Biomarker potential of EGFR gene copy number by FISH in the phase III EXTREME study: Platinum-based CT plus cetuximab in first-line R/M SCCHN

Abstract

6005 Background: Platinum-based CT + cetuximab is the first systemic therapy in ∼30 years to show a survival benefit vs platinum-based CT in first-line R/M SCCHN (Vermorken JB, et al. N Engl J Med 2008;359:1116–1127). A retrospective analysis has evaluated the influence of EGFR gene copy number, determined by FISH, on clinical outcome in the EXTREME study. Methods: Pts were randomized to 3-weekly cycles of platinum-based CT (cisplatin 100 mg/m2 or carboplatin AUC 5, day 1; 5-fluorouracil 1000 mg/m2/day continuous infusion, days 1–4) with or without cetuximab (initial dose 400 mg/m2, then 250 mg/m2 weekly). The proportion of FISH+ cells per pt (FISH score) was determined using 5 different enrichment models. Tumors were also classified as FISH+ or FISH- using the Colorado scoring system. Results: In the overall population (n=442), addition of cetuximab significantly improved median OS (10.1 vs 7.4 months; p=0.04). No association between FISH score and OS, PFS, or best overall response was determined for any enrichment model. Pts with Colorado FISH+ tumors were evenly distributed between the CT + cetuximab (50/158) and CT-alone (51/154) arms of the FISH- evaluable population (71% of ITT population). Colorado FISH status had no influence on OS in either treatment arm, on PFS in the CT-alone arm, or on RR in the CT + cetuximab arm (see table ). In the CT + cetuximab arm, pts with FISH+ tumors had a lower risk of progression than pts with FISH- tumors. Higher RRs among pts with FISH- tumors in the CT-alone arm may have been due to twice as many nonevaluable response observations in the FISH+ vs the FISH- population (percentage of pts with SD or PD was comparable). Conclusions: EGFR gene copy number, as determined by FISH, is not a predictive biomarker for cetuximab efficacy in R/M SCCHN. [Table: see text] [Table: see text]