Correlation of immunological effects of anti-VEGF therapy with progression-free survival of advanced colorectal cancer patients
e14559 Background: The clinical efficacy of Bevacizumab (BEV) in advanced colorectal cancer (mCRC) could be related not only to its well-established effect on tumor neoangiogenesis but also to a counteraction of VEGF-mediated dendritic cell (DC) abnormalities. The addition of BEV to chemotherapy (CT) may improve the number and function of blood DCs in cancer pts. We have focused on the correlation between this effect and the clinical efficacy of a BEV-based, 1st-line treatment for mCRC. Methods: Starting from January 2007 we performed a flow cytometric analysis of PB lymphocytes and DC subsets in 53 mCRC pts who had not received prior CT for metastatic disease or for whom 6 months had elapsed since adjuvant CT (M/F: 31/22, median age: 59yrs; range 32–75; ECOG PS <2), before and every 3 courses of a BEV+CT (5-FU± CPT11± Oxaliplatin) program. Biological data of the 42 evaluable pts that received all the planned treatment were correlated to both tumor response (OR) and progression free survival (PFS). Results: During treatment, DCs and their subsets showed a progressive, significant increase in absolute number, with respect to baseline, both in responder (CR,PR,SD) (67%) and in non responder pts. This effect on the DC profile was evidenced in responder pts up to 4 weeks since the last treatment course. After therapy completion, pts with PFS > 15 months (58%) showed DC and DC1 absolute number significantly higher with respect to pts with shorter PFS (p< .02). Conclusions: The recovery of blood DCs induced by 1st- line, BEV-based therapy in mCRC pts indicates a potential additional anticancer mechanism of this drug. The improvement of DC number does not influence OR but correlates with longer PFS. This suggests that BEV can influence tumor regrowth by contributing to overcome the impairement of the host immune surveillance induced by VEGF. No significant financial relationships to disclose.