P-278 A phase II study of cetuximab in combination with irinotecan plus S-1 as first-line treatment in patients with KRAS wild-type metastatic colorectal cancer (CIRIS study): overall survival analysis

Abstract

Introduction: The CRYSTAL study demonstrated that the addition of cetuximab (Cmab) to FOLFIRI as first-line treatment improved the clinical benefit in patients (pts) with KRAS wild-type (wt) metastatic colorectal cancer (mCRC). The FIRIS study showed the non-inferiority of irinotecan plus S-1 (IRIS) to FOLFIRI. We conducted a phase II study to evaluate the efficacy and safety of Cmab in combination with IRIS as first-line treatment in pts with KRAS wt mCRC (clinical trial information: UMIN000004580). Methods: Eligibility criteria included histologically confirmed colorectal cancer; KRAS wt; no previous chemotherapy; ECOG performance status (PS) 0-1 and adequate organ function. S-1 was administered at 80mg/m2 on days 1-14 and irinotecan at 100mg/m2 on days 1 and 15 every 28 days. Cmab was administered at a loading dose of 400mg/m2, followed by weekly infusions of 250mg/m2. The primary endpoint was response rate (RR), and the secondary endpoints were progression-free survival, overall survival, rate of tumor shrinkage and safety. The sample size calculation was carried out to reject a 37% response rate in favor of a target response rate of 60%, with a significance level of 0.05 and a statistical power of 80%. Results: Between November 2010 and January 2013, 31 pts were enrolled. One patient was ineligible with inadequate renal function. The characteristics of the pts were as follows; median age: 65.5 (range: 38-79), male/female: 20/10, ECOG PS 0/1: 24/6, colon/rectum: 22/8, unresectable/recurrent: 21/9. The RR was 70% (95% CI: 52.1-83.3%) with complete response: 2, partial response: 19, stable disease: 9 and progressive disease: 0. With a median follow-up time of 21.3 months, the median PFS and OS were 11.3 months (95% CI: 6.8-14.7 months) and 25.8 months (95% CI: 19.1-37.1 months), respectively. The most common Grade 3-4 adverse events were leukopenia (20%), neutropenia (43%), febrile neutropenia (7%), anemia (13%), hypoalbuminemia (17%), anorexia (13%), diarrhea (10%), mucositis (7%), acne-like rush (13%), dry skin (20%) and paronychia (10%). There were no treatment-related deaths. Conclusion: Cetuximab in combination with irinotecan plus S-1 as first-line treatment was considered one of the promising options and showed manageable toxicities in patients with KRAS wild-type metastatic colorectal cancer.