Biomolecular, biochemical, and radiologic evaluation of patients on anti-VEGF treatment for mCRC.

Abstract

556 Background: K-ras mutation is a negative predictor of clinical benefit (CB) from anti-EGFR treatment in mCRC. Bevacizumab combined with chemotherapy prolongs both PFS and OS in first-line treatment of mCRC. Previously data suggested that this results are independent of K-ras status. We conducted a study to investigate the CB of Bevacizumab in treatment of mCRC according to K-ras status and to evaluate timing of response to treatment trough the correlation between tumor markers values and clinical responses. Finally we evaluated CB in patients affected by mCRC with only hepatic metastases vs patients with multiple metastasis sites. Methods: 82 patients were enrolled and underwent first-line chemotherapy with Folfiri or FolFoX and bevacizumab. Tissue samples were analyzed for DNA sequencing in order to identify K-ras mutations in codons 12 and 13. Before therapy all patients were investigated with CT scan and with a blood sample to define tumor markers values; a new evaluation of tumor markers after 2 months of chemotherapy was performed and a CT scan after 3 months. Results: An overall objective response rate (RR) of 40% and a CB of 79% were obtained, with a correlation between tumor markers values and clinical response of 89%. 49% of population presented only hepatic metastases while other 51% showed multiple metastatic sites. RR in exclusive hepatic metastatic group was 45% vs 33% multiple metastatic sites group, CB was 90% vs 66% respectively. No grade 3 or 4 bevacizumab associated toxicity was showed in patients. K-ras mutations were investigated in 75 of 82 patients. 49 patients were wild-type (wt 65%) while 26 patients were mutated (mut 35%). RR in wt group was 45% vs 35% in mut group, while CB was 82% vs 81% respectively. Correlation between tumor markers values and clinical response was 90% in wt group vs 93% in mut group. Conclusions: RR in two K-ras groups was different with an advantage in K-ras wt group, but this difference does not observe in CB. Bevacizumab provides significant RR and CB after a short time of treatment and tumor markers values could be an optimal correlative parameters of early clinical response. Bevacizumab provides significant CB in patients with only hepatic metastases vs patients with multiple metastatic sites. No significant financial relationships to disclose.