Role of KRAS mutation in advanced ovarian cancers treated by targeted medicines in Thailand.

Abstract

e22072 Background: The treatment of advanced ovarian cancer has been surgery followed by various forms of chemotherapeutic agents. Once the chemotherapeutic agents failed to achieve the response, the option left is rather diamal. Recent advances in targeted medicines along with specific genes study allowed us to study this group of patients. Our objective is to 1) to determineKRAS mutation in all ovarian cancers treated by targeted medicines 2) To compare the response of patients with KRAS mutation versus those without KRAS mutation 3) To modulate the treatment in the presence of KRAS mutation. Methods: 25 cases of advanced and recurred (stage IV) ovarian cancers who had exhausted all chemotherapeutic treatment were included in the study. To select the targetsfor the treatment, we examined the VEGF, EGFR,cKIT and HER2 genes using IHC ( Immunohistochemical) technique with additional DNA study. KRAS mutation was studied by DNA sequencing technique. Treatment targeted medicines used: 13 cases of Bevacizumab+ sunitinib, 4 cases of Bevacizumab+ EGFR TKI, 6 cases of Bevacizumab + Anti-EGFR monoclonal antibody and 2 cases of Bevacizumab+ trastuzumab. Results: 1) KRAS mutations were found in 10 of 25 cases (40%). Types of mutation included; 3 cases of G12D mutation, 4 cases of G12V mutation, 2 cases of G12C mutation and 1 case of G13D mutation. 2) Responses: Those with KRAS mutation showed 3 months response of 3/10 (30%) and those without KRAS mutation showed 3 months response of 9/15 ( 60%). For one year response: Those with KRAS mutation showed 1/10 (10%) and those without KRAS mutation showed 5/15 (33%) one year response. Conclusions: 1) Type of KRAS mutation played no role in achieving response. 2) Cases with KRAS mutation represented the overall poor prognosis. 3) At present, we have been using mTOR inhibitor in order to block PI-3K signal transduction pathway in KRAS mutation patients with some degrees of success.