Impact of EGFR and KRAS genotype on outcomes in a clinical trial registry of NSCLC patients initially treated with erlotinib or gefitinib.

8035 Background: There is increasing interest in the impact of EGFR and KRAS genotype on patterns of response and resistance NSCLC pts treated with gefitinib or erlotinib. We created a mutation registry to track protocol-based clinical outcomes with specific mutations in NSCLC pts initially treated with an EGFR-TKI.,To date, 5 clinical trials performed in the US and Europe have been included in this registry. These include: 1) erlotinib in pts age > 70 yrs; 2) erlotinib in unselected NSCLC pts; 3) gefitinib in pts with known EGFR mutations; 4) erlotinib in pts with bronchioloalveolar carcinoma (BAC) or adenocarcinoma with BAC features; and 5) erlotinib for women with adenocarcinoma who were former or never smokers. The registry includes only chemo-naïve pts, to assess the impact of EGFR-TKI's on tumors that have not been exposed to the effects of cytotoxic chemotherapy.,290 previously untreated pts have been enrolled and treated in these 5 trials from 2003 until the present. 277 chemo-naive pts were tested for EGFR mutations, and 180 were tested for KRAS mutations. A total of 121 mutations in EGFR or KRAS were detected. 75 pts had a sensitizing EGFR mutation. (RR = 63%, median PFS=11.4 m, median OS=23.8 m). Pts with exon 19 deletions had prolonged median TTP (13.0 vs 9.7 m) and median OS (30.8 vs 14.8 m) compared with pts with an L858R mutation. In the 75 pts found to have sensitizing EGFR mutations, there was no correlation between clinical outcomes and either smoking status, gender, or the type of EGFR-TKI administered (erlotinib vs gefitinib). KRAS mutations, EGFR exon 20 insertions, and T790M mutations were associated with resistance to EGFR-TKI therapy. There were no clinical responses in this group. For 40 pts with KRAS mutations alone, median progression-free survival was only 3.3 months; overall survival was 13.0 months.,EGFR and KRAS genotype have an important impact on predicting clinical outcomes to treatment with an EGFR-TKI. The creation of a central genotype registry may help to yield more powerful insight into roles of these and other specific mutations and help guide treatment decisions. [Table: see text].