3580 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 600 mg/m(2) over 22 h on days 1 2, plus oxaliplatin 85 mg/m(2) on day 1 q2w). Primary endpoint was objective response rate (ORR). Secondary efficacy endpoints were disease control rate (DCR), progression free survival (PFS) and overall survival (OS).
RESULTS: 152 pts with KRAS wt tumors (22 centers in 12 countries) were randomized to arm A (n%%%equ%%u) and arm B (n%%%equ%%w). Baseline characteristics were well balanced. Median follow up for PFS analysis was 16.5 months. Overall ORR (55% vs 59%) and PFS (9.5 mo vs 9.3 mo) were similar in patients with EGFR detected and nondetectable tumors. OS data are not yet mature. Based on current data most common (≥10% in either arm) G3/4 treatment emergent adverse events were comparable in FOLFOX q1w cetuximab and FOLFOX q2w cetuximab: neutropenia/neutrophil decrease (32% vs 34%), rash (15% vs 16%), diarrhea (7% vs 10%). G3/4 composite adverse events categories specific to cetuximab or FOLFOX showed no difference between treatment arms: infusion-related reactions (2.7% vs 2.6%), skin reactions (24% vs 26%), neurotoxicities (0% vs 1.3%).
CONCLUSIONS: These data suggest that in terms of ORR, DCR, PFS and safety, cetuximab q2w is a convenient alternative to the standard q1w regimen when combined with FOLFOX4. Determination of EGFR expression status does not help to identify patients more likely to benefit from treatment. [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.