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...

Date 04 July 2015
Event WorldGI 2015
Session Posters
Topics Anticancer Agents
Colon and Rectal Cancer
Translational Research
Basic Principles in the Management and Treatment (of cancer)
Biological Therapy
Presenter T. Eto
Citation Annals of Oncology (2015) 26 (suppl_4): 1-100. 10.1093/annonc/mdv233
Authors T. Eto1, K. Suzuki1, T. Masuishi2, T. Matsui1, S. Anzai1, Y. Suzuki1, Y. Fukami1, F. Kusano1, Y. Sakai1, J. Tazawa1
  • 1Tsuchiura Kyodo General Hospital, Tsuchiura/JP
  • 2Aichi Cancer Center Hospital, Nagoya/JP



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).


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%.


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.


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.