Sunitinib-associated hypertension and neutropenia as efficacy biomarkers in metastatic renal cell carcinoma patients

Background: Metastatic renal cell carcinoma (mRCC) prognostic models may be improved by incorporating treatment-induced toxicities. Methods: In sunitinib-treated mRCC patients (N = 770), baseline prognostic factors and treatment-induced toxicities (hypertension (systolic blood pressure >= 140mmHg), neutropenia (grade >= 2), thrombocytopenia (grade >= 2), hand-foot syndrome (grade 40), and asthenia/fatigue (grade 40)) were analysed in multivariate analyses of progression-free survival (PFS) and overall survival (OS) end points. Results: On-treatment neutropenia and hypertension were associated with longer PFS (P = 0.0276 and P<0.0001, respectively) and OS (P = 0.0014 and P<0.0001, respectively), independent of baseline prognostic factors, including International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) criteria. By 12-week landmark analysis, neutropenia was significantly associated with longer PFS and OS (P = 0.013 and P = 0.0122, respectively) and hypertension or hand-foot syndrome with longer OS (P = 0.0036 and P = 0.0218, respectively). The concordance index was 0.65 (95% CI: 0.63 - 0.67) for IMDC classification alone and 0.72 (95% CI: 0.70 - 0.74) when combined with hypertension and neutropenia. Considering hypertension and neutropenia (developing both vs neither) changed IMDC-predicted median OS in each IMDC risk group (favourable: 45.3 vs 19.5 months; intermediate: 32.5 vs 8.0 months; poor: 21.1 vs 4.8 months). Conclusions: On-treatment neutropenia and hypertension are independent biomarkers of sunitinib efficacy and may add prognostic accuracy to the IMDC model.