Associations between the EGFR status as well as KRAS mutations and clinical outcome in colorectal cancer (CRC) patients (pts) treated with erlotinib monotherapy in 2 or 3 line-A study of the Arbeitsgemeinschaft Internistische.

14574 Background: Genetic aberrations within the EGFR pathway including KRAS mutations and polymorphisms of EGFR have been demonstrated to be associated with response to EGFR inhibitors like cetuximab and panitumumab in CRC. Here, we investigated whether these genetic changes may impact response and survival in CRC patients treated with erlotinib monotherapy.,Within a multicenter phase II trialCRC patients who failed 2 0r 3 previous chemotherapies with 5-FU, irinotecan or oxaliplatin were treated with erlotinib monotherapy (150 mg/day p.o.) until disease progression. Response was evaluated every 8 weeks according to RECIST criteria. Analyses of the EGFR pathway including KRAS-mutations, EGFR polymorphisms (CA repeat intron 1, HER-497, EGFR-216G>T, - 191C>A), EGFR gene amplification and protein expression were performed in 38 pts. Analyses were carried out following microdissection of the tumor.,Patients possessing the HER-497 Lys/Lys genotype demonstrated a significantly improved median progression- free survival with 4.7 months compared to 1.8 months in Arg/Lys and in Arg/Arg patients (p=0.03, Chi-square test). Patients homozygous for the EGFR-216 T/T genotype demonstrated inferior median PFS with 0.85 months compared to 1.87 and 1,84 months in patients showing a G/G or G/T genotype, respectively (p<0.001, Chi-square test). KRAS mutations (codon 12, 13) were detected in 9/31 (29%) pts. Disease control at 8 weeks was seen in 41% of pts with KRAS wild-type (9/22) compared to only 22% of pts with KRAS mutation(2/9) (p=0.4). No associations between PFS or tumor control and EGFR FISH or expression analyses were detected. Associations with overall survival will be demonstrated at the meeting.,EGFRpolymorphisms (HER-497, EGFR-216) may be associated with progession-free survival of CRC patients treated with erlotinib monotherapy in 2 or 3 line. To our knowledge this is the first report demonstrating a relationship between EGFR polymorphism and erlotinib in CRC. The role of EGFR polymorphism and KRAS mutations for erlotinib therapy in CRC warrants further investigation in larger trials. [Table: see text].