Prognostic value of KRAS in terms of efficacy and safety of bevacizumab as neoadjuvant or conversion treatment in patients with colorectal liver metastasis.

Abstract

e14058 Background: Patients with colorectal cancer (CRC) and liver metastases have a poor prognosis, only a small proportion has initially resectable metastases. Bevacizumab (BEV) added to chemotherapy (CT) is active for metastatic CRC. This study aimed to assess efficacy and safety of BEV as neoadjuvant or conversion treatment in patients with CRC liver metastases. Methods: Observational retrospective review in CRC patients with liver metastases who have undergone neoadjuvant or conversion CT with BEV as first or second line treatment. Results: 34 patients analyzed: 53% male; median age 55; 77% had metastases at diagnosis; ECOG 0-1 (38-62%); primary tumor location: 52% colon, 37% rectum, 11% colon/rectum; 84% had synchronic metastases; 16% initially resectable metastases 9% irresectable and 75% potentially resectable. 77% and 24% received first and second line BEV prior surgery respectively. Complete resection was achieved in 85%. All patients with initially unresectable metastases become resectable. 44% suffered post-operative complications; most frequent being abdominal and wound infection (12-9%). Complete pathologic response of liver metastases was seen in 7% and 61% reached major response. Median OS after surgery was 46 months. Disease free survival (DFS) since surgery was 8.8 months without significant differences between those receiving BEV as first or second line treatment. 88% of patients did not expeirence grade 3-4 toxicity. KRAS mutation was detected in 10 of 26 patients with available KRAS status (39%). Median DFS was significantly longer in wild type wt-KRAS patients compared with those mutated m-KRAS (12 vs 7 months p<0.001) thus confirming KRAS as a prognostic biomarker. Major pathologic response rate was significantly improved in wt-KRAS patients vs m-KRAS (84% vs 25% p<0.001). Conclusions: Neoadjuvant or conversion CT with BEV is an active treatment option for patients with CRC liver metastases with an adequate safety profile and without an apparent increase of surgical complications. While both wt-KRAS and m-KRAS patients benefit from treatment with BEV, wt-KRAS patients obtain greater pathologic response and significant longer DFS.