PS2-29: KRAS Testing in Metastatic Colorectal Cancer: The CERGEN-C Comparative Effectiveness Study.

Pawloski P; on behalf of the CERGEN Study Team.

Abstract

Genetic testing to inform health professionals and patients of disease risk, diagnostic, prognostic, or treatment information such as KRAS mutation testing to determine colorectal cancer (CRC) treatment is an evolving health care approach. KRAS, a pharmacogenomic marker normally expressed in wild type form, confers a lack of response to epidermal growth factor receptor (EGFR) inhibitor treatment in metastatic CRC when mutated. Mutations occur in 30-50% of CRC cases and a gap in knowledge exists regarding the impact of KRAS testing on treatment outcomes in metastatic CRC. The CERGEN-C (Comparative Effectiveness Research in Genomics & Personalized Medicine for Colorectal Cancer) study is a collaboration of eight Cancer Research Network members and four academic partners evaluating connections between evidence synthesis and evidence generation in cancer-related genomics and personalized medicine. We are conducting a comparative effectiveness study to evaluate overall survival in patients who received KRAS testing during routine medical care compared to those who did not before and after recommendations for KRAS testing were published in mid-2008. We identified 800 members from seven integrated health care organizations diagnosed with stage III (n=200) or IV (n=600) colorectal cancer from 1/1/05-7/31/2010. To date, 293 charts have been reviewed, 224 (76%) from pre-KRAS testing recommendations (pre-) and 69 (24%) from post-KRAS testing (post-) recommendations. All cases were Stage IV and the majority of cases were Caucasian, 133 (61%) pre and 51 (76%) post. A family history of any cancer was identified in 97 (43%) pre- and 29 (42%) post- cases and KRAS testing was performed in 60/293 (20%) of cases reviewed to date, 41 (18%) pre- and 19(26%) post-, respectively. Wild type KRAS was found in 28 tested cases, 21 pre- and 7 post- cases. Of the identified wild type cases, 17 pre- and 6 post- were treated with EGFR inhibitors. Overall, EGFR inhibitors were administered in 48 cases, 42 (18%) pre- and 6 (19%) post-. EGFR inhibitor treatment began with 3rd line therapy in those tested for KRAS compared to first line in those not tested. The most common chemotherapy regimen including an EGFR inhibitor was irinotecan and cetuximab, n=25 (52%).