Haemoglobin level increase as an efficacy biomarker during axitinib treatment for metastatic renal cell carcinoma: a retrospective study

Abstract

BackgroundAxitinib is used after failure of first line treatment for metastatic renal cell carcinoma (mRCC). A known side effect is the increase of haemoglobin level (HbL) during treatment with a suspected correlation with better outcome. Our objective was to examine whether HbL increase during the first three months of axitinib treatment is associated with better prognosis.MethodsRetrospective multicentre analysis including patients with mRCC treated with axitinib for at least three months from 2012 to 2014. Progression-free survival (PFS) was analysed by a Cox model according to gender, International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) prognostic score, high blood pressure (hBP), and maximum increase in HbL within the first three months of treatment.ResultsNinety-eight patients were analysed (71% men; median age at treatment initiation: 62 years; IMDC: 24%, 50%, and 26% in the favourable, intermediate, and poor-risk group, respectively). Patients received axitinib for a median of 8 months. During the first three months, the median increase of HbL was +2.3 g/dL (−1.1; 7.2). Fifty-six (57%) patients developed hBP.In multivariate analysis, after adjustment for performance status (P < 0.0001) and gender (P = 0.0041), the combination of HbL increase ≥2.3 g/dL and any grade hBP was significantly associated with longer PFS (HR = 0.40, 95%CI [0.24; 0.68]).ConclusionsEarly HbL increase during axitinib treatment combined with hBP is an independent predictive factor of PFS. These results require validation in a prospective setting.

Long-lasting response with polycythemia to third-line axitinib treatment in metastatic renal cell carcinoma: Very rare case presentation

“…In our case, PFS is longer than the upper limit in the other studies. 6,8 Polycythemia was the first response to treatment of axitinib in our patient. It may be an indicator of persistent treatment response.…”

“…6 In a recent retrospective study of axitinib-induced HB and blood pressure (BP), changes were reported on the combination of HB increase and any grade high BP was significantly associated with longer PFS (median PFS 14.7 months, range 10.8-19.6). 8 They did not evaluate EPO levels. The mechanism of increasing HB level with TKI therapy is not clear.…”

Cardiomyocyte crosstalk with endothelium modulates cardiac structure, function, and ischemia-reperfusion injury susceptibility through erythropoietin

“…Several independent labs show active systemic crosstalk between EPO-EPOR and VEGF-VEGFR signal transduction pathways. rhEPO increases Vegf expression ( Ribatti et al, 1999 ; Westenbrink et al, 2008 ; Lu et al, 2012 ; Oztas et al, 2020 ) resulting in angiogenesis and attenuated interstitial fibrosis, while VEGF-VEGFR blockade induces non-renal Epo expression ( Tam et al, 2006 ) and erythropoiesis ( Tam et al, 2006 ; Johnson et al, 2017 ). Whether these pathways interact similarly in the heart by endogenous forms of EPO and VEGF, is unknown.…”

Neuron-Specific Enolase and Hemoglobin as Risk Factors of Intraocular Metastasis in Patients with Renal Cell Carcinoma

“…Indeed, previous research has shown that mRCC patients receiving treatment with tyrosine kinase inhibitors, who exhibit increased levels of Hb, were linked to longer OS and progression-free survival [ 45 ]. Furthermore, mRCC patients showing an early increase in the levels of Hb during treatment with axitinib have been related to an obvious improvement in clinical outcome [ 46 ]. The occurrence of anemia in patients with ccRCC increases the risk of death by causes other than RCC [ 47 ].…”