494 Background: FOLFOX4 q1w cetuximab is a standard 1st-line regimen in KRAS wt mCRC. This trial evaluated FOLFOX4 q1w cetuximab (Arm A) and FOLFOX4 q2w cetuximab (Arm B) as 1st-line therapy in KRAS wt mCRC.
METHODS: Pts with KRAS wt mCRC were randomized to q1w cetuximab (400 mg/m(2)initial dose then 250 mg/m(2)/wk) or q2w cetuximab (500 mg/m(2) every 2 wks). Both arms received FOLFOX4 (folinic acid 200 mg/m(2), then 5-FU 400 mg/m(2)bolus, then 5-FU 600mg/m(2) over 22 h on days 1 2, plus oxaliplatin 85 mg/m(2) on day 1 q2w). Primary endpoint is objective response rate (ORR) which was analyzed in a protocol specified interim analysis. Secondary efficacy endpoints are progression- free survival (PFS) and overall survival.
RESULTS: From Sep 2007 to Sep 2009, 152 pts with KRAS wt tumors (22 centers in 12 countries) were randomized and received ≥1 dose of study treatment, arm A (n%%%equ%%u) and arm B (n%%%equ%%w). Baseline characteristics were well balanced (A vs B): mean age: 57 vs 60 years, Karnofsky Performance Score (PS) 80: 15% vs 18%, PS 90: 45% vs 40%, PS 100: 40% vs 42%, male gender: 40% vs 45%, prior adjuvant or neoadjuvant therapy: 23% vs 17%, metastases at initial diagnosis: 65% vs 64%, and >2 involved organs: 24% vs 29%. Median follow up was 12 months. ORR (CR PR) was 51% in arm A and 63% in arm B, respectively, the difference between arm B and A was 12% (95% CI: -4% to 27%). Preliminary results for PFS time did not indicate relevant differences between both arms. Mature PFS results will be presented at the symposium. Based on current data, most common grade 3-4 adverse events (≥ 10% in any arm, A vs B) were neutropenia/neutrophil count decreased in 32 vs 34%, rash in 15 vs 16% and diarrhea in 7 vs 10% of the pts.
CONCLUSIONS: These data suggest that cetuximab q2w has comparable efficacy and an equivalent safety profile as q1w dosing in combination with FOLFOX4. Data collection and analysis is ongoing. [Table: see text] [Table: see text].
CONCLUSION: As shown by the significant influence of metastatic sites, some P die from their advanced systemic disease situation before they would experience cerebral progression, in part explaining the influence of systemic treatment. In other individuals however, intensified local treatment and systemic treatment appear to influence both cTTP and OS significantly, implicating a direct influence of systemic therapy on BM. This might result from an impaired blood brain barrier around metastatic sites, making sufficient tissue concentrations of cytotoxic agents possible. No significant financial relationships to disclose.
TREATMENT: Rx 375 mg/m(2) IV at day 1; concomitant therapy: Rasburicase, steroids only for anaphylaxis, intrathecal (IT) triple drug at days 1, 3 for CNS pts only. Begin of chemotherapy at day 5. Response evaluation: product of 2 perpendicular diameters of 1 - 3 index lesions/% blasts in BM/PB within 24 h prior to Rx and at day 5: responder (RP): at least 1 lesion with at least objective effect (decrease of ≥25%) and no progress (increase of ≥25 %) at other sites. Study plan: Simon 2-stage phase II with α and β = 5%. Response rate (RR) for poor activity was set to 45%, for good activity 65%. 33 pts entered the first stage, final evaluation after 79 pts.