cetuximab as second line treatment in patients with KRAS exon2 wild type mCRC. Response rate (RR) was 33.3% (95%CI 20.8-45.9%), therefore primary endpoint was met (Muto O, et al. ESMO 2014). Here we report an exploratory analysis of outcomes based on administration interval of cetuximab (every week [EW] vs bi-weekly [BW]). Methods: Eligibility includes histologically confirmed mCRC, previously received oxaliplatin-contained chemotherapy, PS: 0-1, EGFR positive and KRAS exon2 wild type. Patients received S-1 80-120 mg/day p.o. on days 1-14 and irinotecan 100mg/m2 on day 1 and 15 repeated every 28 days. Cetuximab was administrated 400mg/m2 as loading dose and continued 250mg/m2 every week or 500mg/m2 bi-weekly. The primary endpoint was RR and the secondary endpoints were disease control rate, PFS, OS and safety. To compare with EW and BW, Fisher’s exact test was used in terms of patient characteristics, AE, RR, and Log-rank test was used in terms of PFS and OS. Results: Between Mar 2010 and Sep 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). Based on each physician’s choice, 34 patients of EW and 23 of BW were included in the full safety analysis set. RR was 34.4% in the EW and 31.8% in the BW (p = 1.000). Median PFS was 4.2 months in the EW and 6.1 months in the BW (HR 0.752, p = 0.350). Median OS was 8.9 months in the EW and 10.7 months in the BW (HR 0.902, p = 0.737). The most common non-hematological adverse events of grade 3 or higher were diarrhea (23.5% in the EW vs 52.2% in the BW: p = 0.005) and stomatitis (2.9% in the EW vs 30.4% in the BW group: p = 0.046), these were significantly more common in the BW. Conclusions: IRIS/Cet appeared to be highly effective with RR, PFS and OS in the both treatment schedule. Diarrhea and stomatitis were significantly more common in the BW. Therefore, in case of treatment with IRIS/Cet should be administered in the EW. Clinical trial information: UMIN000004882.