A Phase II Study of Cetuximab Plus Irinotecan/S-1 as First-Line Treatment in KRAS Wild-Type Metastatic Colorectal Cancer

Abstract

Background: 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). Because the FIRIS study demonstrated the non-inferiority of irinotecan plus S-1 (IRIS) to FOLFIRI for mCRC, 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 (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 80 mg/m2 on days 1-14 and irinotecan at 100 mg/m2 on days 1 and 15 every 28days. Cmab was administered at a loading dose of 400 mg/ m2, followed by weekly infusions of 250 mg/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%. Result: 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 most common grade 3-4 adverse events were leukopenia (22.6%), neutropenia (41.9%), febrile neutropenia (9.7%), anemia (9.7%), hypoalbuminemia (12.9%), anorexia (16.1%), diarrhea (9.7%), mucositis (9.7%), acne-like rush (9.7%), dry skin (19.4%) and paronychia (9.7%). There were no treatment-related deaths. Conclusion: Cmab in combination with IRIS showed manageable toxicities in pts with KRAS wt mCRC. The result of the efficacy will be presented at the meeting.