Prognostic value of hemoglobin level increase during axitinib treatment for metastatic renal cell carcinoma.

Abstract

580 Background: Axitinib is used after failure of first line treatment for metastatic renal cell carcinoma (mRCC). A common side effect of axitinib is the increase of hemoglobin level (HbL) during treatment with a suspected correlation with better outcome. We examined whether HbL increase during the first 3 months of axitinib treatment is associated with better prognosis. Methods: Retrospective multicenter analysis including patients with mRCC treated with axitinib for at least 3 months from 2012 to 2014 as part of the French temporary use authorization cohort. Progression-free survival (PFS) was analyzed according to the following factors: gender, International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) prognostic score at axitinib initiation, polycythemia (HbL above 16.5/18.5 g/dL or hematocrit above 56/60% for women/men), and maximum increase in HbL within the first 3 months of treatment. Results: 97 patients were analyzed (71% men; median age at diagnosis: 54.7 years [22; 80]; IMDC: 23%, 49%, and 27% in the favorable, intermediate, and poor-risk group, respectively). Patients received axitinib for a median of 8 months [3; 30]. Grade 2-3 toxicities were observed in 81% of patients. Objective response rate was 32%. The median PFS and OS were 8.9 [7.4; 9.3] and 22 [19.4; not reached] months, respectively. During the first 3 months, 81 patients (84%) experienced HbL increase with a median increase of +2.3g/dL [-1.1; 7.2] and 40 of them (51%) had an increase above this median. Eight patients (8%) presented polycythemia. In univariate analysis, significantly longer PFS was observed for men (p = 0.02), for patients who had a better IMDC prognostic score (p = 0.004), and for patients who experienced an increase of HbL ≥ 2.3 g/dL (with a median PFS of 11.7 vs. 7.4 months; p = 0.025), but not for patients with polycythemia. In a multivariate analysis, after adjustment for IMDC score (p < 0.0001) and gender (p = 0.029), an increase in HbL ≥ 2.3 g/dL was significantly associated with a longer PFS (HR = 0.57, 95%CI [0.34; 0.95]). Conclusions: HbL increase ≥ 2.3g/dL in the first 3 months of axitinib treatment was associated with longer PFS. These results require validation in a prospective trial setting.