Decrease of Pro-Angiogenic Monocytes Predicts Clinical Response to Anti-Angiogenic Treatment in Patients with Metastatic Renal Cell Carcinoma
Stéphane Oudard, Nadine Benhamouda, Bernard Escudier, Patrice Ravel, Thi Tran, Émeline Levionnois, Sylvie Négrier, Philippe Barthélémy, Jean François Berdah, Marine Gross‐Goupil, Cora N. Sternberg, Petri Bono, Camillo Porta, Ugo De Giorgi, Omi Parikh, Robert D. Hawkins, Martin Highley, Jochen Wilke, Thomas Decker, Corinne Tanchot, Alain Gey, Magali Terme, Éric Tartour
Abstract
The modulation of subpopulations of pro-angiogenic monocytes (VEGFR-1+CD14 and Tie2+CD14) was analyzed in an ancillary study from the prospective PazopanIb versus Sunitinib patient preferenCE Study (PISCES) (NCT01064310), where metastatic renal cell carcinoma (mRCC) patients were treated with two anti-angiogenic drugs, either sunitinib or pazopanib. Blood samples from 86 patients were collected prospectively at baseline (T1), and at 10 weeks (T2) and 20 weeks (T3) after starting anti-angiogenic therapy. Various subpopulations of myeloid cells (monocytes, VEGFR-1+CD14 and Tie2+CD14 cells) decreased during treatment. When patients were divided into two subgroups with a decrease (defined as a >20% reduction from baseline value) (group 1) or not (group 2) at T3 for VEGFR-1+CD14 cells, group 1 patients presented a median PFS and OS of 24 months and 37 months, respectively, compared with a median PFS of 9 months (p = 0.032) and a median OS of 16 months (p = 0.033) in group 2 patients. The reduction in Tie2+CD14 at T3 predicted a benefit in OS at 18 months after therapy (p = 0.04). In conclusion, in this prospective clinical trial, a significant decrease in subpopulations of pro-angiogenic monocytes was associated with clinical response to anti-angiogenic drugs in patients with mRCC.