Activity and tolerance of biweekly CapeOx-cetuximab in 1st line therapy of metastatic colorectal cancer (mCRC): Relation to K-ras mutation status

Abstract

e15018 Background: This novel q2w schedule trial combined oxaliplatin (Ox), flat dose capecitabine (Cape) and cetuximab(C) in first line therapy of mCRC. C was given weekly initially and then q2w. We report the response rate, toxicity and influence of K-ras mutation status in first-line patients treated with biweekly CapeOx-C in this phase II trial. Methods: Pts with previously untreated, histologically confirmed, metastatic colon adenocarcinoma, ECOG PS 0–1, and adequate organ function were eligible. Pts were treated with C (initially 250mg/m2 q week and later amended to 500mg/m2 q2w) and Ox (85mg/m2) combined with flat dose Cape (2500mg po bid x 7days) q2w. Endpoints included response (RECIST), toxicity (CTCAE v3) and relationship to K-ras mutation status as determined in codons 12/13 of exon 2 in genomic tumor DNA by PCR, blinded to clinical data. Results: Between 8/04 and 8/08, 27 pts were enrolled. One pt failed screening, 1 withdrew prior to rx and 2 too early for assessment. 25 pts were treated: M/F (15/10), PS 0/1 (13/12), median age 65 yrs (37–80). 12 pts were treated weekly with C and 13 q2w. 23 pts were eligible for both toxicity and efficacy analysis. The most common grade 3/4 toxicities (N=23) were diarrhea (26%), thrombosis (22%), neuropathy (17%), rash (13%), hand-foot syndrome (9%), hypersensitivity reaction (9%), stomatitis (9%). Toxicity profiles between the two C schedules were comparable. Of 23 pts evaluable for response, there were 2 CR, 12 PR, and 3 SD (ORR 61%; disease control rate (DCR) 74%). K-ras status was determined in 18 pts: 9 were K-ras wild-type (WT) and 9 mutant (MT) with ORR and DCR = 66%, 89% for WT vs. 44%, 44% MT. Time on study was 6 mon for WT vs 3 mon for MT (p<0.05). Grade 0–1 vs. 2–3 skin rash was 33% vs. 67% for WT and. 89% vs. 11% in MT pts. Conclusions: The novel combination of biweekly CapeOx-C, with flat dose Cape was well tolerated and very active (regardless of K-ras status) as first line treatment in mCRC. C 500 mg/m2 q2w appears equal to weekly dosing. Analysis of the K-ras mutation status showed a trend toward increased benefit by response rate and time on study, with more cutaneous toxicity in K-ras WT pts. [Supported in part by grant from BMS.] [Table: see text]