A phase II trial of high-dose cetuximab (cmab) plus irinotecan in patients (pts) with KRAS wild-type (WT) metastatic colorectal cancer (MCRC) who progressed on standard-dose cmab plus irinotecan.

Abstract

598 Background: Prior clinical data suggest a dose-related response to cmab when combined with irinotecan in pts with KRAS WT tumors who do not develop grade 2 and above rash with standard cmab dosing. However, the investigation of higher doses of cmab in the setting of acquired or innate resistance to standard dose cmab has not been previously investigated. We conducted a phase II clinical trial of high-dose cmab plus irinotecan in KRAS WT pts with standard-dose cmab plus irinotecan – refractory disease to address this question. Methods: Pts with KRAS WT MCRC progressing on standard dose of cmab with irinotecan were eligible for study. Pts should have received a minimum of 6 weeks of prior standard dose cmab plus irinotecan and progressed within 4 weeks from the last dose. Cmab was administered at 500 mg/m2/week and irinotecan was administered at the same dose/schedule on which the patient previously progressed. 12-week PFS rate was the primary endpoint. Results: 8 pts were treated on study: median age 68 yrs (45-85), 5 pts were males, ECOG performance status was 1 in all 8 pts. Grade ≥ 3 toxicities consisted of hypomagnesaemia (4 pts), anemia (1 pt), leucopenia (1 pt), fatigue (1 pt), and diarrhea (1 pt). 6 pts achieved stable disease (with regression in target lesions noted in 3 pts). 12 week PFS rate is 5/8 and 18 week PFS is 4/8. 3 pts remain on study at 4.5, 5, and 8 months from enrollment. Conclusions: High-dose cmab/irinotecan is well tolerated except for hypomagnesemia. Encouraging prolonged disease stabilizations warrant further investigation of this approach in pts in KRAS WT population. Accrual is ongoing. [Table: see text]