3558 Background: Anti-epidermal growth factor receptor (anti-EGFR) antibodies alone or in combination with irinotecan (Iri) can be considered standard third-line therapy for KRAS wild-type (wKRAS) unresectable colorectal cancer (UNCRC). However, some UNCRC patients (pts) cannot tolerate Iri-containing therapy. S-1, an oral fluorouracil (FU) derivative, enhances the anti-tumor effect by inhibiting dihydropyrimidine dehydrogenase activity and reducing digestive toxicity. Combination therapy with cetuximab (C-mab) may restore 5-FU resistance in 5-FU–resistant CCs. Therefore, we examined the efficacy of S-1+C-mab therapy in wKRAS UNCRC pts, who had previously received Iri, oxaliplatin (OX), and FUs. Methods: The study design was multicenter, single-arm, open-label phase II study. The major inclusion criteria were written informed consent; histologically proven CRC and clinically proven UNCRC; presence of measurable lesions; previous therapy with Iri, OX, and 5-FU; documented progressive disease after 5-FU–based chemotherapy; wKRAS tumors; age ≥ 20 years; performance status (PS) 0–1; and adequate organ function. The treatment protocol was as follows: weekly durable intravenous (DIV) C-mab administration at 400 mg/m2 (day 1) and 250 mg/m2/week (except day 1) and oral administration of 80 mg/m2/day S-1 on days 1–28 of each 42-day cycle. The primary endpoint was progression-free survival (PFS). A sample size of 39 was planned for a threshold PFS of 3.5 months and expected value of 6.0 months, with one-sided alpha of 0.05 and beta of approximately 0.2. Results: One patient was ineligible; 38 pts (PS 0/1, 32/6; 1/2/>3 prior chemotherapy regimens, 4/23/11) were enrolled from 10/2009 to 12/2010. The median PFS (central review) was 5.5 months (90% CI: 4.4 – 5.7); median overall survival (OS), 13.1 months; and the best ORR, 36.8%. The most common grade 3–4 adverse events were neutrophils, hypokalemia, rash, and dry skin. Conclusions: This study showed that S-1+C-mab may be a promising and well-tolerated treatment choice of wKRAS UNCRC, who had previously heavily treated by Iri, OX and FUs.
A Phase II Study of Panitumumab Plus Irinotecan for Metastatic Colorectal Cancer Patients with Wild KRAS Exon 2, Resistant to Fluoropyrimidine, Oxaliplatin and Irinotecan in Japanese. (OGSG1001)