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

BACKGROUND: Axitinib 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. METHODS: Retrospective 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. RESULTS: Ninety-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]). CONCLUSIONS: Early HbL increase during axitinib treatment combined with hBP is an independent predictive factor of PFS. These results require validation in a prospective setting.

Does substitution of brand name medications by generics differ between pharmacotherapeutic classes? A population-based cohort study in France.

PURPOSE: The purpose of this study was to measure the rate of substitution failure to generic antiepileptic drugs (AEDs) compared to two other pharmacotherapeutic classes (neuroleptics, beta-blockers). METHODS: We conducted a cohort study involving beneficiaries of the French health insurance system from January 2009 to November 2012. Substitution failure to generic drugs was estimated by the rate of switchback (i.e. from generic drug back to its branded drug). We selected the patients who had a dispensation of a branded AED for 60 days or more during the 90 days preceding the generic substitution. Cox proportional hazard regression was used to model time to switchback for antiepileptics vs. other therapeutic classes in the 90 days after generic substitution, adjusting for age, gender and polytherapy. RESULTS: The cohort included 6727 patients of whom 1947 were exposed to AEDs, 2398 to neuroleptics and 2382 to beta-blockers. The switchback rate was 62% for AEDs. AED users were more likely to switch back as compared to beta-blocker (crude hazard ratio 1.87; 95% CI 1.68-2.07 for patients under 75) or neuroleptic users. The same observation was made in patients above 75 years (crude hazard ratio 1.36; 95% CI 1.16-1.60). CONCLUSIONS: Compared to beta-blocker users, AED users were more likely to switch back to the branded drug, whereas this difference was not observed with neuroleptics. These results could reflect a poor acceptance of switching AEDs to generic compounds in France.